Search "Windows 95 Start Button" (2024)

CloseLevonorgestrel intrauterine device: Drug informationLevonorgestrel intrauterine device: Drug information(For additional information see "Levonorgestrel intrauterine device: Patient drug information" and see "Levonorgestrel intrauterine device: Pediatric drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USKyleena;Liletta (52 MG);Mirena (52 MG);SkylaBrand Names: CanadaKyleena;MirenaPharmacologic CategoryContraceptive;ProgestinDosing: AdultAbnormal uterine bleeding, nonacuteAbnormal uterine bleeding, nonacute (52 mg devices: Mirena, Liletta [off-label use]): Note: Not indicated for management of acute abnormal bleeding (ie, excessively heavy or prolonged bleeding that requires urgent evaluation).Initiation of therapy: For patients not currently using a hormonal contraceptive or intrauterine contraception, insert the IUD into the uterine cavity at any time during the menstrual cycle once it is determined that the patient is not pregnant. Back-up contraception is not needed if insertion is within 7 days of onset of menstruation. If insertion occurs >7 days after onset of menses, use a barrier method of contraception for 7 days.Continuation of therapy: Menstrual suppression may attenuate prior to recommended durations for contraception, requiring more frequent replacement of the device (Kaunitz 2012). When it is time to replace IUD, remove and replace with a new device immediately, or at any time during menstrual cycle as follows, provided the patient is not pregnant:Mirena: In general, replace by the end of 5 years for nonacute abnormal uterine bleeding. Initially releases levonorgestrel 21 mcg/day, then rate subsequently decreases to ~11 mcg/day after 5 years and to 7 mcg/day after 8 years. If bleeding is controlled and contraception is still desired, may leave in place for up to 8 years.Liletta (off-label use): Duration of therapy not clearly established for nonacute abnormal uterine bleeding (Kaunitz 2012). Initially releases levonorgestrel 20 mcg/day, then rate subsequently decreases to ~6.5 mcg/day after 8 years. If bleeding is controlled and contraception is still desired, may leave in place up to 8 years.Note: For instruction on switching from a different contraceptive and use after childbirth, abortion, or miscarriage, refer to dosing for "Contraception."ContraceptionContraception:Initiation of therapy: In patients not currently using a hormonal contraceptive or intrauterine contraception, insert IUD into the uterine cavity at any time during the menstrual cycle once it is determined that the patient is not pregnant. Back-up contraception is not needed if insertion is within 7 days of onset of menstruation. If insertion occurs >7 days after menstrual bleeding started, use a barrier method of contraception for 7 days unless the patient abstains from sexual intercourse.Continuation of therapy: When it is time to replace IUD, remove and replace immediately or at any time during menstrual cycle as follows, as long as the patient is not pregnant:Kyleena: Replace by the end of 5 years. Initially releases levonorgestrel ~17.5 mcg/day after 24 days, then rate subsequently decreases; the average release rate over 5 years is levonorgestrel ~9 mcg/day. Do not leave device in place for >5 years.Liletta: Replace by the end of 8 years. Initially releases levonorgestrel ~20 mcg/day, then rate subsequently decreases; the average release rate over 8 years is levonorgestrel ~13.5 mcg/day. Do not leave in place for >8 years.Mirena: Replace by the end of 8 years. Initially releases levonorgestrel 21 mcg/day, then rate subsequently decreases to ~11 mcg/day after 5 years and 7 mcg/day after 8 years. Do not leave device in place for >8 years.Skyla, Jaydess [Canadian product]: Replace by the end of 3 years. Initially releases levonorgestrel ~14 mcg/day after 24 days, then rate subsequently decreases; mean release rate over 3 years is levonorgestrel ~6 mcg/day. Do not leave device in place for >3 years.Patients Switching from a Different Contraceptive to Levonorgestrel IUDCurrent methodInstructions for switching to levonorgestrel IUDa When switching from a copper IUD, if sexual intercourse occurred after the start of the current cycle, and it has been >5 days since bleeding began, consider administering an emergency contraceptive (CDC [Curtis 2016a]).Hormonal contraceptive (oral, transdermal, vagin*l)Insert levonorgestrel IUD at any time, including hormone-free interval of the previous method. If inserted during active use of the previous method, continue previous method for 7 days after insertion or until the end of the current treatment cycle.If using continuous hormonal contraception, continue previous method for 7 days after insertion.Injectable progestinInsert levonorgestrel IUD at any time. If inserted >13 weeks after the last injection, use a barrier method of contraception for 7 days.Implant or another intrauterine system (IUS)aInsert levonorgestrel IUD on the same day the implant or IUS is removed, any time during the menstrual cycle.Switching from levonorgestrel IUD to a different contraceptive: If the patient wishes to change to a different method of birth control, remove IUD during the first 7 days of menstrual cycle and begin the new therapy. If the IUD is not removed during the first 7 days of menstruation (or if the patient has irregular menstrual cycles or amenorrhea), start the new method at least 7 days prior to IUD removal, otherwise, use a back-up barrier contraceptive for 7 days after the IUD is removed, unless the patient abstains from vagin*l intercourse.Use of Levonorgestrel IUD After Childbirth, Abortion, or Miscarriagea Product labeling recommends insertion following removal of the placenta, or waiting at least 6 weeks following delivery, or until the uterus is fully involuted. According to evidence-based guidelines, insertion postpartum (immediate insertion within 10 minutes of placental delivery or interval insertion during the 6-week postpartum period) or following an abortion are safe despite a higher risk of expulsion immediately postpartum or following a second trimester abortion and may be offered regardless of breastfeeding status to help prevent rapid repeat and unintended pregnancies (ACOG 2017; CDC [Curtis 2016b]).b Back up contraception is needed for 7 days unless IUD is placed at the time of surgical abortion. Do not administer immediately following a septic abortion (CDC [Curtis 2016a]).Use after childbirth (immediate)Insert levonorgestrel IUD after removal of the placenta; backup contraception is not needed.aUse after childbirth (interval insertion following complete involution of the uterus)Do not insert levonorgestrel IUD <6 weeks after childbirth or if the uterus is not fully involuted.aInsert at any time if it is determined that the patient is not pregnant. If menstruation has not yet resumed, consider the possibility of ovulation and conception occurring prior to IUD insertion.Back-up contraception is not needed if insertion is within 7 days of onset of menstruation. If insertion occurs >7 days after menstrual bleeding started, use a barrier method of contraception for 7 days unless the patient abstains from sexual intercourse.The risk of perforation is increased in lactating patients.Use after first trimester abortion or miscarriagebInsert levonorgestrel IUD immediately after a first-trimester abortion or miscarriage.Use after second trimester abortion or miscarriagebRefer to instructions for use after childbirth.DysmenorrheaDysmenorrhea (off-label use): 52 mg device: Refer to dosing for "Contraception" (ACOG 2018).Endometrial hyperplasia, treatmentEndometrial hyperplasia, treatment (off-label use): 52 mg device: Insert into the intrauterine cavity for hyperplasia without atypia or atypical endometrial hyperplasia/endometrial intraepithelial neoplasia. IUDs that contain levonorgestrel 52 mg in a reservoir initially release ~20 mcg/day then progressively decrease to ~10 mcg/day after 5 years. Replace after 5 years; however, the optimal duration of treatment is not known (ACOG 2015; Armstrong 2012; Orbo 2014; Trimble 2012).Estrogen therapy-associated endometrial hyperplasia, preventionEstrogen therapy-associated endometrial hyperplasia, prevention (off-label use) (alternative agent):Note: Based on data in patients who are peri- and postmenopausal; may be considered as an alternative for prevention of endometrial hyperplasia in patients with a uterus receiving estrogen therapy (eg, for vasomotor symptoms associated with menopause or secondary amenorrhea) but who are unable to tolerate oral progestogen (ie, a natural progesterone or synthetic progestin) regimens, particularly if patients desire or need contraception and/or treatment for heavy menstrual bleeding (Somboonp*rn 2011; Varila 2001; Wildemeersch 2005; Wildemeersch 2007).All devices: Confirm no possibility of pregnancy. Insert into the intrauterine cavity. In patients with menstrual cycles, may insert at any time. Discontinue when estrogen therapy is discontinued, unless also being used for contraception. Refer also to dosing for “Contraception.” Note: Limited data are available with an IUD that released LNG-20 mcg/day for up to 5 years; however, LNG-14 mcg/day for up to 3 years has also been studied (Somboonp*rn 2011; Varila 2001; Wildemeersch 2005; Wildemeersch 2007).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultThere are no dosage adjustments provided in the manufacturer's labeling (has not been studied).Dosing: Hepatic Impairment: AdultThere are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use of the intrauterine device is contraindicated with active hepatic disease or hepatic tumor.Dosing: Pediatric(For additional information see "Levonorgestrel intrauterine device: Pediatric drug information")Contraception or heavy menstrual bleedingContraception (Kyleena, Liletta, Mirena, Skyla, Jaydess) or heavy menstrual bleeding (Mirena):Postmenarche patients: Intrauterine device (IUD):Initiation of therapy: In patients not currently using a hormonal contraceptive or intrauterine contraception, the IUD may be inserted into the uterine cavity at any time during the menstrual cycle once it is determined that the patient is not pregnant. Backup contraception is not needed if insertion is within 7 days of onset of menstruation. If insertion occurs >7 days after menstrual bleeding started, a barrier method of contraception must be used for 7 days unless the patient abstains from sexual intercourse.Continuation of therapy: Duration of action is product-specific. When it is time to replace, the dated IUD is removed and replaced as follows with a new device immediately, and at any time during menstrual cycle as long as the patient is not pregnant:Kyleena: Replace by the end of 5 years. Initially releases levonorgestrel ~17.5 mcg/day after 24 days, then rate subsequently decreases; the average release rate over 5 years is levonorgestrel ~9 mcg/day. Do not leave device in place for >5 years.Liletta: Replace by the end of 6 years. Initially releases levonorgestrel 20 mcg/day, then rate subsequently decreases; the average release rate over 6 years is levonorgestrel ~14.3 mcg/day. Do not leave in place for >6 years.Mirena: Replace by the end of 8 years. Initially releases levonorgestrel 21 mcg/day, then rate subsequently decreases to ~11 mcg/day after 5 years and 7 mcg/day after 8 years. Do not leave device in place for >8 years.Skyla, Jaydess [Canadian product]: Replace by the end of 3 years. Initially releases levonorgestrel ~14 mcg/day after 24 days, then rate subsequently decreases; mean release rate over 3 years is levonorgestrel ~6 mcg/day. Do not leave device in place for >3 years.Patients Switching from a Different Contraceptive to Levonorgestrel IUDCurrent MethodInstructions for Switching to Levonorgestrel IUDa When switching from a copper IUD, if sexual intercourse occurred after the start of the current cycle, and it has been >5 days since bleeding began, consider administering an emergency contraceptive (CDC [Curtis 2016a]).Hormonal contraceptive (oral, transdermal, vagin*l)Levonorgestrel IUD may be inserted anytime, including hormone-free interval of the previous method. If inserted during active use of the previous method, continue previous method for 7 days after insertion or until the end of the current treatment cycle.If using continuous hormonal contraception, continue previous method for 7 days after insertion.Injectable progestinLevonorgestrel IUD may be inserted at any time. If inserted >13 weeks after the last injection, a barrier method of contraception should also be used for 7 days.Implant or another intrauterine system (IUS)aLevonorgestrel IUD may be inserted on the same day the implant or IUS is removed, any time during the menstrual cycle.Switching from levonorgestrel IUD to a different contraceptive: If the patient wishes to change to a different method of birth control, may remove the device during the first 7 days of menstrual cycle and begin the new therapy. If the device is not removed during the first 7 days of menstruation (or if the patient has irregular menstrual cycles or amenorrhea) and wants to start a different method of birth control, start the new method at least 7 days prior to device removal, otherwise, a backup barrier contraceptive should be used for 7 days after the device is removed unless the patient abstains from vagin*l intercourse.Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricThere are no dosage adjustments provided in the manufacturer's labeling (has not been studied).Dosing: Hepatic Impairment: PediatricPostmenarche patients: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use of the intrauterine device is contraindicated with active hepatic disease or hepatic tumor.Dosing: Older AdultNot indicated for use in patients who are postmenopausal.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Intrauterine Device, Intrauterine: Kyleena: 19.5 mgLiletta (52 MG): 20.1 mcg/dayMirena (52 MG): 20 mcg/daySkyla: 13.5 mgGeneric Equivalent Available: USNoDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Intrauterine Device, Intrauterine: Kyleena: 19.5 mgMirena: 52 mgAdministration: AdultTo be inserted into the uterine cavity. Consider administering analgesics or cervical anesthetic prior to insertion. Insert into the uterine cavity to the recommended depth with the provided insertion device; do not force into the uterus. If necessary, dilate the cervical canal and consider using a paracervical block. Transvagin*l ultrasound may be used to check proper placement. Remove if not positioned properly and insert a new IUD; do not reinsert removed IUD. Exclude uterine perforation if exceptional pain or bleeding occurs after insertion. Ensure device is intact after removal. Check expiration of IUD prior to insertion. Use of the provided inserter and directions for insertion are different for immediate insertion after childbirth or second-trimester abortion, or miscarriage. Refer to manufacturer's labeling for additional administration instructions.Because testosterone may cause vagin*l atrophy, consider pretreating with vagin*l estrogen for 2 weeks prior to insertion to patients on gender-affirming testosterone therapy (Bonnington 2020).Dysmenorrhea (off-label use): 52 mg device: Consider placing IUD during diagnostic laparoscopy to minimize pain of insertion for patients undergoing this procedure (ACOG 2018).In case of breakage or embedment of IUD in the myometrium, analgesia, paracervical anesthesia, cervical dilation, alligator forceps, or hysteroscopy may be used to aid in removal.Administration: PediatricIntrauterine device (IUD): To be inserted into the uterine cavity by a health care professional. Consider administering analgesics or cervical anesthetic prior to insertion. Insert into the uterine cavity to the recommended depth with the provided insertion device; should not be forced into the uterus. If necessary, dilate the cervical canal and consider using a paracervical block. Transvagin*l ultrasound may be used to check proper placement. Remove if not positioned properly and insert a new IUD; do not reinsert removed IUD. Exclude uterine perforation if exceptional pain or bleeding occurs after insertion. Ensure device is intact after removal. Check expiration of IUD prior to insertion. Refer to manufacturer's labeling for additional administration instructions. For patients on gender-affirming testosterone therapy, consider pretreating with vagin*l estrogen for 2 weeks prior to insertion because testosterone may cause vagin*l atrophy (Bonnington 2020). In case of breakage or embedment of IUD in the myometrium, analgesia, paracervical anesthesia, cervical dilation, alligator forceps, or hysteroscopy may be used to aid in removal.Hazardous Drugs Handling ConsiderationsHazardous agent (NIOSH 2016 [group 2]).Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. Double gloving and a protective gown are recommended for administration (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).Use: Labeled IndicationsAbnormal uterine bleeding, nonacute (52 mg devices: Mirena, Liletta [off-label use]): Treatment of abnormal uterine bleeding (ie, heavy menstrual bleeding) in patients who also choose to use an IUD for contraception.Contraception: Prevention of pregnancy (up to 3 years [Skyla], 5 years [Kyleena], or 8 years [Liletta, Mirena]).Limitations of use: For use in patients who may become pregnant; not for use prior to menarche or post menopause.Use: Off-Label: AdultDysmenorrhea; Emergency contraception; Endometrial hyperplasia, treatment; Estrogen therapy-associated endometrial hyperplasia, prevention; Menstrual suppressionMedication Safety IssuesHigh alert medication:The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.Adverse Reactions (Significant): ConsiderationsBleeding irregularitiesLevonorgestrel intrauterine device (IUD) is associated with changes in gynecological bleeding patterns, including increased number of bleeding/spotting days, irregular bleeding patterns, oligomenorrhea, and amenorrhea. Rates of frequent or prolonged bleeding rapidly decline with continued use (Ref). Menstrual blood loss can decrease by 96% after 1 year of use (Ref). Approximately 20% of women will continue to experience bleeding irregularities with continued use (Ref). Bleeding irregularities have been associated with dissatisfaction and discontinuation in some users (Ref).Mechanism: Dose-related; in addition to impacting ovulation, bleeding irregularities may be due to changes in the endometrium due to sustained progestogen exposure, decrease in steroid hormone receptors, and lack of local estrogen exposure (Ref).Onset: Varied; the first 3 to 6 months of use are generally most associated with bleeding irregularities (Ref). Twenty-six percent of users reported frequent bleeding in the first 90 days of use versus <10% in the subsequent 90 days (Ref).Risk factors:• Products containing higher doses of levonorgestrel are associated with more amenorrhea (Ref)• Self-reported duration of menstrual flow of <7 days is predictive of amenorrhea at 12 months (Ref)• Duration of menses <5 days and absence of heavy menstrual bleeding at baseline is predicative of oligomenorrhea at 12 months (Ref)Device expulsionDevice expulsion is the passage of the intrauterine device (IUD) either partially or completely through the external cervical os (Ref). Expulsion may be asymptomatic and discovered by a patient when the threads are shorter than normal, uneven, or can no longer be felt (Ref). Expulsion may also be associated with pain, bleeding, or a change in bleeding patterns (such as increased bleeding) (Ref).Onset: Varied; highest rate of expulsion is during the first year after placement of device (Ref).Risk factors: • Immediate/early (<4 weeks) postpartum placement (Ref)• Immediate postabortion placement (Ref)• Insertion into uterus <5.5 cm• Insertion into uterus not completely involuted at the time of insertion• Parous females (Ref)• vagin*l delivery (Ref)• Not breastfeeding at time of insertionEctopic pregnancyRates of ectopic pregnancy (EP) with levonorgestrel intrauterine device (IUD) use are rare and lower than the general population with estimated incidence of 0.02 to 0.2 per 100 patient-years (Ref). However, 25% to 50% of pregnancies that occur while a device is in place are likely to be ectopic with an associated risk of rupture and high morbidity (fertility loss, pregnancy loss, septic abortion) and mortality (Ref).Mechanism: Unknown; increased EP risk may be due to failure of the device (Ref). Progesterone may facilitate ciliary dysfunction and impair smooth muscle contraction within the fallopian tube, resulting in tubal retention and subsequent implantation (Ref). If the device migrates, an inflammatory reaction may occur, interfering with tubal function (Ref).Onset: Varied; risk may be higher during the first year of use (Ref); however, presentation has occurred after various durations of therapy (Ref). Case reports describe diagnosis after several days of vagin*l bleeding, vomiting, lower abdominal pain, loose stools, and abdominal fullness worsening over several days (Ref).Risk factors:• Lower IUD dose (Ref)• First year of use (Ref)• Device migration; however, in one case report, EP occurred with a correctly positioned device (Ref)• Leaving device in place longer than indicated (Ref)• History of EP• Tubal surgery• Pelvic infectionPerforation/embedded devicePenetration or embedment into the uterine wall or cervix is uncommon but is an important risk to consider with intrauterine device (IUD) use (Ref). Data from the FDA mandated study APEX-IUD (Association of Uterine Perforation and Expulsion of Intrauterine Device Study) approximates the risk at 1 to 2 perforations per 1,000 insertions (Ref). Uterine perforation may be asymptomatic and not discovered for months or years after insertion (Ref). Perforation may reduce contraceptive efficacy and result in pregnancy. Delayed detection or removal in cases of perforation may result in migration of IUD outside of uterine cavity, adhesions, peritonitis, intestinal perforations, intestinal obstruction, abscesses, and erosion of adjacent viscera.Mechanism: Complete perforation generally occurs during insertion when the IUD is forced into or through the uterine wall infiltrating all uterine layers (endometrium, myometrium, and serosa) (Ref). Partial perforation or embedment is less common but takes place when the IUD penetrates the uterine wall and remains in the myometrium (Ref). While most perforations occur during insertion, secondary perforations/embedment may occur via gradual erosion through the myometrium (Ref). Hence, a partial perforation may eventually become a complete perforation (Ref). Uterine contractions may be a factor contributing to perforations and transmural migration (Ref).Onset: Varied; most cases are not recognized at the time of insertion. Discovery of penetration/embedment may be months to years after insertion of IUD (Ref).Risk factors: • Postpartum placement up to 36 weeks (Ref)• Insertion into uterus <5.5 cm• Insertion into uterus when fixed, retroverted, or not completely involuted (Ref)• Breastfeeding at time of insertion (Ref)• Amenorrheic at time of insertion (Ref)• Insertion by a less experienced clinician (Ref)• Lower parity (Ref)• Higher number of previous abortions (Ref)• Altered myometrial integrity (eg, postmenopausal, prolonged concurrent steroid use) (Ref)Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adolescents and adults.>10%:Dermatologic: Acne vulgaris (7% to 15%)Endocrine & metabolic: Amenorrhea (≤40%; increases with duration of treatment)Gastrointestinal: Abdominal pain (≤23%)Genitourinary: Bacterial vaginosis (19%), gynecological bleeding (including decreased, increased, heavy, irregular, prolonged, unscheduled, frequent and infrequent uterine bleeding), ovarian cyst (5% to 22%), pelvic pain (≤23%), vagin*l discharge (4% to 15%), vagin*l mycosis (19%), vulvovaginitis (11% to 24%)Nervous system: Headache (≤16%), migraine (≤16%)1% to 10%:Dermatologic: Alopecia (1%), seborrhea (1% to 2%)Endocrine & metabolic: Hirsutism (<5%), weight gain (6%)Gastrointestinal: Abdominal distress, nausea, vomitingGenitourinary: Bacterial reproductive infection (1% to 4%), breast tenderness (including discomfort: ≤10%), dysmenorrhea (6% to 9%), dyspareunia (9%), endometritis (≤2%), female birth control expulsion from genital tract (3% to 5%; partial and complete), mastalgia (≤10%), pelvic inflammatory disease (<5%), uterine spasm (2%)Nervous system: Anxiety (9%), depressed mood (≤6%), depression (≤8%), mood changes (6%)Neuromuscular & skeletal: Back pain (6% to 8%)<1%: Genitourinary: Ectopic pregnancy, uterine perforationPostmarketing:Cardiovascular: Arterial thromboembolism, deep vein thrombosis, increased blood pressure, pulmonary embolismHematologic & oncologic: Malignant neoplasm of breastHypersensitivity: AngioedemaInfection: Sepsis (including Group A streptococcal sepsis) (Balayla 2019), severe infectionNervous system: Cerebrovascular accidentMiscellaneous: Breakage of IUDContraindicationsHypersensitivity to levonorgestrel or any component of the formulation; pregnancy or suspected pregnancy; postcoital contraception; congenital or acquired uterine anomaly, including fibroids that distort the uterine cavity and would be incompatible with correct IUD placement; acute pelvic inflammatory disease or history of pelvic inflammatory disease (unless there has been a subsequent intrauterine pregnancy); postpartum endometritis or infected abortion within past 3 months; known or suspected uterine or cervical malignancy; untreated acute cervicitis or vaginitis (including bacterial vaginosis, known chlamydial or gonococcal cervical infection) or other lower genital tract infections until infection is controlled; conditions which increase susceptibility to pelvic infections; unremoved IUD; uterine bleeding of unknown etiology; acute hepatic disease or hepatic tumors (benign or malignant); current or history of known or suspected breast cancer or other hormone-sensitive cancer.Canadian labeling: Additional contraindications (not in US labeling): Bacterial endocarditis; recent trophoblastic disease while human chorionic gonadotropin (hCG) hormone levels are elevated; cervical dysplasia; known immunodeficiency or hematologic malignancy (Mirena)Warnings/PrecautionsConcerns related to adverse effects:• Bradycardia/syncope: Bradycardia or syncope may occur during insertion or removal of the IUD; use with caution in patients predisposed to these conditions.• Pelvic inflammatory disease: An increased incidence of group A streptococcal sepsis, pelvic inflammatory disease (PID) or endometritis (may be asymptomatic), and actinomycosis has been reported with use. Using aseptic technique during insertion is essential to minimizing the risk of serious infections. PID occurs more frequently within the first year and most often within the first month after insertion; risk is increased with multiple sexual partners. Patients with a history of PID or endometritis are at increased risk. If PID is diagnosed, treat according to current guidelines and reassess in 48 to 72 hours. If there is no clinical improvement, continue antibiotics and consider removal of device (CDC [Curtis 2016a]). Remove the device in patients with symptomatic actinomycosis and treat with appropriate antibiotics. Remove IUD in cases of recurrent endometritis or PID, or if an acute pelvic infection is severe or does not respond to treatment.• Seizure: Insertion or removal may be associated with seizure, especially in patients predisposed to seizures.Disease-related concerns:• Cervical or endometrial cancer: Do not use an IUD for pregnancy prevention in patients diagnosed with cervical or endometrial cancer prior to IUD insertion (may have an increased risk of bleeding or infection when the device is inserted). Patients diagnosed after insertion of an IUD may continue; however, the IUD will most likely need to be removed during treatment (CDC [Curtis 2016b]). If significant bleeding irregularities occur with prolonged use, conduct diagnostic tests to assess possible endometrial pathology (polyps or cancer).• Depression: Use with caution in patients with depression; may be more susceptible to recurrence of depressive episodes; consider removal of IUD for serious recurrence. Depression is not a contraindication to use of the IUD (CDC [Curtis 2016b]).• Gestational trophoblastic disease: Patients with gestational trophoblastic disease are at increased risk of adverse events if pregnancy occurs; use of the levonorgestrel IUD may be appropriate for prevention of pregnancy in some situations with close medical supervision. However, do not initiate therapy with a levonorgestrel IUD in patients with persistently elevated beta-hCG concentrations or malignant disease with evidence or suspicion of intrauterine disease due to risks of infection, hemorrhage, or perforation. Consider benefits of effective contraception versus risks of continuation/removal in patients who have a levonorgestrel IUD already in place (CDC [Curtis 2016b]).• Sepsis: Do not insert levonorgestrel IUD in patients with postpartum sepsis or immediately following a septic abortion (CDC [Curtis 2016b]).• Sexually transmitted infection: Do not initiate levonorgestrel IUD in patients with purulent cervicitis, chlamydial, or gonococcal infection. The IUD does not need to be removed if diagnosis occurs with the IUD in place, as long as there is treatment with appropriate antibiotics, symptoms resolve, and consideration is given to personal risk factors and patient preference (CDC [Curtis 2016a]; CDC [Curtis 2016b]).• Tuberculosis: Insert in patients with nonpelvic tuberculosis; do not initiate treatment in cases of pelvic infection and consider removal when pelvic infection occurs with the IUD in place (CDC [Curtis 2016b]).Special populations:• Body weight: Clinical trials did not exclude patients based on BMI (CDC [Curtis 2016a]).• Smoking: The risk of cardiovascular side effects increases in patients using estrogen-containing combined hormonal contraceptives and who smoke cigarettes, especially those who are >35 years of age. This risk relative to progestin-only contraceptives has not been established. Advise patients who take combination hormonal contraceptives not to smoke. Smoking is not a contraindication to use of the IUD (CDC [Curtis 2016b]).Dosage form specific issues:• Consent form: Some products provide a consent form; keep a copy of the form and lot number with the patient's medical record.• MRI: Only under specific conditions may an IUD be scanned safely by MRI (refer to manufacturer's labeling for requirements). Image quality may also be impaired if area of interest is relatively close to the device.Other warnings/precautions:• Appropriate use: IUD: Insert by a trained health care provider. Insertion and removal may be associated with pain and/or bleeding; consider analgesics prior to insertion. Removal of the device may be necessary for the following reasons: pelvic infection or disease, endometritis, symptomatic genital actinomycosis, uterine or cervical cancer, uterine or cervical perforation, partial expulsion, and pregnancy. Use with caution if any of the following conditions exist and consider removal if any of them arise during use: Coagulopathy or are receiving anticoagulants; marked increase of blood pressure; severe arterial disease, such as stroke or MI; exceptionally severe headache; and migraine, focal migraine with asymmetrical visual loss, or other symptoms indicating transient cerebral ischemia. In addition, consider removal if jaundice occurs during use.• HIV infection protection: Intrauterine devices do not protect against HIV infection or other sexually transmitted diseases (CDC [Curtis 2016b]).Metabolism/Transport EffectsSubstrate of CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potentialDrug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.Risk C: Monitor therapyCYP3A4 Inducers (Strong): May diminish the therapeutic effect of Levonorgestrel (IUD). CYP3A4 Inducers (Strong) may decrease the serum concentration of Levonorgestrel (IUD). Risk C: Monitor therapyMetyraPONE: Progestins may diminish the diagnostic effect of MetyraPONE.Management: Consider alternatives to the use of the metyrapone test in patients taking progestins. Risk D: Consider therapy modificationUlipristal: May diminish the therapeutic effect of Progestins. Progestins may diminish the therapeutic effect of Ulipristal. Risk X: Avoid combinationReproductive ConsiderationsEvaluate pregnancy status prior to insertion.Insert into the uterine cavity at any time during the menstrual cycle once it is determined that the patient is not pregnant. Insert immediately following a first trimester-induced or spontaneous abortion. Following pregnancy or a second trimester induced or spontaneous abortion, insert following removal of the placenta, or do not insert for at least 6 weeks or until involution of the uterus is complete. Insertion postpartum (immediate insertion within 10 minutes of placental delivery or interval insertion during the 6-week postpartum period) or following an abortion are safe despite a higher risk of expulsion immediately postpartum and following a second trimester abortion; offer regardless of breastfeeding status to help prevent rapid repeat and unintended pregnancies (ACOG 2017; CDC [Curtis 2016b]).All available forms of contraception, including the levonorgestrel IUD, can be considered for patients on gender-affirming testosterone therapy after evaluating the appropriateness of the method based on the patient's preferences and medical conditions (Bonnington 2020; Krempasky 2020).When treating patients with secondary amenorrhea (hypoestrogenism) due to primary ovarian failure, consider use of the levonorgestrel IUD in place of an oral progestogen for patients not wishing to become pregnant (ACOG 2017).Following removal of the device, ~71% to 85% of patients who wished to conceive became pregnant within 12 months.Pregnancy ConsiderationsUse during pregnancy or a suspected pregnancy is contraindicated.Patients who become pregnant with an IUD in place risk spontaneous or septic abortion; septicemia, septic shock, and death may occur. In addition, the likelihood of ectopic pregnancy is increased; miscarriage, sepsis, premature labor, and premature delivery may occur if pregnancy is continued. Removal of the device is recommended if strings are visible or removal can be done safely from the cervical canal. However, removal or manipulation of IUD or probing of the uterus may result in pregnancy loss. Consider use of an ultrasound to determine location of IUD prior to removal (CDC [Curtis 2016a]).Virilization of the female fetus has been observed following exposure to the levonorgestrel IUD.Breastfeeding ConsiderationsLevonorgestrel is present in breast milk.Two studies evaluated levonorgestrel breast milk concentrations following IUD insertion among patients 4 to 6 weeks postpartum (Heikkilä 1982; Shikary 1987). In 1 study, there was no correlation between dose and maternal serum or milk concentrations, although the authors calculated the infants received a relative dose of 1.2% of the maternal dose (Heikkilä 1982). In both studies, the milk/plasma ratio increased over time during the 4- and 12-week study periods (Heikkilä 1982; Shikary 1987). Levonorgestrel was also detected in the serum of breastfeeding infants (Shikary 1987).Concentrations of levonorgestrel and fat content in breast milk are similar 4 to 8 weeks after initial IUD insertion regardless if placement occurs immediately after delivery or at the first postpartum visit (4 to 8 weeks after delivery) (Hopelian 2021). The onset of lactogenesis and the duration of breastfeeding were not found to be influenced by the time of initial IUD placement (immediately after delivery or 4 to 8 weeks postpartum) (Turok 2017).In general, no adverse effects on the growth or development if the infant have been observed. Isolated cases of decreased milk production have been reported.Maternal plasma concentrations of levonorgestrel are dependent upon sex hormone binding globulin capacity, which is influenced by concomitant administration with estrogen or the postpartum status (Orme 1983). Risk of perforation with IUD is increased in patients who are lactating. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the patient.Following pregnancy, insert following removal of the placenta, or do not insert for at least 6 weeks postpartum or until involution of the uterus is complete. Insert immediately postpartum in patients who are breastfeeding, including patients who had a cesarean delivery. Risk of infection is not increased; risk of expulsion may be increased. Consider risk of expulsion along with the need for effective contraception and patient access to placement at a later time (CDC [Curtis 2016b]).Monitoring ParametersPrior to insertion: Assessment of pregnancy status; bimanual examination and cervical inspection; weight (optional; BMI at baseline may be helpful to monitor changes during therapy); STI screen (unless already screened according to CDC STD treatment guidelines) (CDC [Curtis 2016a]). Evaluate any unexplained vagin*l bleeding; exclude endometrial polyps or cancers (CDC [Curtis 2016b]). Complete medical and social history, which may determine conditions influencing an IUD use for contraception.Following insertion: Transvagin*l ultrasound may be used to check placement. Assess changes in health status (including medications) at routine follow-up visits (CDC [Curtis 2016a]). Re-examine following insertion (4 to 6 weeks Kyleena, Liletta, Mirena, Skyla; 4 to 12 weeks Jaydess [Canadian product]) and then yearly or more frequently if necessary. Threads should be visible; if length of thread has changed, device may have become displaced, broken, perforated the uterus, or expelled. If the IUD is not found in the uterus, consider further testing to confirm expulsion (eg, sonography, X-ray). Reassess pregnancy status if menstruation does not occur within 6 weeks of previous menstrual period. Monitor for significant changes in menstrual bleeding during prolonged use, Pap smear, BP, serum glucose in patients with diabetes. Evaluate patients presenting with lower abdominal pain for ectopic pregnancy (especially in association with missed periods) and ovarian cysts. Monitor for signs of infection. Monitor for signs/symptoms of thromboembolism in patients who require surgery with prolonged immobilization.Endometrial hyperplasia, treatment (off-label use): Endometrial sampling every 3 to 6 months, although most appropriate frequency has not been determined (ACOG 2015; Trimble 2012).Reference RangeKyleena: Plasma concentrations range from 175 ± 74 pg/mL (7 days following insertion) to 90 ± 35 pg/mL (after 5 years).Liletta: Plasma concentrations range from a peak of 252 ± 123 pg/mL (7 days following insertion) to 88 ± 37 pg/mL (after 8 years).Mirena: Plasma concentrations range from 150 to 200 pg/mL.Skyla, Jaydess [Canadian product]: Plasma concentrations range from a peak of 192 pg/mL (2 days following insertion) to 59 to 61 pg/mL (after 3 years).Mechanism of ActionPregnancy may be prevented through several mechanisms: Thickening of cervical mucus, which inhibits sperm passage through the uterus; inhibition of sperm survival; alteration of the endometrium. Inhibition of ovulation may also occur in some patients.Pharmaco*kineticsDuration: Prevention of pregnancy: Kyleena: Up to 5 years; Liletta, Mirena: Up to 8 years; Skyla, Jaydess [Canadian product]: Up to 3 years.Distribution: Vd: ~1.8 L/kg.Protein binding: Highly bound to albumin (~50%) and sex hormone-binding globulin (~47%) (Fotherby 1995).Metabolism: Hepatic via CYP3A4; forms inactive metabolites.Excretion: Urine (~45%); feces (~32%).Pricing: USIntrauterine Device (Kyleena Intrauterine)19.5 mg (per each): $1,259.09Intrauterine Device (Liletta (52 MG) Intrauterine)20.1 mcg/day (per each): $1,014.12Intrauterine Device (Mirena (52 MG) Intrauterine)20 mcg/day (per each): $1,259.09Intrauterine Device (Skyla Intrauterine)13.5 mg (per each): $1,048.40Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalContraplan II (EG);Fleree (LV);Janess (IL);Jaydess (AU, BE, BG, CH, CZ, DK, FR, GB, IE, KR, MT, NZ, RO, SG, SI);Levosert (BG, GB, HR, LU, MT);Lovosert (LV);Mirena (AE, AT, AU, BB, BE, BH, BR, CH, CL, CN, CO, CZ, DE, DK, EC, EE, EG, ES, FI, FR, GB, GR, HK, HR, HU, ID, IE, IL, IS, IT, JO, JP, KR, KW, LK, LT, LU, LV, MT, MX, MY, NL, NO, NZ, PE, PH, PL, PT, PY, QA, RO, RU, SE, SG, SI, TH, TR, UA, VN, ZA)For country code abbreviations (show table)<800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 40-NF 35). Rockville, MD: United States Pharmacopeia Convention; 2017:83-102.Abu Hashim H, Ghayaty E, El Rakhawy M. Levonorgestrel-releasing intrauterine system vs oral progestins for non-atypical endometrial hyperplasia: a systematic review and metaanalysis of randomized trials. Am J Obstet Gynecol. 2015;213(4):469-478. doi:10.1016/j.ajog.2015.03.037 [PubMed 25797236]American College of Obstetricians and Gynecologists (ACOG) Committee on Adolescent Health Care. Committee Opinion No. 668: Menstrual manipulation for adolescents with physical and developmental disabilities. Obstet Gynecol. 2016;128(2):e20-e25. doi:10.1097/AOG.0000000000001585 [PubMed 27454732]American College of Obstetricians and Gynecologists (ACOG) Committee on Adolescent Health Care. Committee Opinion No. 817: Options for prevention and management of menstrual bleeding in adolescent patients undergoing cancer treatment. Obstet Gynecol. 2021;137(1):e7-e15. doi:10.1097/AOG.0000000000004209 [PubMed 33399429]American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Gynecology, Long-Acting Reversible Contraception Work Group. Practice bulletin no. 186: long-acting reversible contraception: implants and intrauterine devices. Obstet Gynecol. 2017;130(5):e251-e269. [PubMed 29064972]American College of Obstetricians and Gynecologists (ACOG) Committee Opinion No. 760: Dysmenorrhea and endometriosis in the adolescent. Obstet Gynecol. 2018;132(6):e249-e258. doi:10.1097/AOG.0000000000002978 [PubMed 30461694]American College of Obstetricians and Gynecologists (ACOG) Committee Opinion No. 631. Endometrial intraepithelial neoplasia. Obstet Gynecol. 2015;125(5):1272-1278. doi:10.1097/01.AOG.0000465189.50026.20 [PubMed 25932867]American College of Obstetricians and Gynecologists (ACOG) Committee Opinion No. 698: Hormone therapy in primary ovarian insufficiency. Obstet Gynecol. 2017;129(5):e134-e141. doi:10.1097/AOG.0000000000002044 [PubMed 28426619]Anthony MS, Reed SD, Armstrong MA, et al. Design of the Association of Uterine Perforation and Expulsion of Intrauterine Device study: a multisite retrospective cohort study. Am J Obstet Gynecol. 2021;224(6):599.e1-599.e18. doi:10.1016/j.ajog.2021.01.003 [PubMed 33460585]Armstrong AJ, Hurd WW, Elguero S, et al. Diagnosis and management of endometrial hyperplasia. J Minim Invasive Gynecol. 2012;19(5):562-571. doi:10.1016/j.jmig.2012.05.009 [PubMed 22863972]Averbach SH, Ermias Y, Jeng G, et al. Expulsion of intrauterine devices after postpartum placement by timing of placement, delivery type, and intrauterine device type: a systematic review and meta-analysis. Am J Obstet Gynecol. 2020;223(2):177-188. doi:10.1016/j.ajog.2020.02.045 [PubMed 32142826]Balayla J, Gil Y, Mattina J, Al-Shehri E, Ziegler C. Streptococcal toxic shock syndrome after insertion of a levonorgestrel intrauterine device. J Obstet Gynaecol Can. 2019;41(12):1772-1774. doi:10.1016/j.jogc.2019.02.017 [PubMed 30981616]Barnhart KT. Clinical practice. Ectopic pregnancy. N Engl J Med. 2009;361(4):379-387. doi:10.1056/NEJMcp0810384 [PubMed 19625718]Bonnington A, Dianat S, Kerns J, et al. Society of Family Planning clinical recommendations: contraceptive counseling for transgender and gender diverse people who were female sex assigned at birth. Contraception. 2020;102(2):70-82. doi:10.1016/j.contraception.2020.04.001 [PubMed 32304766]Caliskan E, Oztürk N, Dilbaz BO, Dilbaz S. Analysis of risk factors associated with uterine perforation by intrauterine devices. Eur J Contracept Reprod Health Care. 2003;8(3):150-155. [PubMed 14667326]Carvalho N, Margatho D, Cursino K, Benetti-Pinto CL, Bahamondes L. Control of endometriosis-associated pain with etonogestrel-releasing contraceptive implant and 52-mg levonorgestrel-releasing intrauterine system: randomized clinical trial. Fertil Steril. 2018;110(6):1129-1136. doi:10.1016/j.fertnstert.2018.07.003 [PubMed 30396557]Carvalho NM, Chou V, Modesto W, Margatho D, Garcia EAL, Bahamondes L. Relationship between user satisfaction with the levonorgestrel-releasing intrauterine system and bleeding patterns. J Obstet Gynaecol Res. 2017;43(11):1732-1737. doi:10.1111/jog.13441 [PubMed 28833891]Curtis KM, Jatlaoui TC, Tepper NK, et al. US selected practice recommendations for contraceptive use, 2016. MMWR Recomm Rep. 2016a;65(4):1‐66. doi:10.15585/mmwr.rr6504a1 [PubMed 27467319]Curtis KM, Tepper NK, Jatlaoui TC, et al. US medical eligibility criteria for contraceptive use, 2016. MMWR Recomm Rep. 2016b;65(3):1‐103. doi:10.15585/mmwr.rr6503a1 [PubMed 27467196]Darney PD, Stuart GS, Thomas MA, Cwiak C, Olariu A, Creinin MD. Amenorrhea rates and predictors during 1 year of levonorgestrel 52 mg intrauterine system use. Contraception. 2018;97(3):210-214. doi:10.1016/j.contraception.2017.10.005 [PubMed 29038072]de Jonge ET, Yigit R, Molenberghs G, Straetmans D, Ombelet W. Predictors of oligoamenorrhea at 1-year follow-up in premenopausal women using a levonorgestrel-releasing intrauterine system. Contraception. 2007;76(2):91-95. doi:10.1016/j.contraception.2007.04.003 [PubMed 17656176]Dolapcioglu K, Boz A, Baloglu A. The efficacy of intrauterine versus oral progestin for the treatment of endometrial hyperplasia. A prospective randomized comparative study. Clin Exp Obstet Gynecol. 2013;40(1):122-126. [PubMed 23724525]Ferguson CA, Costescu D, Jamieson MA, Jong L. Transmural migration and perforation of a levonorgestrel intrauterine system: a case report and review of the literature. Contraception. 2016;93(1):81-86. doi:10.1016/j.contraception.2015.08.019 [PubMed 26386445]Fotherby K. Levonorgestrel. Clinical pharmaco*kinetics. Clin Pharmaco*kinet. 1995;28(3):203-215. [PubMed 7758251]Frank ML, DiMaria C. Levonorgestrel Subdermal Implants. Drug Saf. 1997;17(6):360-368. [PubMed 9429835]Gaetani SL, Garbade GJ, Haas SI, Roth KR, Kane KE. A ruptured ectopic pregnancy in a patient with an intrauterine device: a case report. Radiol Case Rep. 2021;16(12):3672-3674. doi:10.1016/j.radcr.2021.08.074 [PubMed 34630798]Graner S, Mc Taggart J, Nordström F, Melander E, Widenberg J, Kopp Kallner H. Levonorgestrel intrauterine contraceptive systems (13.5 mg and 52 mg) and risk of ectopic pregnancy. Acta Obstet Gynecol Scand. 2019;98(7):937-943. doi:10.1111/aogs.13564 [PubMed 30737766]Gupta J, Kai J, Middleton L, et al. Levonorgestrel Intrauterine System versus Medical Therapy for Menorrhagia. N Engl J Med. 2013;368(2):128-137. [PubMed 23301731]Hardeman J, Weiss BD. Intrauterine devices: an update. Am Fam Physician. 2014;89(6):445-450. [PubMed 24695563]Heikkilä M, Haukkamaa M, Luukkainen T. Levonorgestrel in milk and plasma of breast-feeding women with a levonorgestrel-releasing IUD. Contraception. 1982;25(1):41-49. [PubMed 6800691]Heinemann K, Reed S, Moehner S, Minh TD. Risk of uterine perforation with levonorgestrel-releasing and copper intrauterine devices in the European Active Surveillance Study on Intrauterine Devices. Contraception. 2015;91(4):274-279. doi:10.1016/j.contraception.2015.01.007 [PubMed 25601352]Hopelian NG, Simmons RG, Sanders JN, et al. Comparison of levonorgestrel level and creamatocrit in milk following immediate versus delayed postpartum placement of the levonorgestrel IUD. BMC Womens Health. 2021;21(1):33. doi:10.1186/s12905-021-01179-7 [PubMed 33478494]Imai A, Matsunami K, Takagi H, Ichigo S. Levonorgestrel-releasing intrauterine device used for dysmenorrhea: five-year literature review. Clin Exp Obstet Gynecol. 2014;41(5):495-498. [PubMed 25864246]Jaydess (levonorgestrel) [product monograph]. Mississauga, Ontario, Canada: Bayer Inc; November 2018.Kaunitz AM, Inki P. The levonorgestrel-releasing intrauterine system in heavy menstrual bleeding: a benefit-risk review. Drugs. 2012;72(2):193-215. doi:10.2165/11598960-000000000-00000 [PubMed 22268392]Kirkham YA, Ornstein MP, Aggarwal A, McQuillan S. No. 313-Menstrual suppression in special circ*mstances. J Obstet Gynaecol Can. 2019;41(2):e7-e17. doi:10.1016/j.jogc.2018.11.030 [PubMed 30638562]Krempasky C, Harris M, Abern L, Grimstad F. Contraception across the transmasculine spectrum. Am J Obstet Gynecol. 2020;222(2):134-143. doi:10.1016/j.ajog.2019.07.043 [PubMed 31394072]Kyleena (levonorgestrel-releasing intrauterine system) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; July 2021.Kyleena (levonorgestrel) [product monograph]. Mississauga, Ontario, Canada: Bayer Inc; September 2021.Li C, Zhao WH, Meng CX, et al. Contraceptive use and the risk of ectopic pregnancy: a multi-center case-control study. PLoS One. 2014;9(12):e115031. Published December 10, 2014. doi:10.1371/journal.pone.0115031 [PubMed 25493939]Liletta (levonorgestrel) [prescribing information]. Irvine, CA: Allergan USA Inc; November 2022.Madden T, McNicholas C, Zhao Q, Secura GM, Eisenberg DL, Peipert JF. Association of age and parity with intrauterine device expulsion. Obstet Gynecol. 2014;124(4):718-726. doi:10.1097/AOG.0000000000000475 [PubMed 25198262]Makena D, Gichere I, Warfa K. Levonorgestrel intrauterine system embedded within tubal ectopic pregnancy: a case report. J Med Case Rep. 2021;15(1):107. doi:10.1186/s13256-021-02723-7 [PubMed 33685513]Margatho D, Carvalho NM, Bahamondes L. Endometriosis-associated pain scores and biomarkers in users of the etonogestrel-releasing subdermal implant or the 52-mg levonorgestrel-releasing intrauterine system for up to 24 months. Eur J Contracept Reprod Health Care. 2020;25(2):133-140. doi:10.1080/13625187.2020.1725461 [PubMed 32069126]Maybin JA, Critchley HO. Medical management of heavy menstrual bleeding. Womens Health (Lond). 2016;12(1):27-34. doi:10.2217/whe.15.100 [PubMed 26695687]McNicholas C, Maddipati R, Zhao Q, et al. Use of the etonogestrel implant and levonorgestrel intrauterine device beyond the U.S. Food and Drug Administration-approved duration. Obstet Gynecol. 2015;125(3):599-604. doi:10.1097/AOG.0000000000000690. [PubMed 25730221]Mirena (levonorgestrel) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; August 2022.Mirena (levonorgestrel) [product monograph]. Mississauga, Ontario, Canada: Bayer Inc; September 2021.Mittermeier T, Farrant C, Wise MR. Levonorgestrel-releasing intrauterine system for endometrial hyperplasia. Cochrane Database Syst Rev. 2020;9(9):CD012658. doi:10.1002/14651858.CD012658.pub2 [PubMed 32909630]Nowitzki KM, Hoimes ML, Chen B, Zheng LZ, Kim YH. Ultrasonography of intrauterine devices. Ultrasonography. 2015;34(3):183-194. doi:10.14366/usg.15010 [PubMed 25985959]Orbo A, Vereide A, Arnes M, et al. Levonorgestrel-impregnated intrauterine device as treatment for endometrial hyperplasia: a national multicentre randomised trial. BJOG. 2014;121(4):477-486. doi:10.1111/1471-0528.12499 [PubMed 24286192]Orme ML, Back DJ, Breckenridge AM. Clinical pharmaco*kinetics of oral contraceptive steroids. Clin Pharmaco*kinet. 1983;8(2):95-136. [PubMed 6342899]Plan B (levonorgestrel). Saint-Laurent, Quebec, Canada: Paladin Labs Inc; July 2014.Pradhan S, Gomez-Lobo V. Hormonal contraceptives, intrauterine devices, gonadotropin-releasing hormone analogues and testosterone: menstrual suppression in special adolescent populations. J Pediatr Adolesc Gynecol. 2019;32(5S):S23-S29. doi:10.1016/j.jpag.2019.04.007 [PubMed 30980941]Preshaw PM. Oral contraceptives and the periodontium. Peridontol 2000. 2013;61(1):125-159. [PubMed 23240947]Rowlands S, Oloto E, Horwell DH. Intrauterine devices and risk of uterine perforation: current perspectives. Open Access J Contracept. 2016;7:19-32. doi:10.2147/OAJC.S85546 [PubMed 29386934]Schreiber CA, Teal SB, Blumenthal PD, Keder LM, Olariu AI, Creinin MD. Bleeding patterns for the Liletta® levonorgestrel 52 mg intrauterine system. Eur J Contracept Reprod Health Care. 2018;23(2):116-120. doi:10.1080/13625187.2018.1449825 [PubMed 29560743]Shikary ZK, Betrabet SS, Patel ZM, et al, "ICMR Task Force Study on Hormonal Contraception. Transfer of Levonorgestrel (LNG) Administered Through Different Drug Delivery Systems from the Maternal Circulation into the Newborn Infant's Circulation via Breast Milk," Contraception, 1987, 35(5):477-86. [PubMed 3113823]Sitruk-Ware R and Nath A, "Metabolic Effects of Contraceptive Steroids," Rev Endocr Metab Disord, 2011, 12(2):63-75. [PubMed 21538049]Skyla (levonorgestrel-releasing intrauterine system) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; July 2021.Somboonp*rn W, Panna S, Temtanakitpaisan T, Kaewrudee S, Soontrapa S. Effects of the levonorgestrel-releasing intrauterine system plus estrogen therapy in perimenopausal and postmenopausal women: systematic review and meta-analysis. Menopause. 2011;18(10):1060-1066. doi:10.1097/gme.0b013e31821606c5 [PubMed 21720280]Trimble CL, Method M, Leitao M, et al. Management of endometrial precancers. Obstet Gynecol. 2012;120(5):1160-1175. doi:10.1097/AOG.0b013e31826bb121 [PubMed 23090535]Turok DK, Gero A, Simmons RG, et al. Levonorgestrel vs. copper intrauterine devices for emergency contraception. N Engl J Med. 2021;384(4):335-344. doi:10.1056/NEJMoa2022141 [PubMed 33503342]Turok DK, Leeman L, Sanders JN, et al. Immediate postpartum levonorgestrel intrauterine device insertion and breast-feeding outcomes: a noninferiority randomized controlled trial. Am J Obstet Gynecol. 2017;217(6):665.e1-665.e8. doi:10.1016/j.ajog.2017.08.003 [PubMed 28842126]US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. http://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf. Updated September 2016. Accessed October 5, 2016.Varila E, Wahlström T, Rauramo I. A 5-year follow-up study on the use of a levonorgestrel intrauterine system in women receiving hormone replacement therapy. Fertil Steril. 2001;76(5):969-973. doi:10.1016/s0015-0282(01)02846-1 [PubMed 11704119]Wildemeersch D, Janssens D, Schacht E, Pylyser K, de Wever N. Intrauterine levonorgestrel delivered by a frameless system, combined with systemic estrogen: acceptability and endometrial safety after 3 years of use in peri- and postmenopausal women. Gynecol Endocrinol. 2005;20(6):336-342. doi:10.1080/09513590500099156 [PubMed 16019384]Wildemeersch D, Pylyser K, De Wever N, Pauwels P, Tjalma W. Endometrial safety after 5 years of continuous combined transdermal estrogen and intrauterine levonorgestrel delivery for postmenopausal hormone substitution. Maturitas. 2007;57(2):205-209. doi:10.1016/j.maturitas.2006.11.010 [PubMed 17227699]Yucel N, Baskent E, Karamustafaoglu Balci B, Goynumer G. The levonorgestrel-releasing intrauterine system is associated with a reduction in dysmenorrhoea and dyspareunia, a decrease in CA 125 levels, and an increase in quality of life in women with suspected endometriosis. Aust N Z J Obstet Gynaecol. 2018;58(5):560-563. doi:10.1111/ajo.12773 [PubMed 29359457]Topic 104541 Version 181.0

CloseLevonorgestrel intrauterine device: Pediatric drug informationLevonorgestrel intrauterine device: Pediatric drug information(For additional information see "Levonorgestrel intrauterine device: Drug information" and see "Levonorgestrel intrauterine device: Patient drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USKyleena;Liletta (52 MG);Mirena (52 MG);SkylaBrand Names: CanadaKyleena;MirenaTherapeutic CategoryContraceptive;ProgestinDosing: PediatricContraception or heavy menstrual bleedingContraception (Kyleena, Liletta, Mirena, Skyla, Jaydess) or heavy menstrual bleeding (Mirena):Postmenarche patients: Intrauterine device (IUD):Initiation of therapy: In patients not currently using a hormonal contraceptive or intrauterine contraception, the IUD may be inserted into the uterine cavity at any time during the menstrual cycle once it is determined that the patient is not pregnant. Backup contraception is not needed if insertion is within 7 days of onset of menstruation. If insertion occurs >7 days after menstrual bleeding started, a barrier method of contraception must be used for 7 days unless the patient abstains from sexual intercourse.Continuation of therapy: Duration of action is product-specific. When it is time to replace, the dated IUD is removed and replaced as follows with a new device immediately, and at any time during menstrual cycle as long as the patient is not pregnant:Kyleena: Replace by the end of 5 years. Initially releases levonorgestrel ~17.5 mcg/day after 24 days, then rate subsequently decreases; the average release rate over 5 years is levonorgestrel ~9 mcg/day. Do not leave device in place for >5 years.Liletta: Replace by the end of 6 years. Initially releases levonorgestrel 20 mcg/day, then rate subsequently decreases; the average release rate over 6 years is levonorgestrel ~14.3 mcg/day. Do not leave in place for >6 years.Mirena: Replace by the end of 8 years. Initially releases levonorgestrel 21 mcg/day, then rate subsequently decreases to ~11 mcg/day after 5 years and 7 mcg/day after 8 years. Do not leave device in place for >8 years.Skyla, Jaydess [Canadian product]: Replace by the end of 3 years. Initially releases levonorgestrel ~14 mcg/day after 24 days, then rate subsequently decreases; mean release rate over 3 years is levonorgestrel ~6 mcg/day. Do not leave device in place for >3 years.Patients Switching from a Different Contraceptive to Levonorgestrel IUDCurrent MethodInstructions for Switching to Levonorgestrel IUDa When switching from a copper IUD, if sexual intercourse occurred after the start of the current cycle, and it has been >5 days since bleeding began, consider administering an emergency contraceptive (CDC [Curtis 2016a]).Hormonal contraceptive (oral, transdermal, vagin*l)Levonorgestrel IUD may be inserted anytime, including hormone-free interval of the previous method. If inserted during active use of the previous method, continue previous method for 7 days after insertion or until the end of the current treatment cycle.If using continuous hormonal contraception, continue previous method for 7 days after insertion.Injectable progestinLevonorgestrel IUD may be inserted at any time. If inserted >13 weeks after the last injection, a barrier method of contraception should also be used for 7 days.Implant or another intrauterine system (IUS)aLevonorgestrel IUD may be inserted on the same day the implant or IUS is removed, any time during the menstrual cycle.Switching from levonorgestrel IUD to a different contraceptive: If the patient wishes to change to a different method of birth control, may remove the device during the first 7 days of menstrual cycle and begin the new therapy. If the device is not removed during the first 7 days of menstruation (or if the patient has irregular menstrual cycles or amenorrhea) and wants to start a different method of birth control, start the new method at least 7 days prior to device removal, otherwise, a backup barrier contraceptive should be used for 7 days after the device is removed unless the patient abstains from vagin*l intercourse.Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricThere are no dosage adjustments provided in the manufacturer's labeling (has not been studied).Dosing: Hepatic Impairment: PediatricPostmenarche patients: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use of the intrauterine device is contraindicated with active hepatic disease or hepatic tumor.Dosing: Adult(For additional information see "Levonorgestrel intrauterine device: Drug information")Abnormal uterine bleeding, nonacuteAbnormal uterine bleeding, nonacute (52 mg devices: Mirena, Liletta [off-label use]): Note: Not indicated for management of acute abnormal bleeding (ie, excessively heavy or prolonged bleeding that requires urgent evaluation).Initiation of therapy: For patients not currently using a hormonal contraceptive or intrauterine contraception, insert the IUD into the uterine cavity at any time during the menstrual cycle once it is determined that the patient is not pregnant. Back-up contraception is not needed if insertion is within 7 days of onset of menstruation. If insertion occurs >7 days after onset of menses, use a barrier method of contraception for 7 days.Continuation of therapy: Menstrual suppression may attenuate prior to recommended durations for contraception, requiring more frequent replacement of the device (Kaunitz 2012). When it is time to replace IUD, remove and replace with a new device immediately, or at any time during menstrual cycle as follows, provided the patient is not pregnant:Mirena: In general, replace by the end of 5 years for nonacute abnormal uterine bleeding. Initially releases levonorgestrel 21 mcg/day, then rate subsequently decreases to ~11 mcg/day after 5 years and to 7 mcg/day after 8 years. If bleeding is controlled and contraception is still desired, may leave in place for up to 8 years.Liletta (off-label use): Duration of therapy not clearly established for nonacute abnormal uterine bleeding (Kaunitz 2012). Initially releases levonorgestrel 20 mcg/day, then rate subsequently decreases to ~6.5 mcg/day after 8 years. If bleeding is controlled and contraception is still desired, may leave in place up to 8 years.Note: For instruction on switching from a different contraceptive and use after childbirth, abortion, or miscarriage, refer to dosing for "Contraception."ContraceptionContraception:Initiation of therapy: In patients not currently using a hormonal contraceptive or intrauterine contraception, insert IUD into the uterine cavity at any time during the menstrual cycle once it is determined that the patient is not pregnant. Back-up contraception is not needed if insertion is within 7 days of onset of menstruation. If insertion occurs >7 days after menstrual bleeding started, use a barrier method of contraception for 7 days unless the patient abstains from sexual intercourse.Continuation of therapy: When it is time to replace IUD, remove and replace immediately or at any time during menstrual cycle as follows, as long as the patient is not pregnant:Kyleena: Replace by the end of 5 years. Initially releases levonorgestrel ~17.5 mcg/day after 24 days, then rate subsequently decreases; the average release rate over 5 years is levonorgestrel ~9 mcg/day. Do not leave device in place for >5 years.Liletta: Replace by the end of 8 years. Initially releases levonorgestrel ~20 mcg/day, then rate subsequently decreases; the average release rate over 8 years is levonorgestrel ~13.5 mcg/day. Do not leave in place for >8 years.Mirena: Replace by the end of 8 years. Initially releases levonorgestrel 21 mcg/day, then rate subsequently decreases to ~11 mcg/day after 5 years and 7 mcg/day after 8 years. Do not leave device in place for >8 years.Skyla, Jaydess [Canadian product]: Replace by the end of 3 years. Initially releases levonorgestrel ~14 mcg/day after 24 days, then rate subsequently decreases; mean release rate over 3 years is levonorgestrel ~6 mcg/day. Do not leave device in place for >3 years.Patients Switching from a Different Contraceptive to Levonorgestrel IUDCurrent methodInstructions for switching to levonorgestrel IUDa When switching from a copper IUD, if sexual intercourse occurred after the start of the current cycle, and it has been >5 days since bleeding began, consider administering an emergency contraceptive (CDC [Curtis 2016a]).Hormonal contraceptive (oral, transdermal, vagin*l)Insert levonorgestrel IUD at any time, including hormone-free interval of the previous method. If inserted during active use of the previous method, continue previous method for 7 days after insertion or until the end of the current treatment cycle.If using continuous hormonal contraception, continue previous method for 7 days after insertion.Injectable progestinInsert levonorgestrel IUD at any time. If inserted >13 weeks after the last injection, use a barrier method of contraception for 7 days.Implant or another intrauterine system (IUS)aInsert levonorgestrel IUD on the same day the implant or IUS is removed, any time during the menstrual cycle.Switching from levonorgestrel IUD to a different contraceptive: If the patient wishes to change to a different method of birth control, remove IUD during the first 7 days of menstrual cycle and begin the new therapy. If the IUD is not removed during the first 7 days of menstruation (or if the patient has irregular menstrual cycles or amenorrhea), start the new method at least 7 days prior to IUD removal, otherwise, use a back-up barrier contraceptive for 7 days after the IUD is removed, unless the patient abstains from vagin*l intercourse.Use of Levonorgestrel IUD After Childbirth, Abortion, or Miscarriagea Product labeling recommends insertion following removal of the placenta, or waiting at least 6 weeks following delivery, or until the uterus is fully involuted. According to evidence-based guidelines, insertion postpartum (immediate insertion within 10 minutes of placental delivery or interval insertion during the 6-week postpartum period) or following an abortion are safe despite a higher risk of expulsion immediately postpartum or following a second trimester abortion and may be offered regardless of breastfeeding status to help prevent rapid repeat and unintended pregnancies (ACOG 2017; CDC [Curtis 2016b]).b Back up contraception is needed for 7 days unless IUD is placed at the time of surgical abortion. Do not administer immediately following a septic abortion (CDC [Curtis 2016a]).Use after childbirth (immediate)Insert levonorgestrel IUD after removal of the placenta; backup contraception is not needed.aUse after childbirth (interval insertion following complete involution of the uterus)Do not insert levonorgestrel IUD <6 weeks after childbirth or if the uterus is not fully involuted.aInsert at any time if it is determined that the patient is not pregnant. If menstruation has not yet resumed, consider the possibility of ovulation and conception occurring prior to IUD insertion.Back-up contraception is not needed if insertion is within 7 days of onset of menstruation. If insertion occurs >7 days after menstrual bleeding started, use a barrier method of contraception for 7 days unless the patient abstains from sexual intercourse.The risk of perforation is increased in lactating patients.Use after first trimester abortion or miscarriagebInsert levonorgestrel IUD immediately after a first-trimester abortion or miscarriage.Use after second trimester abortion or miscarriagebRefer to instructions for use after childbirth.DysmenorrheaDysmenorrhea (off-label use): 52 mg device: Refer to dosing for "Contraception" (ACOG 2018).Endometrial hyperplasia, treatmentEndometrial hyperplasia, treatment (off-label use): 52 mg device: Insert into the intrauterine cavity for hyperplasia without atypia or atypical endometrial hyperplasia/endometrial intraepithelial neoplasia. IUDs that contain levonorgestrel 52 mg in a reservoir initially release ~20 mcg/day then progressively decrease to ~10 mcg/day after 5 years. Replace after 5 years; however, the optimal duration of treatment is not known (ACOG 2015; Armstrong 2012; Orbo 2014; Trimble 2012).Estrogen therapy-associated endometrial hyperplasia, preventionEstrogen therapy-associated endometrial hyperplasia, prevention (off-label use) (alternative agent):Note: Based on data in patients who are peri- and postmenopausal; may be considered as an alternative for prevention of endometrial hyperplasia in patients with a uterus receiving estrogen therapy (eg, for vasomotor symptoms associated with menopause or secondary amenorrhea) but who are unable to tolerate oral progestogen (ie, a natural progesterone or synthetic progestin) regimens, particularly if patients desire or need contraception and/or treatment for heavy menstrual bleeding (Somboonp*rn 2011; Varila 2001; Wildemeersch 2005; Wildemeersch 2007).All devices: Confirm no possibility of pregnancy. Insert into the intrauterine cavity. In patients with menstrual cycles, may insert at any time. Discontinue when estrogen therapy is discontinued, unless also being used for contraception. Refer also to dosing for “Contraception.” Note: Limited data are available with an IUD that released LNG-20 mcg/day for up to 5 years; however, LNG-14 mcg/day for up to 3 years has also been studied (Somboonp*rn 2011; Varila 2001; Wildemeersch 2005; Wildemeersch 2007).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultThere are no dosage adjustments provided in the manufacturer's labeling (has not been studied).Dosing: Hepatic Impairment: AdultThere are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use of the intrauterine device is contraindicated with active hepatic disease or hepatic tumor.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Intrauterine Device, Intrauterine: Kyleena: 19.5 mgLiletta (52 MG): 20.1 mcg/dayMirena (52 MG): 20 mcg/daySkyla: 13.5 mgGeneric Equivalent Available: USNoDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Intrauterine Device, Intrauterine: Kyleena: 19.5 mgMirena: 52 mgAdministration: PediatricIntrauterine device (IUD): To be inserted into the uterine cavity by a health care professional. Consider administering analgesics or cervical anesthetic prior to insertion. Insert into the uterine cavity to the recommended depth with the provided insertion device; should not be forced into the uterus. If necessary, dilate the cervical canal and consider using a paracervical block. Transvagin*l ultrasound may be used to check proper placement. Remove if not positioned properly and insert a new IUD; do not reinsert removed IUD. Exclude uterine perforation if exceptional pain or bleeding occurs after insertion. Ensure device is intact after removal. Check expiration of IUD prior to insertion. Refer to manufacturer's labeling for additional administration instructions. For patients on gender-affirming testosterone therapy, consider pretreating with vagin*l estrogen for 2 weeks prior to insertion because testosterone may cause vagin*l atrophy (Bonnington 2020). In case of breakage or embedment of IUD in the myometrium, analgesia, paracervical anesthesia, cervical dilation, alligator forceps, or hysteroscopy may be used to aid in removal.Administration: AdultTo be inserted into the uterine cavity. Consider administering analgesics or cervical anesthetic prior to insertion. Insert into the uterine cavity to the recommended depth with the provided insertion device; do not force into the uterus. If necessary, dilate the cervical canal and consider using a paracervical block. Transvagin*l ultrasound may be used to check proper placement. Remove if not positioned properly and insert a new IUD; do not reinsert removed IUD. Exclude uterine perforation if exceptional pain or bleeding occurs after insertion. Ensure device is intact after removal. Check expiration of IUD prior to insertion. Use of the provided inserter and directions for insertion are different for immediate insertion after childbirth or second-trimester abortion, or miscarriage. Refer to manufacturer's labeling for additional administration instructions.Because testosterone may cause vagin*l atrophy, consider pretreating with vagin*l estrogen for 2 weeks prior to insertion to patients on gender-affirming testosterone therapy (Bonnington 2020).Dysmenorrhea (off-label use): 52 mg device: Consider placing IUD during diagnostic laparoscopy to minimize pain of insertion for patients undergoing this procedure (ACOG 2018).In case of breakage or embedment of IUD in the myometrium, analgesia, paracervical anesthesia, cervical dilation, alligator forceps, or hysteroscopy may be used to aid in removal.Hazardous Drugs Handling ConsiderationsHazardous agent (NIOSH 2016 [group 2]).Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. Double gloving and a protective gown are recommended for administration (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).Storage/StabilityJaydess [Canadian product]: Store at 15°C to 30°C (59°F to 86°F).Liletta: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Protect from light.Kyleena, Mirena, Skyla: Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).UsePrevention of pregnancy (FDA approved in postmenarche pediatric and adult patients); treatment of heavy menstrual bleeding in patients who also choose to use an intrauterine device (IUD) for contraception (Mirena: FDA approved in postmenarche pediatric and adult patients).Medication Safety IssuesHigh alert medication:The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.Adverse Reactions (Significant): ConsiderationsBleeding irregularitiesLevonorgestrel intrauterine device (IUD) is associated with changes in gynecological bleeding patterns, including increased number of bleeding/spotting days, irregular bleeding patterns, oligomenorrhea, and amenorrhea. Rates of frequent or prolonged bleeding rapidly decline with continued use (Ref). Menstrual blood loss can decrease by 96% after 1 year of use (Ref). Approximately 20% of women will continue to experience bleeding irregularities with continued use (Ref). Bleeding irregularities have been associated with dissatisfaction and discontinuation in some users (Ref).Mechanism: Dose-related; in addition to impacting ovulation, bleeding irregularities may be due to changes in the endometrium due to sustained progestogen exposure, decrease in steroid hormone receptors, and lack of local estrogen exposure (Ref).Onset: Varied; the first 3 to 6 months of use are generally most associated with bleeding irregularities (Ref). Twenty-six percent of users reported frequent bleeding in the first 90 days of use versus <10% in the subsequent 90 days (Ref).Risk factors:• Products containing higher doses of levonorgestrel are associated with more amenorrhea (Ref)• Self-reported duration of menstrual flow of <7 days is predictive of amenorrhea at 12 months (Ref)• Duration of menses <5 days and absence of heavy menstrual bleeding at baseline is predicative of oligomenorrhea at 12 months (Ref)Device expulsionDevice expulsion is the passage of the intrauterine device (IUD) either partially or completely through the external cervical os (Ref). Expulsion may be asymptomatic and discovered by a patient when the threads are shorter than normal, uneven, or can no longer be felt (Ref). Expulsion may also be associated with pain, bleeding, or a change in bleeding patterns (such as increased bleeding) (Ref).Onset: Varied; highest rate of expulsion is during the first year after placement of device (Ref).Risk factors: • Immediate/early (<4 weeks) postpartum placement (Ref)• Immediate postabortion placement (Ref)• Insertion into uterus <5.5 cm• Insertion into uterus not completely involuted at the time of insertion• Parous females (Ref)• vagin*l delivery (Ref)• Not breastfeeding at time of insertionEctopic pregnancyRates of ectopic pregnancy (EP) with levonorgestrel intrauterine device (IUD) use are rare and lower than the general population with estimated incidence of 0.02 to 0.2 per 100 patient-years (Ref). However, 25% to 50% of pregnancies that occur while a device is in place are likely to be ectopic with an associated risk of rupture and high morbidity (fertility loss, pregnancy loss, septic abortion) and mortality (Ref).Mechanism: Unknown; increased EP risk may be due to failure of the device (Ref). Progesterone may facilitate ciliary dysfunction and impair smooth muscle contraction within the fallopian tube, resulting in tubal retention and subsequent implantation (Ref). If the device migrates, an inflammatory reaction may occur, interfering with tubal function (Ref).Onset: Varied; risk may be higher during the first year of use (Ref); however, presentation has occurred after various durations of therapy (Ref). Case reports describe diagnosis after several days of vagin*l bleeding, vomiting, lower abdominal pain, loose stools, and abdominal fullness worsening over several days (Ref).Risk factors:• Lower IUD dose (Ref)• First year of use (Ref)• Device migration; however, in one case report, EP occurred with a correctly positioned device (Ref)• Leaving device in place longer than indicated (Ref)• History of EP• Tubal surgery• Pelvic infectionPerforation/embedded devicePenetration or embedment into the uterine wall or cervix is uncommon but is an important risk to consider with intrauterine device (IUD) use (Ref). Data from the FDA mandated study APEX-IUD (Association of Uterine Perforation and Expulsion of Intrauterine Device Study) approximates the risk at 1 to 2 perforations per 1,000 insertions (Ref). Uterine perforation may be asymptomatic and not discovered for months or years after insertion (Ref). Perforation may reduce contraceptive efficacy and result in pregnancy. Delayed detection or removal in cases of perforation may result in migration of IUD outside of uterine cavity, adhesions, peritonitis, intestinal perforations, intestinal obstruction, abscesses, and erosion of adjacent viscera.Mechanism: Complete perforation generally occurs during insertion when the IUD is forced into or through the uterine wall infiltrating all uterine layers (endometrium, myometrium, and serosa) (Ref). Partial perforation or embedment is less common but takes place when the IUD penetrates the uterine wall and remains in the myometrium (Ref). While most perforations occur during insertion, secondary perforations/embedment may occur via gradual erosion through the myometrium (Ref). Hence, a partial perforation may eventually become a complete perforation (Ref). Uterine contractions may be a factor contributing to perforations and transmural migration (Ref).Onset: Varied; most cases are not recognized at the time of insertion. Discovery of penetration/embedment may be months to years after insertion of IUD (Ref).Risk factors: • Postpartum placement up to 36 weeks (Ref)• Insertion into uterus <5.5 cm• Insertion into uterus when fixed, retroverted, or not completely involuted (Ref)• Breastfeeding at time of insertion (Ref)• Amenorrheic at time of insertion (Ref)• Insertion by a less experienced clinician (Ref)• Lower parity (Ref)• Higher number of previous abortions (Ref)• Altered myometrial integrity (eg, postmenopausal, prolonged concurrent steroid use) (Ref)Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adolescents and adults.>10%:Dermatologic: Acne vulgaris (7% to 15%)Endocrine & metabolic: Amenorrhea (≤40%; increases with duration of treatment)Gastrointestinal: Abdominal pain (≤23%)Genitourinary: Bacterial vaginosis (19%), gynecological bleeding (including decreased, increased, heavy, irregular, prolonged, unscheduled, frequent and infrequent uterine bleeding), ovarian cyst (5% to 22%), pelvic pain (≤23%), vagin*l discharge (4% to 15%), vagin*l mycosis (19%), vulvovaginitis (11% to 24%)Nervous system: Headache (≤16%), migraine (≤16%)1% to 10%:Dermatologic: Alopecia (1%), seborrhea (1% to 2%)Endocrine & metabolic: Hirsutism (<5%), weight gain (6%)Gastrointestinal: Abdominal distress, nausea, vomitingGenitourinary: Bacterial reproductive infection (1% to 4%), breast tenderness (including discomfort: ≤10%), dysmenorrhea (6% to 9%), dyspareunia (9%), endometritis (≤2%), female birth control expulsion from genital tract (3% to 5%; partial and complete), mastalgia (≤10%), pelvic inflammatory disease (<5%), uterine spasm (2%)Nervous system: Anxiety (9%), depressed mood (≤6%), depression (≤8%), mood changes (6%)Neuromuscular & skeletal: Back pain (6% to 8%)<1%: Genitourinary: Ectopic pregnancy, uterine perforationPostmarketing:Cardiovascular: Arterial thromboembolism, deep vein thrombosis, increased blood pressure, pulmonary embolismHematologic & oncologic: Malignant neoplasm of breastHypersensitivity: AngioedemaInfection: Sepsis (including Group A streptococcal sepsis) (Balayla 2019), severe infectionNervous system: Cerebrovascular accidentMiscellaneous: Breakage of IUDContraindicationsHypersensitivity to levonorgestrel or any component of the formulation; pregnancy or suspected pregnancy; postcoital contraception; congenital or acquired uterine anomaly, including fibroids that distort the uterine cavity and would be incompatible with correct IUD placement; acute pelvic inflammatory disease or history of pelvic inflammatory disease (unless there has been a subsequent intrauterine pregnancy); postpartum endometritis or infected abortion within past 3 months; known or suspected uterine or cervical malignancy; untreated acute cervicitis or vaginitis (including bacterial vaginosis, known chlamydial or gonococcal cervical infection) or other lower genital tract infections until infection is controlled; conditions which increase susceptibility to pelvic infections; unremoved IUD; uterine bleeding of unknown etiology; acute hepatic disease or hepatic tumors (benign or malignant); current or history of known or suspected breast cancer or other hormone-sensitive cancer.Canadian labeling: Additional contraindications (not in US labeling): Bacterial endocarditis; recent trophoblastic disease while human chorionic gonadotropin (hCG) hormone levels are elevated; cervical dysplasia; known immunodeficiency or hematologic malignancy (Mirena)Warnings/PrecautionsConcerns related to adverse effects:• Bradycardia/syncope: Bradycardia or syncope may occur during insertion or removal of the IUD; use with caution in patients predisposed to these conditions.• Pelvic inflammatory disease: An increased incidence of group A streptococcal sepsis, pelvic inflammatory disease (PID) or endometritis (may be asymptomatic), and actinomycosis has been reported with use. Using aseptic technique during insertion is essential to minimizing the risk of serious infections. PID occurs more frequently within the first year and most often within the first month after insertion; risk is increased with multiple sexual partners. Patients with a history of PID or endometritis are at increased risk. If PID is diagnosed, treat according to current guidelines and reassess in 48 to 72 hours. If there is no clinical improvement, continue antibiotics and consider removal of device (CDC [Curtis 2016a]). Remove the device in patients with symptomatic actinomycosis and treat with appropriate antibiotics. Remove IUD in cases of recurrent endometritis or PID, or if an acute pelvic infection is severe or does not respond to treatment.• Seizure: Insertion or removal may be associated with seizure, especially in patients predisposed to seizures.Disease-related concerns:• Cervical or endometrial cancer: Do not use an IUD for pregnancy prevention in patients diagnosed with cervical or endometrial cancer prior to IUD insertion (may have an increased risk of bleeding or infection when the device is inserted). Patients diagnosed after insertion of an IUD may continue; however, the IUD will most likely need to be removed during treatment (CDC [Curtis 2016b]). If significant bleeding irregularities occur with prolonged use, conduct diagnostic tests to assess possible endometrial pathology (polyps or cancer).• Depression: Use with caution in patients with depression; may be more susceptible to recurrence of depressive episodes; consider removal of IUD for serious recurrence. Depression is not a contraindication to use of the IUD (CDC [Curtis 2016b]).• Gestational trophoblastic disease: Patients with gestational trophoblastic disease are at increased risk of adverse events if pregnancy occurs; use of the levonorgestrel IUD may be appropriate for prevention of pregnancy in some situations with close medical supervision. However, do not initiate therapy with a levonorgestrel IUD in patients with persistently elevated beta-hCG concentrations or malignant disease with evidence or suspicion of intrauterine disease due to risks of infection, hemorrhage, or perforation. Consider benefits of effective contraception versus risks of continuation/removal in patients who have a levonorgestrel IUD already in place (CDC [Curtis 2016b]).• Sepsis: Do not insert levonorgestrel IUD in patients with postpartum sepsis or immediately following a septic abortion (CDC [Curtis 2016b]).• Sexually transmitted infection: Do not initiate levonorgestrel IUD in patients with purulent cervicitis, chlamydial, or gonococcal infection. The IUD does not need to be removed if diagnosis occurs with the IUD in place, as long as there is treatment with appropriate antibiotics, symptoms resolve, and consideration is given to personal risk factors and patient preference (CDC [Curtis 2016a]; CDC [Curtis 2016b]).• Tuberculosis: Insert in patients with nonpelvic tuberculosis; do not initiate treatment in cases of pelvic infection and consider removal when pelvic infection occurs with the IUD in place (CDC [Curtis 2016b]).Special populations:• Body weight: Clinical trials did not exclude patients based on BMI (CDC [Curtis 2016a]).• Smoking: The risk of cardiovascular side effects increases in patients using estrogen-containing combined hormonal contraceptives and who smoke cigarettes, especially those who are >35 years of age. This risk relative to progestin-only contraceptives has not been established. Advise patients who take combination hormonal contraceptives not to smoke. Smoking is not a contraindication to use of the IUD (CDC [Curtis 2016b]).Dosage form specific issues:• Consent form: Some products provide a consent form; keep a copy of the form and lot number with the patient's medical record.• MRI: Only under specific conditions may an IUD be scanned safely by MRI (refer to manufacturer's labeling for requirements). Image quality may also be impaired if area of interest is relatively close to the device.Other warnings/precautions:• Appropriate use: IUD: Insert by a trained health care provider. Insertion and removal may be associated with pain and/or bleeding; consider analgesics prior to insertion. Removal of the device may be necessary for the following reasons: pelvic infection or disease, endometritis, symptomatic genital actinomycosis, uterine or cervical cancer, uterine or cervical perforation, partial expulsion, and pregnancy. Use with caution if any of the following conditions exist and consider removal if any of them arise during use: Coagulopathy or are receiving anticoagulants; marked increase of blood pressure; severe arterial disease, such as stroke or MI; exceptionally severe headache; and migraine, focal migraine with asymmetrical visual loss, or other symptoms indicating transient cerebral ischemia. In addition, consider removal if jaundice occurs during use.• HIV infection protection: Intrauterine devices do not protect against HIV infection or other sexually transmitted diseases (CDC [Curtis 2016b]).Metabolism/Transport EffectsSubstrate of CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potentialDrug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions programAntidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.Risk C: Monitor therapyCYP3A4 Inducers (Strong): May diminish the therapeutic effect of Levonorgestrel (IUD). CYP3A4 Inducers (Strong) may decrease the serum concentration of Levonorgestrel (IUD). Risk C: Monitor therapyMetyraPONE: Progestins may diminish the diagnostic effect of MetyraPONE.Management: Consider alternatives to the use of the metyrapone test in patients taking progestins. Risk D: Consider therapy modificationUlipristal: May diminish the therapeutic effect of Progestins. Progestins may diminish the therapeutic effect of Ulipristal. Risk X: Avoid combinationReproductive ConsiderationsEvaluate pregnancy status prior to insertion.Insert into the uterine cavity at any time during the menstrual cycle once it is determined that the patient is not pregnant. Insert immediately following a first trimester-induced or spontaneous abortion. Following pregnancy or a second trimester induced or spontaneous abortion, insert following removal of the placenta, or do not insert for at least 6 weeks or until involution of the uterus is complete. Insertion postpartum (immediate insertion within 10 minutes of placental delivery or interval insertion during the 6-week postpartum period) or following an abortion are safe despite a higher risk of expulsion immediately postpartum and following a second trimester abortion; offer regardless of breastfeeding status to help prevent rapid repeat and unintended pregnancies (ACOG 2017; CDC [Curtis 2016b]).All available forms of contraception, including the levonorgestrel IUD, can be considered for patients on gender-affirming testosterone therapy after evaluating the appropriateness of the method based on the patient's preferences and medical conditions (Bonnington 2020; Krempasky 2020).When treating patients with secondary amenorrhea (hypoestrogenism) due to primary ovarian failure, consider use of the levonorgestrel IUD in place of an oral progestogen for patients not wishing to become pregnant (ACOG 2017).Following removal of the device, ~71% to 85% of patients who wished to conceive became pregnant within 12 months.Pregnancy ConsiderationsUse during pregnancy or a suspected pregnancy is contraindicated.Patients who become pregnant with an IUD in place risk spontaneous or septic abortion; septicemia, septic shock, and death may occur. In addition, the likelihood of ectopic pregnancy is increased; miscarriage, sepsis, premature labor, and premature delivery may occur if pregnancy is continued. Removal of the device is recommended if strings are visible or removal can be done safely from the cervical canal. However, removal or manipulation of IUD or probing of the uterus may result in pregnancy loss. Consider use of an ultrasound to determine location of IUD prior to removal (CDC [Curtis 2016a]).Virilization of the female fetus has been observed following exposure to the levonorgestrel IUD.Monitoring ParametersPrior to insertion: Assessment of pregnancy status; bimanual examination and cervical inspection; weight (optional; BMI at baseline may be helpful to monitor changes during therapy); STD screen (unless already screened according to CDC STD Treatment guidelines) (Curtis 2016a). Complete medical and social history which may determine conditions influencing an intrauterine device use for contraception.Following insertion: Transvagin*l ultrasound may be used to check placement. Changes in health status (including medications) should be assessed at routine follow-up visits (Curtis 2016a). Re-examine following insertion (4 to 6 weeks Kyleena, Liletta, Mirena, Skyla; 4 to 12 weeks Jaydess [Canadian product]) and then yearly or more frequently if necessary. Threads should be visible; if length of thread has changed, device may have become displaced, broken, perforated the uterus, or expelled. Monitor for significant changes in menstrual bleeding during prolonged use, Pap smear, blood pressure, serum glucose in patients with diabetes. Patients presenting with lower abdominal pain should be evaluated for ovarian cysts and ectopic pregnancy. Signs of infection. Monitor for signs/symptoms of thromboembolism in women who require surgery with prolonged immobilization.Reference RangeLiletta: Plasma concentrations range from a peak of 252 pg/mL (7 days following insertion) to 135 pg/mL (after 3 years).Mirena: Plasma concentrations range from 150 to 200 pg/mL.Skyla, Jaydess [Canadian product]: Plasma concentrations range from a peak of 192 pg/mL (2 days following insertion) to 59 to 61 pg/mL (after 3 years).Mechanism of ActionPregnancy may be prevented through several mechanisms: Thickening of cervical mucus, which inhibits sperm passage through the uterus; inhibition of sperm survival; alteration of the endometrium. Inhibition of ovulation may also occur in some patients.Pharmaco*kinetics (Adult data unless noted)Duration: Prevention of pregnancy: Kyleena: Up to 5 years; Liletta, Mirena: Up to 8 years; Skyla, Jaydess [Canadian product]: Up to 3 years.Distribution: Vd: ~1.8 L/kg.Protein binding: Highly bound to albumin (~50%) and sex hormone-binding globulin (~47%) (Fotherby 1995).Metabolism: Hepatic via CYP3A4; forms inactive metabolites.Excretion: Urine (~45%); feces (~32%).Pricing: USIntrauterine Device (Kyleena Intrauterine)19.5 mg (per each): $1,259.09Intrauterine Device (Liletta (52 MG) Intrauterine)20.1 mcg/day (per each): $1,014.12Intrauterine Device (Mirena (52 MG) Intrauterine)20 mcg/day (per each): $1,259.09Intrauterine Device (Skyla Intrauterine)13.5 mg (per each): $1,048.40Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalContraplan II (EG);Fleree (LV);Janess (IL);Jaydess (AU, BE, BG, CH, CZ, DK, FR, GB, IE, KR, MT, NZ, RO, SG, SI);Levosert (BG, GB, HR, LU, MT);Lovosert (LV);Mirena (AE, AT, AU, BB, BE, BH, BR, CH, CL, CN, CO, CZ, DE, DK, EC, EE, EG, ES, FI, FR, GB, GR, HK, HR, HU, ID, IE, IL, IS, IT, JO, JP, KR, KW, LK, LT, LU, LV, MT, MX, MY, NL, NO, NZ, PE, PH, PL, PT, PY, QA, RO, RU, SE, SG, SI, TH, TR, UA, VN, ZA)For country code abbreviations (show table)<800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 40-NF 35). Rockville, MD: United States Pharmacopeia Convention; 2017:83-102.Abu Hashim H, Ghayaty E, El Rakhawy M. Levonorgestrel-releasing intrauterine system vs oral progestins for non-atypical endometrial hyperplasia: a systematic review and metaanalysis of randomized trials. Am J Obstet Gynecol. 2015;213(4):469-478. doi:10.1016/j.ajog.2015.03.037 [PubMed 25797236]American College of Obstetricians and Gynecologists (ACOG) Committee on Adolescent Health Care. Committee Opinion No. 668: Menstrual manipulation for adolescents with physical and developmental disabilities. Obstet Gynecol. 2016;128(2):e20-e25. doi:10.1097/AOG.0000000000001585 [PubMed 27454732]American College of Obstetricians and Gynecologists (ACOG) Committee on Adolescent Health Care. Committee Opinion No. 817: Options for prevention and management of menstrual bleeding in adolescent patients undergoing cancer treatment. Obstet Gynecol. 2021;137(1):e7-e15. doi:10.1097/AOG.0000000000004209 [PubMed 33399429]American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Gynecology, Long-Acting Reversible Contraception Work Group. Practice bulletin no. 186: long-acting reversible contraception: implants and intrauterine devices. Obstet Gynecol. 2017;130(5):e251-e269. [PubMed 29064972]American College of Obstetricians and Gynecologists (ACOG) Committee Opinion No. 760: Dysmenorrhea and endometriosis in the adolescent. Obstet Gynecol. 2018;132(6):e249-e258. doi:10.1097/AOG.0000000000002978 [PubMed 30461694]American College of Obstetricians and Gynecologists (ACOG) Committee Opinion No. 631. Endometrial intraepithelial neoplasia. Obstet Gynecol. 2015;125(5):1272-1278. doi:10.1097/01.AOG.0000465189.50026.20 [PubMed 25932867]American College of Obstetricians and Gynecologists (ACOG) Committee Opinion No. 698: Hormone therapy in primary ovarian insufficiency. Obstet Gynecol. 2017;129(5):e134-e141. doi:10.1097/AOG.0000000000002044 [PubMed 28426619]Anthony MS, Reed SD, Armstrong MA, et al. Design of the Association of Uterine Perforation and Expulsion of Intrauterine Device study: a multisite retrospective cohort study. Am J Obstet Gynecol. 2021;224(6):599.e1-599.e18. doi:10.1016/j.ajog.2021.01.003 [PubMed 33460585]Armstrong AJ, Hurd WW, Elguero S, et al. Diagnosis and management of endometrial hyperplasia. J Minim Invasive Gynecol. 2012;19(5):562-571. doi:10.1016/j.jmig.2012.05.009 [PubMed 22863972]Averbach SH, Ermias Y, Jeng G, et al. Expulsion of intrauterine devices after postpartum placement by timing of placement, delivery type, and intrauterine device type: a systematic review and meta-analysis. Am J Obstet Gynecol. 2020;223(2):177-188. doi:10.1016/j.ajog.2020.02.045 [PubMed 32142826]Balayla J, Gil Y, Mattina J, Al-Shehri E, Ziegler C. Streptococcal toxic shock syndrome after insertion of a levonorgestrel intrauterine device. J Obstet Gynaecol Can. 2019;41(12):1772-1774. doi:10.1016/j.jogc.2019.02.017 [PubMed 30981616]Barnhart KT. Clinical practice. Ectopic pregnancy. N Engl J Med. 2009;361(4):379-387. doi:10.1056/NEJMcp0810384 [PubMed 19625718]Bonnington A, Dianat S, Kerns J, et al. Society of Family Planning clinical recommendations: contraceptive counseling for transgender and gender diverse people who were female sex assigned at birth. Contraception. 2020;102(2):70-82. doi:10.1016/j.contraception.2020.04.001 [PubMed 32304766]Caliskan E, Oztürk N, Dilbaz BO, Dilbaz S. Analysis of risk factors associated with uterine perforation by intrauterine devices. Eur J Contracept Reprod Health Care. 2003;8(3):150-155. [PubMed 14667326]Carvalho N, Margatho D, Cursino K, Benetti-Pinto CL, Bahamondes L. Control of endometriosis-associated pain with etonogestrel-releasing contraceptive implant and 52-mg levonorgestrel-releasing intrauterine system: randomized clinical trial. Fertil Steril. 2018;110(6):1129-1136. doi:10.1016/j.fertnstert.2018.07.003 [PubMed 30396557]Carvalho NM, Chou V, Modesto W, Margatho D, Garcia EAL, Bahamondes L. Relationship between user satisfaction with the levonorgestrel-releasing intrauterine system and bleeding patterns. J Obstet Gynaecol Res. 2017;43(11):1732-1737. doi:10.1111/jog.13441 [PubMed 28833891]Curtis KM, Jatlaoui TC, Tepper NK, et al. US selected practice recommendations for contraceptive use, 2016. MMWR Recomm Rep. 2016a;65(4):1‐66. doi:10.15585/mmwr.rr6504a1 [PubMed 27467319]Curtis KM, Tepper NK, Jatlaoui TC, et al. US medical eligibility criteria for contraceptive use, 2016. MMWR Recomm Rep. 2016b;65(3):1‐103. doi:10.15585/mmwr.rr6503a1 [PubMed 27467196]Darney PD, Stuart GS, Thomas MA, Cwiak C, Olariu A, Creinin MD. Amenorrhea rates and predictors during 1 year of levonorgestrel 52 mg intrauterine system use. Contraception. 2018;97(3):210-214. doi:10.1016/j.contraception.2017.10.005 [PubMed 29038072]de Jonge ET, Yigit R, Molenberghs G, Straetmans D, Ombelet W. Predictors of oligoamenorrhea at 1-year follow-up in premenopausal women using a levonorgestrel-releasing intrauterine system. Contraception. 2007;76(2):91-95. doi:10.1016/j.contraception.2007.04.003 [PubMed 17656176]Dolapcioglu K, Boz A, Baloglu A. The efficacy of intrauterine versus oral progestin for the treatment of endometrial hyperplasia. A prospective randomized comparative study. Clin Exp Obstet Gynecol. 2013;40(1):122-126. [PubMed 23724525]Ferguson CA, Costescu D, Jamieson MA, Jong L. Transmural migration and perforation of a levonorgestrel intrauterine system: a case report and review of the literature. Contraception. 2016;93(1):81-86. doi:10.1016/j.contraception.2015.08.019 [PubMed 26386445]Fotherby K. Levonorgestrel. Clinical pharmaco*kinetics. Clin Pharmaco*kinet. 1995;28(3):203-215. [PubMed 7758251]Frank ML, DiMaria C. Levonorgestrel Subdermal Implants. Drug Saf. 1997;17(6):360-368. [PubMed 9429835]Gaetani SL, Garbade GJ, Haas SI, Roth KR, Kane KE. A ruptured ectopic pregnancy in a patient with an intrauterine device: a case report. Radiol Case Rep. 2021;16(12):3672-3674. doi:10.1016/j.radcr.2021.08.074 [PubMed 34630798]Graner S, Mc Taggart J, Nordström F, Melander E, Widenberg J, Kopp Kallner H. Levonorgestrel intrauterine contraceptive systems (13.5 mg and 52 mg) and risk of ectopic pregnancy. Acta Obstet Gynecol Scand. 2019;98(7):937-943. doi:10.1111/aogs.13564 [PubMed 30737766]Gupta J, Kai J, Middleton L, et al. Levonorgestrel Intrauterine System versus Medical Therapy for Menorrhagia. N Engl J Med. 2013;368(2):128-137. [PubMed 23301731]Hardeman J, Weiss BD. Intrauterine devices: an update. Am Fam Physician. 2014;89(6):445-450. [PubMed 24695563]Heikkilä M, Haukkamaa M, Luukkainen T. Levonorgestrel in milk and plasma of breast-feeding women with a levonorgestrel-releasing IUD. Contraception. 1982;25(1):41-49. [PubMed 6800691]Heinemann K, Reed S, Moehner S, Minh TD. Risk of uterine perforation with levonorgestrel-releasing and copper intrauterine devices in the European Active Surveillance Study on Intrauterine Devices. Contraception. 2015;91(4):274-279. doi:10.1016/j.contraception.2015.01.007 [PubMed 25601352]Hopelian NG, Simmons RG, Sanders JN, et al. Comparison of levonorgestrel level and creamatocrit in milk following immediate versus delayed postpartum placement of the levonorgestrel IUD. BMC Womens Health. 2021;21(1):33. doi:10.1186/s12905-021-01179-7 [PubMed 33478494]Imai A, Matsunami K, Takagi H, Ichigo S. Levonorgestrel-releasing intrauterine device used for dysmenorrhea: five-year literature review. Clin Exp Obstet Gynecol. 2014;41(5):495-498. [PubMed 25864246]Jaydess (levonorgestrel) [product monograph]. Mississauga, Ontario, Canada: Bayer Inc; November 2018.Kaunitz AM, Inki P. The levonorgestrel-releasing intrauterine system in heavy menstrual bleeding: a benefit-risk review. Drugs. 2012;72(2):193-215. doi:10.2165/11598960-000000000-00000 [PubMed 22268392]Kirkham YA, Ornstein MP, Aggarwal A, McQuillan S. No. 313-Menstrual suppression in special circ*mstances. J Obstet Gynaecol Can. 2019;41(2):e7-e17. doi:10.1016/j.jogc.2018.11.030 [PubMed 30638562]Krempasky C, Harris M, Abern L, Grimstad F. Contraception across the transmasculine spectrum. Am J Obstet Gynecol. 2020;222(2):134-143. doi:10.1016/j.ajog.2019.07.043 [PubMed 31394072]Kyleena (levonorgestrel-releasing intrauterine system) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; July 2021.Kyleena (levonorgestrel) [product monograph]. Mississauga, Ontario, Canada: Bayer Inc; September 2021.Li C, Zhao WH, Meng CX, et al. Contraceptive use and the risk of ectopic pregnancy: a multi-center case-control study. PLoS One. 2014;9(12):e115031. Published December 10, 2014. doi:10.1371/journal.pone.0115031 [PubMed 25493939]Liletta (levonorgestrel) [prescribing information]. Irvine, CA: Allergan USA Inc; November 2022.Madden T, McNicholas C, Zhao Q, Secura GM, Eisenberg DL, Peipert JF. Association of age and parity with intrauterine device expulsion. Obstet Gynecol. 2014;124(4):718-726. doi:10.1097/AOG.0000000000000475 [PubMed 25198262]Makena D, Gichere I, Warfa K. Levonorgestrel intrauterine system embedded within tubal ectopic pregnancy: a case report. J Med Case Rep. 2021;15(1):107. doi:10.1186/s13256-021-02723-7 [PubMed 33685513]Margatho D, Carvalho NM, Bahamondes L. Endometriosis-associated pain scores and biomarkers in users of the etonogestrel-releasing subdermal implant or the 52-mg levonorgestrel-releasing intrauterine system for up to 24 months. Eur J Contracept Reprod Health Care. 2020;25(2):133-140. doi:10.1080/13625187.2020.1725461 [PubMed 32069126]Maybin JA, Critchley HO. Medical management of heavy menstrual bleeding. Womens Health (Lond). 2016;12(1):27-34. doi:10.2217/whe.15.100 [PubMed 26695687]McNicholas C, Maddipati R, Zhao Q, et al. Use of the etonogestrel implant and levonorgestrel intrauterine device beyond the U.S. Food and Drug Administration-approved duration. Obstet Gynecol. 2015;125(3):599-604. doi:10.1097/AOG.0000000000000690. [PubMed 25730221]Mirena (levonorgestrel) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; August 2022.Mirena (levonorgestrel) [product monograph]. Mississauga, Ontario, Canada: Bayer Inc; September 2021.Mittermeier T, Farrant C, Wise MR. Levonorgestrel-releasing intrauterine system for endometrial hyperplasia. Cochrane Database Syst Rev. 2020;9(9):CD012658. doi:10.1002/14651858.CD012658.pub2 [PubMed 32909630]Nowitzki KM, Hoimes ML, Chen B, Zheng LZ, Kim YH. Ultrasonography of intrauterine devices. Ultrasonography. 2015;34(3):183-194. doi:10.14366/usg.15010 [PubMed 25985959]Orbo A, Vereide A, Arnes M, et al. Levonorgestrel-impregnated intrauterine device as treatment for endometrial hyperplasia: a national multicentre randomised trial. BJOG. 2014;121(4):477-486. doi:10.1111/1471-0528.12499 [PubMed 24286192]Orme ML, Back DJ, Breckenridge AM. Clinical pharmaco*kinetics of oral contraceptive steroids. Clin Pharmaco*kinet. 1983;8(2):95-136. [PubMed 6342899]Plan B (levonorgestrel). Saint-Laurent, Quebec, Canada: Paladin Labs Inc; July 2014.Pradhan S, Gomez-Lobo V. Hormonal contraceptives, intrauterine devices, gonadotropin-releasing hormone analogues and testosterone: menstrual suppression in special adolescent populations. J Pediatr Adolesc Gynecol. 2019;32(5S):S23-S29. doi:10.1016/j.jpag.2019.04.007 [PubMed 30980941]Preshaw PM. Oral contraceptives and the periodontium. Peridontol 2000. 2013;61(1):125-159. [PubMed 23240947]Rowlands S, Oloto E, Horwell DH. Intrauterine devices and risk of uterine perforation: current perspectives. Open Access J Contracept. 2016;7:19-32. doi:10.2147/OAJC.S85546 [PubMed 29386934]Schreiber CA, Teal SB, Blumenthal PD, Keder LM, Olariu AI, Creinin MD. Bleeding patterns for the Liletta® levonorgestrel 52 mg intrauterine system. Eur J Contracept Reprod Health Care. 2018;23(2):116-120. doi:10.1080/13625187.2018.1449825 [PubMed 29560743]Shikary ZK, Betrabet SS, Patel ZM, et al, "ICMR Task Force Study on Hormonal Contraception. Transfer of Levonorgestrel (LNG) Administered Through Different Drug Delivery Systems from the Maternal Circulation into the Newborn Infant's Circulation via Breast Milk," Contraception, 1987, 35(5):477-86. [PubMed 3113823]Sitruk-Ware R and Nath A, "Metabolic Effects of Contraceptive Steroids," Rev Endocr Metab Disord, 2011, 12(2):63-75. [PubMed 21538049]Skyla (levonorgestrel-releasing intrauterine system) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; July 2021.Somboonp*rn W, Panna S, Temtanakitpaisan T, Kaewrudee S, Soontrapa S. Effects of the levonorgestrel-releasing intrauterine system plus estrogen therapy in perimenopausal and postmenopausal women: systematic review and meta-analysis. Menopause. 2011;18(10):1060-1066. doi:10.1097/gme.0b013e31821606c5 [PubMed 21720280]Trimble CL, Method M, Leitao M, et al. Management of endometrial precancers. Obstet Gynecol. 2012;120(5):1160-1175. doi:10.1097/AOG.0b013e31826bb121 [PubMed 23090535]Turok DK, Gero A, Simmons RG, et al. Levonorgestrel vs. copper intrauterine devices for emergency contraception. N Engl J Med. 2021;384(4):335-344. doi:10.1056/NEJMoa2022141 [PubMed 33503342]Turok DK, Leeman L, Sanders JN, et al. Immediate postpartum levonorgestrel intrauterine device insertion and breast-feeding outcomes: a noninferiority randomized controlled trial. Am J Obstet Gynecol. 2017;217(6):665.e1-665.e8. doi:10.1016/j.ajog.2017.08.003 [PubMed 28842126]US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. http://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf. Updated September 2016. Accessed October 5, 2016.Varila E, Wahlström T, Rauramo I. A 5-year follow-up study on the use of a levonorgestrel intrauterine system in women receiving hormone replacement therapy. Fertil Steril. 2001;76(5):969-973. doi:10.1016/s0015-0282(01)02846-1 [PubMed 11704119]Wildemeersch D, Janssens D, Schacht E, Pylyser K, de Wever N. Intrauterine levonorgestrel delivered by a frameless system, combined with systemic estrogen: acceptability and endometrial safety after 3 years of use in peri- and postmenopausal women. Gynecol Endocrinol. 2005;20(6):336-342. doi:10.1080/09513590500099156 [PubMed 16019384]Wildemeersch D, Pylyser K, De Wever N, Pauwels P, Tjalma W. Endometrial safety after 5 years of continuous combined transdermal estrogen and intrauterine levonorgestrel delivery for postmenopausal hormone substitution. Maturitas. 2007;57(2):205-209. doi:10.1016/j.maturitas.2006.11.010 [PubMed 17227699]Yucel N, Baskent E, Karamustafaoglu Balci B, Goynumer G. The levonorgestrel-releasing intrauterine system is associated with a reduction in dysmenorrhoea and dyspareunia, a decrease in CA 125 levels, and an increase in quality of life in women with suspected endometriosis. Aust N Z J Obstet Gynaecol. 2018;58(5):560-563. doi:10.1111/ajo.12773 [PubMed 29359457]Topic 127810 Version 67.0

Fertility awareness-based (FAB) methods for preventing pregnancy are based upon the physiologic changes during the menstrual cycle and the functional lifespan of sperm and ova. The patient is educated to understand when they are in their fertile period so they can then avoid vagin*l intercourse or u

Timely restoration of cerebral blood flow using reperfusion therapy is the most effective maneuver for salvaging ischemic brain tissue that is not already infarcted. There is a narrow window during which this can be accomplished since the benefit of reperfusion decreases over time.This topic will re

The most important factor in successful reperfusion therapy of acute ischemic stroke is early treatment. Nonetheless, selection of appropriate candidates for reperfusion demands a neurologic evaluation and a neuroimaging study. In addition, reperfusion therapy for acute stroke requires a system that

CloseOxycodone: Drug informationOxycodone: Drug information(For additional information see "Oxycodone: Patient drug information" and see "Oxycodone: Pediatric drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)ALERT: US Boxed WarningAddiction, abuse, and misuse:Oxycodone exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing oxycodone and monitor all patients regularly for the development of these behaviors or conditions.Opioid analgesic risk evaluation and mitigation strategy (REMS)To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the FDA has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to health care providers. Health care providers are strongly encouraged to complete a REMS-compliant education program and counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products; emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and consider other tools to improve patient, household, and community safety.Life-threatening respiratory depression:Serious, life-threatening, or fatal respiratory depression may occur with use of oxycodone. Monitor for respiratory depression, especially during initiation of oxycodone or following a dose increase. Instruct patients to swallow oxycodone tablets whole; crushing, chewing, or dissolving oxycodone ER tablets can cause rapid release and absorption of a potentially fatal dose of oxycodone.Accidental ingestion:Accidental ingestion of even one dose of oxycodone, especially by children, can result in a fatal overdose of oxycodone.Neonatal opioid withdrawal:Prolonged use of oxycodone during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.Cytochrome P450 3A4 interaction:The concomitant use of oxycodone with all cytochrome P450 (CYP-450) 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used CYP3A4 inducer may result in an increase in oxycodone plasma concentration. Monitor patients receiving oxycodone and any CYP3A4 inhibitor or inducer.Risks from concomitant use with benzodiazepines or other CNS depressants:Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of oxycodone and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.Risk of medication errors (oral solution):Ensure accuracy when prescribing, dispensing, and administering oxycodone oral solution. Dosing errors due to confusion between mg and mL, and other oxycodone oral solutions of different concentrations can result in accidental overdose.Brand Names: USOxaydo;OxyCONTIN;Roxicodone;RoxyBond;Xtampza ERBrand Names: CanadaACT Oxycodone CR [DSC];APO-Oxycodone CR;Oxy-IR;OxyNEO;PMS-OxyCODONE;PMS-OxyCODONE CR;Supeudol;Supeudol 10;Supeudol 20Pharmacologic CategoryAnalgesic, OpioidDosing: AdultNote: Place in therapy: When used for managing moderate to severe pain, opioids may be part of a comprehensive, multimodal, patient-specific treatment plan for pain. Maximize nonopioid analgesia, if appropriate, prior to initiation of opioid analgesia (Ref). Dose selection: Dosing provided is based on typical doses and some patients may require higher or lower doses. Individualize dosing and dosing intervals based on patient-specific factors (eg, comorbidities, severity of pain, concomitant medications, cachexia, general condition, degree of opioid experience/tolerance) and titrate to patient-specific treatment goals (eg, improvement in function and quality of life, decrease in pain using a validated pain rating scale). Use the lowest effective dose for the shortest period of time. Safety: Consider prescribing naloxone for patients with factors associated with an increased risk for overdose, such as history of overdose or substance use disorder, higher opioid dosages (≥50 morphine milligram equivalents [MME]/day orally [equivalent to ≥33 mg oxycodone/day]), and/or concomitant benzodiazepine use (Ref).Acute pain in opioid-naive patientsAcute pain in opioid-naive patients: General dosing: Note: For acute non–cancer-related pain severe enough to require an opioid, utilize multimodal pain control, maximize nonopioid analgesics, and limit the quantity prescribed to the expected duration of acute pain; a quantity sufficient for ≤3 days is often adequate, whereas >7 days is rarely needed. Do not use long-acting preparations for treatment of acute pain (Ref).Immediate release: Oral: Initial: 5 mg every 4 to 6 hours as needed; adjust dose according to patient response. Usual dosage range: 5 to 15 mg every 4 to 6 hours as needed. If usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies. For outpatient use, usually up to 20 mg/day for moderate pain or up to 30 mg/day for severe pain will suffice. Dosing is based on severity of pain and patient-specific factors; reduced dosing may be indicated in patients with comorbidities (Ref).Rectal [Canadian product]: Usual dosage range: One (10 or 20 mg) suppository up to 3 to 4 times daily as needed. If usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies (Ref).Acute pain in patients on chronic opioid therapyAcute pain (eg, breakthrough cancer pain) in patients on chronic opioid therapy:Immediate release: Oral: Usual dose: In conjunction with the scheduled opioid, administer 5% to 15% (rarely up to 20%) of the 24-hour oxycodone requirement (or MME) as needed using an IR formulation every 4 to 6 hours with subsequent dosage adjustments based upon response (Ref). Note: If chronic opioid is not oxycodone, use MME calculations cautiously due to lack of complete cross-tolerance; generally, reduce calculated dose by 25% to 50%; conversions from methadone are highly variable and require extreme caution (Ref).Acute postoperative pain, postoperative recovery/postanesthesia care unitAcute postoperative pain, postoperative recovery/postanesthesia care unit:Note: Optimize multimodal perioperative pain management (eg, regional or local anesthesia, nerve blocks, nonopioid analgesics, other adjuvants) to minimize opioid use (Ref). Refer to institutional protocols.Opioid-naive patients: Immediate release: Oral: Usual dosage range: 5 to 10 mg every 4 to 6 hours as needed. If usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies. Dosing is based on severity of pain and patient-specific factors; reduced dosing may be indicated in patients with comorbidities (Ref).Chronic pain, including chronic cancer painChronic pain, including chronic cancer pain:Note: Before starting opioid therapy for chronic pain, establish realistic goals for pain and function, and consider how therapy will be discontinued if benefits do not outweigh risks (Ref). Opioids, including oxycodone, are not the preferred therapy for chronic noncancer pain due to insufficient evidence of benefit and risk of serious harm; nonpharmacologic treatment and nonopioid analgesics are preferred, with the exception of chronic pain from active cancer, sickle cell disease, and end-of-life care. Consider opioids, including oxycodone, only in patients who experience clinically meaningful improvement in pain and function that outweighs patient safety risks (Ref).Opioid-naive patients: In general, for noncancer pain, establish oxycodone requirement using IR formulations (Ref). In patients with cancer pain, may switch to a long-acting formulation earlier in the course of therapy (Ref).Noncancer or cancer pain: Immediate release:Oral: Initial: 2.5 to 10 mg every 4 to 6 hours as needed or scheduled around the clock (eg, cancer pain); adjust dose according to patient response (see "Titration" below). Usual maintenance dosage range: 5 to 15 mg every 4 to 6 hours as needed or scheduled around the clock. If usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies. Dosing is based on severity of pain and patient-specific factors; start at the lower end of dosing range (Ref).Titration: Noncancer pain: Adjust dose according to patient response; if needed, increase the dose slowly in increments of no more than 25% to 50% of the total daily dose (Ref). Note: To reduce risk of overdose in noncancer pain (excluding patients with sickle cell disease and palliative care), use caution when increasing opioid dosage to ≥50 MME/day (equivalent to ≥33 mg oxycodone/day) and avoid increasing dosage to ≥90 MME/day (equivalent to ≥60 mg oxycodone/day) (Ref).Cancer pain: Adjust dose according to patient response; if needed, increase the fixed scheduled dose by 30% to 100% of the total dose taken in the prior 24-hour period including total amount of rescue medication used; if pain score decreased and functional assessment improved, continue current effective dosing (Ref).Rectal [Canadian product]: Usual dosage range: One (10 or 20 mg) suppository up to 3 to 4 times daily as needed. If usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies (Ref).Opioid-tolerant patients (also refer to "Dose Conversions for Pain Management"):Extended release: Note: Dosage forms: Dose of ER capsules is expressed as oxycodone base and dose of ER tablets is expressed as oxycodone hydrochloride; 9 mg of oxycodone base is equivalent to 10 mg oxycodone hydrochloride. Oxycodone ER capsules and ER tablets are not bioequivalent; monitor for changes in efficacy or tolerability and adjust dose if needed. Place in therapy: Although manufacturer's labeling contains directions for initiating ER oxycodone products in patients who are opioid-naive with chronic pain, these preparations should not be used as initial therapy. Instead, initiate treatment with an IR preparation to more accurately determine the daily opioid requirement and decrease the risk of overdose. Unless pain is associated with cancer, palliative care, or sickle cell disease, the CDC recommends that ER opioids be reserved for patients who have received IR opioids daily for ≥1 week yet continue to experience severe, continuous pain (Ref).ER tablet (oxycodone hydrochloride): Oral: See "Dose Conversions for Pain Management." Calculated dose may be administered every 12 hours.ER capsule (oxycodone base): Oral: See "Dose Conversions for Pain Management." Calculated dose may be administered every 12 hours. Maximum dose: 288 mg/day; safety of excipients in higher daily doses has not been established.Titration: After initiation of oxycodone ER, adjust dose in increments of 25% to 50% no more frequently than every 1 to 2 days until desired pain control. Patients may require rescue doses of an IR analgesic during dose titration. Observe for signs and symptoms of opioid withdrawal or signs of oversedation/toxicity; if unacceptable adverse reactions occur, reduce the dose. To reduce risk of overdose in noncancer pain (excluding patients with sickle cell disease and palliative care), use caution when increasing opioid dosage to ≥50 MME/day (equivalent to ≥33 mg oxycodone/day) and avoid increasing dosage to ≥90 MME/day (equivalent to ≥60 mg oxycodone/day) (Ref). Note: Some clinicians have reported better efficacy with more frequent dosing (ie, every 8 hours) (Ref); however, dosing more frequently than every 12 hours is not recommended by the manufacturer and safety has not been established.Dose conversions for pain management: Note: Equianalgesic conversions serve only as a general guide to estimate opioid dose equivalents for patients on scheduled doses of opioids. Multiple factors must be considered for safely individualizing conversion of opioid analgesia. In general, for noncancer pain, the decision to convert from an IR to an ER formulation should be individualized and reserved for those with severe continuous pain who have been taking opioids for ≥1 week (Ref).Converting from IR oxycodone to ER oxycodone preparations: Total daily oral oxycodone dose may be administered in 2 divided doses. Note: Dose of ER capsules is expressed as oxycodone base and the dose of ER tablets and IR formulations is expressed as oxycodone hydrochloride; 9 mg of oxycodone base is equivalent to 10 mg oxycodone hydrochloride.Converting between ER oxycodone preparations: Dose of ER capsules is expressed as oxycodone base and the dose of ER tablets is expressed as oxycodone hydrochloride; 9 mg of oxycodone base is equivalent to 10 mg oxycodone hydrochloride. Oxycodone ER capsules and ER tablets are not bioequivalent; monitor for changes in efficacy or tolerability and adjust dose if needed. Converting to/from oxycodone to/from a different opioid (parenteral or oral): Refer to published equianalgesic opioid conversion data (or institutional protocols) for guidance. Conversion ratios are only approximations and substantial interpatient variability exists; therefore, it is safer to underestimate a patient’s daily oral requirement and provide breakthrough pain relief with IR formulations than to risk overestimating daily requirements. When switching to a new opioid (except to/from methadone), reduce initial daily calculated equianalgesic dose of the new opioid by 25% to 50% to adjust for lack of complete mu receptor cross-tolerance (conversions to/from methadone are highly variable and require extreme caution) (Ref).Converting from transdermal fentanyl to oxycodone ER: Remove fentanyl patch at least 18 hours prior to starting oxycodone ER. The manufacturer suggests a conservative conversion approach of substituting each fentanyl 25 mcg/hour transdermal patch with 9 mg every 12 hours (oxycodone ER capsule) or 10 mg every 12 hours (oxycodone ER tablets). Systematic assessment of this suggested conversion has not been completed; monitor patients closely.Converting from methadone to oxycodone ER: Extreme caution and close monitoring is required when converting methadone to another opioid. Ratio between methadone and other opioid agonists varies widely according to previous dose exposure. Methadone has a long half-life and can accumulate in the plasma.Discontinuation or tapering of therapy: When reducing the dose, discontinuing, or tapering long-term opioid therapy, the dose should be gradually tapered. An optimal tapering schedule has not been established (Ref). Proposed schedules range from slow (eg, 10% reduction per week or 10% reduction per month depending on duration of long-term therapy) to rapid (eg, 25% to 50% reduction every few days) (Ref). Individualize dosing based on discussions with patient to minimize withdrawal while considering patient-specific goals and concerns, as well as the opioid’s pharmaco*kinetics. Slower tapers may be appropriate after long-term use (eg, years), particularly in the final stage of tapering, whereas more rapid tapers may be appropriate in patients experiencing severe adverse effects (Ref). During tapering, patients may be at an increased risk of overdose if they return to their original (or higher) opioid dose or use illicit opioids, due to rapid loss of tolerance; consider prescribing naloxone (Ref). Monitor carefully for signs/symptoms of withdrawal. If the patient displays withdrawal symptoms, consider slowing the taper schedule; alterations may include increasing the interval between dose reductions, decreasing amount of daily dose reduction, pausing the taper and restarting when the patient is ready, and/or coadministration of an alpha-2 agonist (eg, clonidine) to blunt withdrawal symptoms (Ref). Continue to offer nonopioid analgesics as needed for pain management during the taper; consider nonopioid adjunctive treatments for withdrawal symptoms (eg, GI symptoms, muscle spasm) as needed (Ref).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultThe renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.Note: There are no specific dose adjustments provided in the manufacturer's labeling. Oxycodone is excreted as parent drug (~10%) and as active to weakly active metabolites (~47%) with varying degrees of analgesic activity (Ref); half-life is prolonged and accumulation of active metabolites occurs in patients with kidney impairment (Ref). Use of other opioids may be preferred for management of severe pain in patients with kidney impairment (Ref).Note: When making dose adjustments for the rectal formulation [Canadian product], do not break, crush, cut, or dissolve the suppositories.Altered kidney function:CrCl ≥60 mL/minute: No dosage adjustment necessary.CrCl 30 to <60 mL/minute:Immediate release: Oral, rectal [Canadian product]: Initial: Administer 50% to 75% of usual dose no more frequently than every 6 hours (Ref). Use with caution; titrate gradually based on patient response and adverse effects.Extended release: Oral: Initial: Administer 50% to 75% of usual dose every 12 to 24 hours; if the reduced dose is less than smallest available dosage form, consider alternative analgesic. Use with caution; titrate gradually based on patient response and adverse effects (Ref).CrCl <30 mL/minute:Immediate release: Oral, rectal [Canadian product]: Initial: Administer 50% of usual dose no more frequently than every 8 hours. Use with caution; titrate gradually based on patient response and adverse effects (Ref).Extended release: Oral: ER formulations should preferably be avoided in patients with severe impairment (Ref).Hemodialysis, intermittent (thrice weekly): Slightly dialyzable (10.6%) (Ref):Immediate release: Oral, rectal [Canadian product]: Initial: Administer 50% of usual dose no more frequently than every 8 hours; titrate gradually based on patient response and adverse effects (Ref). Use with caution; cases of oxycodone toxicity have been reported in hemodialysis patients (Ref).Extended release: Oral: ER formulations should preferably be avoided in patients with severe impairment (Ref).Peritoneal dialysis:Immediate release: Oral, rectal [Canadian product]: Initial: Administer 50% of usual dose no more frequently than every 8 hours; titrate gradually based on patient response and adverse effects (Ref); use with caution.Extended release: Oral: ER formulations should preferably be avoided in patients with severe impairment (Ref).CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Close monitoring of response (analgesia) and adverse reactions (eg, sedation, CNS and respiratory depression) due to drug accumulation is important.Immediate release: Oral, rectal [Canadian product]: Initial: Administer 50% of usual dose no more frequently than every 6 hours; titrate gradually based on patient response and adverse effects (Ref).Extended release: Oral: Avoid use.PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response (analgesia) and adverse reactions (eg, sedation, CNS and respiratory depression) due to drug accumulation is important.Immediate release: Oral, rectal [Canadian product]: Initial: Administer 50% of usual dose no more frequently than every 6 hours; titrate gradually based on patient response and adverse effects (Ref).Extended release: Oral: Avoid use.Dosing: Hepatic Impairment: AdultImmediate release: Initiate therapy at 33% to 50% the usual dosage and titrate carefully. For patients with severe impairment, consider extending the dosing interval based on response and tolerability (eg, every 6 to 12 hours) (Ref).Extended release tablets or Extended release capsules: Initial: Initiate oxycodone ER with 33% to 50% of the calculated recommended dose. If reduced dose is less than smallest available dosage form consider alternative analgesic.Dosing: Pediatric(For additional information see "Oxycodone: Pediatric drug information")Note: Doses should be titrated to appropriate effect. Multiple concentrations of oral solution available (20 mg/mL and 1 mg/mL); the highly concentrated formulation (20 mg/mL) should only be used in opioid-tolerant patients (taking ≥30 mg/day of oxycodone or equivalent for ≥1 week). Orders for oxycodone oral solutions (20 mg/mL or 1 mg/mL) should be clearly written to include the intended dose (in mg not mL) and the intended product concentration to be dispensed to avoid potential dosing errors:Analgesia, moderate to severe painAnalgesia, moderate to severe pain: Limited data available:Infants ≤6 months: Immediate release: Oral solution (1 mg/mL): Oral: Initial dose: 0.025 to 0.05 mg/kg/dose every 4 to 6 hours as needed (Ref).Infants >6 months, Children, and Adolescents:Patient weight <50 kg: Immediate release: Oral: Initial dose: 0.1 to 0.2 mg/kg/dose every 4 to 6 hours as needed; for severe pain some experts have recommended an initial dose of 0.2 mg/kg; usual maximum dose range: 5 to 10 mg/dose (Ref).Patient weight ≥50 kg: Immediate release: Oral: Initial dose: 5 to 10 mg every 4 to 6 hours as needed; for severe pain an initial dose of 10 mg may be used; usual maximum dose: 20 mg/dose (Ref).Analgesia, severe pain requiring around-the-clock long-term opioid therapyAnalgesia, severe pain requiring around-the-clock long-term opioid therapy: Note: Use only in pediatric patients ≥11 years of age who are already receiving opioid therapy for ≥5 consecutive days, tolerating a minimum daily opioid dose of ≥20 mg of oxycodone orally or its equivalent at least for the 2 days immediately prior to starting extended-release oxycodone tablets, and for which alternative treatment options are inadequate. Prior to initiation, all other around-the-clock opioid therapy must be discontinued.Children ≥11 years and Adolescents: Extended-release tablets (eg, OxyContin): Oral:Initial dose: Based on current opioid regimen dose; use the following conversion factor table and equation to convert the current opioid(s) daily dose to the extended-release oxycodone tablet daily dose.Note: Substantial interpatient variability exists due to patient specific factors, relative potency of different opioids, and dosage forms; therefore, it is preferable to underestimate the initial 24-hour oral oxycodone requirements and utilize rescue medication (immediate-release opioid):Initial dose of extended-release oxycodone tablets every 12 hours = (mg/day of current opioid regimen X conversion factor)/2Dose calculations or adjustments for specific clinical scenarios:• If rounding is necessary, numerical value should be rounded down to the nearest tablet strength. If calculated daily dose is <20 mg, do not start extended-release oxycodone tablet as there is no safe tablet strength available.• If more than one opioid in the regimen, calculate the approximate extended-release oxycodone tablet dose for each opioid and sum the totals for the approximate total daily extended-release oxycodone tablet dose, then divide by 2 for the 12-hour extended-release oxycodone dose.• If current opioid regimen includes a fixed-dose opioid/nonopioid dosage form (eg, hydrocodone/acetaminophen), only the mg of opioid should be used in the conversion calculations.• If patient receiving concomitant CNS depressants, reduce extended-release oxycodone tablet starting dose by 1/3 to 1/2 the calculated initial dose.• If asymmetric dosing, the higher dose should be scheduled as the morning dose, and the lower dose 12 hours later.Note: The following conversion table should ONLY be used to convert opioid doses to extended-release oxycodone tablet (not from extended-release oxycodone tablet to other opioids; it is NOT a table of equianalgesic doses as it may overestimate initial dose).Conversion Factor for Calculating Initial Extended-Release Oxycodone Tablet Dose in Pediatric Patients ≥11 YearsCurrent opioid regimen to be converted to extended-release oxycodone tabletConversion factorOralParenteralaOxycodone1--Hydrocodone0.9--Hydromorphone420Morphine0.53Tramadol0.170.2a For patients receiving high-dose parenteral opioids, a more conservative conversion factor should be applied (ie, lower numerical conversion factor); for example, for high-dose parenteral morphine, a conversion of 1.5 should be used for calculations instead of 3.Conversion from fentanyl patch to extended-release oxycodone tablet: Limited data available: Children ≥11 years and Adolescents: Note: Remove fentanyl patch ≥18 hours prior to starting extended-release oxycodone. Initial dose based on current opioid regimen dose; the manufacturer suggests using the conservative conversion factor of 10 mg every 12 hours of extended-release oxycodone tablet for each 25 mcg/hour fentanyl transdermal patch; systemic assessment of this suggested conversion has not been completed, monitor patients closely.Maintenance dose: Dosage adjustment (titration): After initiation of extended-release oxycodone tablet, adjust dose in small increments (up to 25% of current total daily dosage) no more frequently than every 1 to 2 days until desired pain control; patients may require rescue doses of an immediate-release analgesic during dose titration. Observe for signs and symptoms of opioid withdrawal or signs of oversedation/toxicity; if unacceptable adverse reactions occur, the subsequent dose may be reduced.Discontinuation of therapy: When discontinuing chronic opioid therapy, the dose should be gradually tapered down. An optimal universal tapering schedule for all patients has not been established (Ref). Specific pediatric protocols are lacking; based on experience in adults, proposed schedules range from slow (eg, 10% reductions per week) to rapid (eg, 25% to 50% reduction every few days) (Ref). Tapering schedules should be individualized to minimize opioid withdrawal while considering patient-specific goals and concerns as well as the pharmaco*kinetics of the opioid being tapered. An even slower taper may be appropriate in patients who have been receiving opioids for a long duration (eg, years), particularly in the final stage of tapering, whereas more rapid tapers may be appropriate in patients experiencing severe adverse events (Ref). Monitor carefully for signs/symptoms of withdrawal. If the patient displays withdrawal symptoms, consider slowing the taper schedule; alterations may include increasing the interval between dose reductions, decreasing amount of daily dose reduction, or pausing the taper and restarting when the patient is ready (Ref). Continue to offer nonopioid analgesics as needed for pain management during the taper; consider nonopioid adjunctive treatments for withdrawal symptoms.Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricIn general, oxycodone clearance may be decreased in patients with renal impairment; initiate therapy at low end of dosing range.Immediate release: Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, the following adjustments have been recommended (Ref):GFR ≥50 mL/minute/1.73 m2: No dosage adjustment required.GFR 10 to 50 mL/minute/1.73 m2: Administer 75% of dose.GFR <10 mL/minute/1.73 m2: Administer 50% of dose.Hemodialysis: Administer 50% of dose posthemodialysis.Peritoneal dialysis: Administer 50% of dose.Extended-release tablets (eg, OxyContin): Children ≥11 years and Adolescents: CrCl <60 mL/minute: Serum concentrations are increased ~50%. Initiate at the low end of the dosage range (use caution); adjust dose as clinically indicated. Doses of 33% to 50% of usual initial dosing have been recommended; if the reduced dose is less than smallest available dosage form, consider alternative analgesic.Dosing: Hepatic Impairment: PediatricImmediate release: There are no dosage adjustments provided in the manufacturer's labeling; based on experience in adult patients, may consider a conservative approach of reduced initial doses; adjust dose based on clinical response.Extended-release tablets (eg, OxyContin): Children ≥11 years and Adolescents: Initial: One-third (1/3) to one-half (1/2) of the usual starting dose; carefully titrate dose to appropriate effect. If reduced dose is less than smallest available dosage form, consider alternative analgesic.Dosing: Older AdultRefer to adult dosing. Initiate therapy at low end of dosing range and use caution.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.[DSC] = Discontinued productCapsule, Oral, as hydrochloride: Generic: 5 mgCapsule ER 12 Hour Abuse-Deterrent, Oral: Xtampza ER: 9 mg (100 ea); 13.5 mg (100 ea); 18 mg (100 ea); 27 mg (100 ea); 36 mg (100 ea)Concentrate, Oral, as hydrochloride: Generic: 100 mg/5 mL (30 mL)Solution, Oral, as hydrochloride: Generic: 5 mg/5 mL (5 mL, 15 mL, 473 mL, 500 mL)Tablet, Oral, as hydrochloride: Oxaydo: 5 mg, 7.5 mgRoxicodone: 5 mg [DSC] [scored]Roxicodone: 15 mg [scored; contains fd&c blue #2 (indigotine), quinoline yellow (d&c yellow #10)]Roxicodone: 30 mg [scored]Generic: 5 mg, 10 mg, 15 mg, 20 mg, 30 mgTablet Abuse-Deterrent, Oral: RoxyBond: 15 mg, 30 mg [contains fd&c blue #2 (indigotine)]Tablet Abuse-Deterrent, Oral, as hydrochloride: RoxyBond: 5 mgTablet ER 12 Hour Abuse-Deterrent, Oral, as hydrochloride: OxyCONTIN: 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mgOxyCONTIN: 80 mg [contains fd&c blue #2 (indigo carm) aluminum lake]Generic: 10 mg, 15 mg [DSC], 20 mg, 30 mg [DSC], 40 mg, 60 mg [DSC], 80 mgGeneric Equivalent Available: USMay be product dependentDosage Forms ConsiderationsXtampza ER: Strength is expressed in terms of oxycodone base.9 mg equivalent to 10 mg oxycodone hydrochloride13.5 mg equivalent to 15 mg oxycodone hydrochloride18 mg equivalent to 20 mg oxycodone hydrochloride27 mg equivalent to 30 mg oxycodone hydrochloride36 mg equivalent to 40 mg oxycodone hydrochlorideDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Suppository, Rectal: Supeudol 10: 10 mg (12 ea)Supeudol 20: 20 mg (12 ea)Tablet, Oral, as hydrochloride: Oxy-IR: 5 mg, 10 mg, 20 mgSupeudol: 5 mg, 10 mg, 20 mgGeneric: 5 mg, 10 mg, 20 mgTablet ER 12 Hour Abuse-Deterrent, Oral, as hydrochloride: OxyNEO: 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mgOxyNEO: 80 mg [contains fd&c blue #2 (indigo carm) aluminum lake]Tablet Extended Release 12 Hour, Oral: Generic: 5 mg, 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, 80 mgControlled SubstanceC-IIMedication Guide and/or Vaccine Information Statement (VIS)An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:Oxaydo: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202080s012lbl.pdf#page=30Oxycodone hydrochloride capsules: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/200534s011lbl.pdf#page=30Oxycodone hydrochloride oral solution: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/201194s009lbl.pdf#page=33OxyContin: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/022272s046lbl.pdf#page=48Roxybond: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/209777s007lbl.pdf#page=39Roxicodone: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021011s011lbl.pdf#page=30Xtampza ER: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208090s015lbl.pdf#page=39Administration: AdultAppropriate laxatives should be administered to avoid the constipating side effects associated with use. Antiemetics may be needed for persistent nausea. Some dosage forms (eg, ER) may not be appropriate for administration through feeding tubes (eg, gastric, NG). Refer to product labeling.ER dosage forms:Oral: Tablet: Administer with or without food. Swallow tablet whole. Do not moisten, dissolve, cut, crush, break, or chew extended release tablets. Extended release tablets should be administered one at a time and each followed with water immediately after placing in the mouth.Capsule: Administer each dose with food and approximately the same amount. For patients with difficulty swallowing, capsule may be opened and the contents sprinkled on soft foods (eg, applesauce, pudding, yogurt, ice cream, jam) or into a cup for administration directly into the mouth. Rinse mouth immediately afterwards to ensure all contents have been swallowed. Contents of capsule may also be administered through a nasogastric (NG) tube or gastrostomy tube (G-tube). Flush tube with water first, then pour capsule contents directly into tube (do not premix capsule contents with fluid that will be used to flush them through the tube). After contents have been placed in tube, flush tube with 15 mL of water, milk, or liquid nutritional supplement once and then repeat twice with 10 mL.Bariatric surgery: Tablet, abuse deterrent and extended or controlled release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Roxybond (oxycodone) tablets are formulated to have increased resistance to cutting, crushing, grinding, or breaking. Pharmaco*kinetics are similar to other IR oxycodone formulations. Nonabuse-deterrent IR tablet, capsule, and oral solution formulations are available. Oxycodone ER capsule contents may be taken by sprinkling the contents onto soft food (ie, applesauce, ice cream, yogurt). If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, clinicians should be advised that oral morphine has been shown to have significantly increased Cmax and decreased Tmax in the immediate (1 to 2 weeks) and long-term (6-months) period after bariatric surgery.IR dosage forms:Oral:Capsule: Administer with or without food.Oral solution: Administer with or without food. Available in two strengths; 1 mg/mL and a concentrated oral solution (20 mg/mL). Precautions should be taken to avoid confusion between the different concentrations; prescriptions should have the concentration specified as well as the dose clearly represented as milligram (mg) of oxycodone, not volume (mL). The enclosed calibrated oral syringe should always be used to administer the concentrated oral solution to ensure the dose is measured and administered accurately. The concentrated oral solution (20 mg/mL) may be used in opioid-tolerant patients (taking ≥30 mg/day of oxycodone or equivalent for ≥1 week); may also be used in palliative care patients who have difficulty and/or are unable to swallow. The concentrate is not substantially absorbed sublingually/orally and requires the GI tract for effective absorption (Ref).Tablets:Without abuse deterrent: Administer with or without food. When administered with food, onset may be delayed.With abuse deterrent:Oxaydo: Administer with or without food. Do not crush, chew, or dissolve the tablets. Due to inactive ingredient that causes nasal burning (upon snorting) and throat irritation, the tablet must be swallowed whole with enough water to ensure complete swallowing immediately after placing in the mouth. The tablet should not be wet prior to placing in the mouth.Rectal:Suppository [Canadian product]: Administer rectally. Do not break, crush, cut, or dissolve the suppositories.Administration: PediatricOral:Immediate release (capsule, oral solution, tablets): May administer with food to decrease GI upset:Oral solution: Available in 2 strengths: 1 mg/mL and a concentrated oral solution (20 mg/mL). Precautions should be taken to avoid confusion between the different concentrations; prescriptions should have the concentration specified as well as the dose clearly represented as milligram (mg) of oxycodone, not volume (mL). The enclosed calibrated oral syringe should always be used to administer the concentrated oral solution to ensure the dose is measured and administered accurately. The concentrated oral solution (20 mg/mL) should only be used in opioid-tolerant patients (taking ≥30 mg/day of oxycodone or equivalent for ≥1 week).Tablet (Oxaydo): Swallow whole with adequate water to ensure complete swallowing immediately after placing in the mouth; the formulation uses technology designed to discourage common methods of tampering to prevent misuse/abuse. The tablet should not be wet prior to placing in the mouth. Do not crush, chew, or dissolve nor administer via feeding tubes (eg, gastric, NG) due to potential for obstruction.Extended release: Tablet (eg, OxyContin): May administer with food to decrease GI upset. Swallow whole; do not moisten, dissolve, cut, crush, chew, or break as this would result in rapid release of oxycodone and absorption of a potentially fatal dose of drug. Administer one at a time and follow each with water immediately after placing in the mouth. For oral use only; do not administer rectally; increased risk of adverse events due to better rectal absorption.Use: Labeled IndicationsPain management:Immediate release: Management of acute or chronic moderate to severe pain when the use of an opioid analgesic is appropriate and for which alternative treatments are inadequate.Extended release:Capsules (Xtampza ER): Management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate in adults.Tablets (Oxycontin): Management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate in adults and opioid-tolerant pediatric patients ≥11 years of age who are already receiving and tolerating a minimum daily opioid dose of at least 20 mg oxycodone orally or its equivalent.Medication Safety IssuesSound-alike/look-alike issues:OxyCODONE may be confused with HYDROcodone, oxybutynin, OxyCONTIN, oxyMORphoneOxyCONTIN may be confused with MS Contin, oxybutynin, oxyMORphoneOxyFast may be confused with RoxanolRoxicodone may be confused with RoxanolHigh alert medication:The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. As reported with adult patients, unless otherwise noted.>10%:Central nervous system: Drowsiness (extended-release: 9% to 23%, extended-release, adolescents: 1% to <5%; immediate-release: ≥3%), headache (extended-release: 14%; immediate-release: ≥3%), dizziness (extended-release: 2% to 13%; immediate-release: ≥3%)Dermatologic: Pruritus (extended-release: 3% to 13%; immediate-release: ≥3%)Gastrointestinal: Nausea (extended-release: 11% to 23%; immediate-release: ≥3%), constipation (extended-release: 5% to 23%; extended-release, adolescents: 9%; immediate-release: ≥3%), vomiting (extended-release: 4% to 21%; immediate-release: 3%)Miscellaneous: Fever (extended-release: 1% to 11%; immediate-release: ≥3%)1% to 10%:Cardiovascular: Flushing (extended-release: 1% to 5%), hypertension (extended-release: 1% to 5%), orthostatic hypotension (extended-release: 1% to 5%), oxygen saturation decreased (extended-release, adolescents: 1% to <5%), edema (immediate-release: ≤5%; extended-release: <1%), tachycardia (<5%), cardiac failure (immediate-release: <3%), deep vein thrombosis (immediate-release: <3%), hypotension (<3%), palpitations (<3%; may occur with withdrawal), peripheral edema (immediate-release: <3%; extended-release: <1%), thrombophlebitis (immediate-release: <3%), vasodilation (<3%)Central nervous system: Abnormality in thinking (extended-release: 1% to 5%), dysphoria (extended-release: 1% to 5%), insomnia (1% to 5%), irritability (extended-release: 1% to 5%), twitching (extended-release: 1% to 5%), abnormal dreams (extended-release: ≤5%), anxiety (≤5%), chills (≤5%), confusion (≤5%), euphoria (extended-release: ≤5%), fatigue (extended-release: ≤5%), hypoesthesia (≤5%), migraine (≤5%), nervousness (≤5%), withdrawal syndrome (extended-release: ≤5%), agitation (<5%), pain (<5%), depression (extended-release, adolescents: 1% to <5%; extended-release, adults: <1%), lethargy (adolescents: 1% to <5%; extended-release, adults: <1%), paresthesia (extended-release, adolescents: 1% to <5%; extended-release, adults: <1%), procedural pain (extended-release, adolescents: 1% to <5%), hypertonia (<3%), neuralgia (<3%), personality disorder (immediate-release: <3%)Dermatologic: Excoriation (extended-release: 1% to 5%), diaphoresis (≤5%), hyperhidrosis (≤5%), skin rash (≤5%), skin photosensitivity (immediate-release: <3%), urticaria (<3%)Endocrine & metabolic: Hypochloremia (extended-release, adolescents: 1% to <5%), hyponatremia (extended-release: 1% to <5%), weight loss (extended-release, adolescents: 1% to <5%), hyperglycemia (≤5%), gout (immediate-release: <3%)Gastrointestinal: Diarrhea (≤6%), xerostomia (≤6%), gastritis (extended-release: 1% to 5%), hiccups (extended-release: 1% to 5%), upper abdominal pain (extended-release: 1% to 5%), abdominal pain (≤5%), anorexia (≤5%), decreased appetite (≤5%), dyspepsia (≤5%), gastroesophageal reflux disease (extended-release: ≤5%), dysphagia (immediate-release: <3%; extended-release: <1%), gingivitis (immediate-release: <3%), glossitis (immediate-release: <3%)Genitourinary: Dysuria (extended-release, adolescents: 1% to <5%; extended-release, adults: <1%), urinary retention (extended-release, adolescents: 1% to <5%; extended-release, adults: <1%), urinary tract infection (immediate-release: <3%)Hematologic & oncologic: Decreased hemoglobin (extended-release, adolescents: 1% to <5%), decreased platelet count (extended-release, adolescents: 1% to <5%), decreased red blood cells (extended-release, adolescents: 1% to <5%), febrile neutropenia (extended-release, adolescents: 1% to <5%), neutropenia (extended-release, adolescents: 1% to <5%), anemia (immediate-release: <3%), hemorrhage (immediate-release: <3%), iron deficiency anemia (immediate-release: <3%), leukopenia (immediate-release: <3%)Hepatic: Increased serum alanine aminotransferase (extended-release, adolescents: 1% to <5%)Hypersensitivity: Hypersensitivity reaction (<3%)Infection: Herpes simplex infection (immediate-release: <3%), infection (immediate-release: <3%), sepsis (immediate-release: <3%)Neuromuscular & skeletal: Asthenia (1% to 6%), limb pain (extended-release, adolescents: 1% to <5%), arthralgia (≤5%), back pain (≤5%), musculoskeletal pain (extended release: ≤5%), myalgia (≤5%), tremor (≤5%), arthritis (immediate-release: <3%), laryngospasm (immediate-release: <3%), neck pain (immediate-release: <3%), ostealgia (immediate-release: <3%), pathological fracture (immediate-release: <3%)Ophthalmic: Blurred vision (extended-release: 1% to 5%), amblyopia (immediate-release: <3%)Respiratory: Cough (≤5%), dyspnea (≤5%), oropharyngeal pain (extended-release: ≤5%), bronchitis (immediate-release: <3%), epistaxis (immediate-release: <3%), flu-like symptoms (immediate-release: <3%), laryngismus (immediate-release: <3%), pharyngitis (immediate-release: <3%), pulmonary disease (immediate-release: <3%), rhinitis (immediate-release: <3%), sinusitis (immediate-release: <3%)Miscellaneous: Seroma (extended-release, adolescents: 1% to <5%), accidental injury (<3%; extended-release: <1%)Frequency not defined:Cardiovascular: Circulatory depression, shockCentral nervous system: DepersonalizationRespiratory: Respiratory depression<1%, postmarketing, and/or case reports: Abnormal gait, aggressive behavior, amenorrhea, amnesia, chest pain, choking sensation, cholestasis, dehydration, dental caries, depression of ST segment on ECG, diverticulitis of the gastrointestinal tract (exacerbation), drug abuse, drug dependence, drug overdose (may be intentional), dysgeusia, emotional lability, eructation, exfoliative dermatitis, facial edema, flatulence, gag reflex, gastrointestinal disease, hallucination, hematuria, hyperalgesia, hyperkinesia, hypogonadism, hypotonia, impotence, increased appetite, increased gamma-glutamyl transferase, increased heart rate, increased liver enzymes, increased thirst, intestinal obstruction, lymphadenopathy, malaise, memory impairment, mood changes, neonatal withdrawal, night sweats, pharyngeal edema, polyuria, restlessness, seizure, SIADH, sleep disturbance, speech disturbance, stomatitis, stupor, suicidal ideation, suicidal tendencies, syncope, tinnitus, vertigo, visual disturbance, voice disorder, xerodermaContraindicationsHypersensitivity (eg, anaphylaxis, angioedema) to oxycodone or any component of the formulation; significant respiratory depression; hypercapnia; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; GI obstruction, including paralytic ileus (known or suspected).Documentation of allergenic cross-reactivity for opioids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to other opioids; suspected surgical abdomen (eg, acute appendicitis or pancreatitis); any disease/condition that affects bowel transit; mild pain that can be managed with other pain medications (immediate release, suppository); mild, intermittent or short duration pain that can be managed with other pain medications or acute pain (extended release); chronic obstructive airway; status asthmaticus; cor pulmonale; acute alcoholism; delirium tremens; convulsive disorders; severe CNS depression; increased cerebrospinal or intracranial pressure; head injury; monoamine oxidase (MAO) inhibitors (concomitant use or within 14 days of therapy); pregnant women or during labor and delivery; breastfeeding.Warnings/PrecautionsConcerns related to adverse effects:• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).• Constipation: May cause constipation, which may be problematic in patients with unstable angina and patients post-myocardial infarction (MI). Consider preventive measures (eg, stool softener, increased fiber) to reduce the potential for constipation.• Hypotension: May cause severe hypotension (including orthostatic hypotension and syncope); use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs that may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration. Avoid use in patients with circulatory shock.• Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (codeine, hydrocodone, hydromorphone, levorphanol, oxymorphone).• Respiratory depression: [US Boxed Warning]: Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely for respiratory depression, especially during initiation or dose escalation. Swallow ER tablets whole; crushing, chewing, or dissolving can cause rapid release and a potentially fatal dose. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. Patients and caregivers should be educated on how to recognize respiratory depression and the importance of getting emergency assistance immediately (eg, calling 911) in the event of known or suspected overdose.Disease-related concerns:• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.• Adrenocortical insufficiency: Use with caution in patients with adrenocortical insufficiency, including Addison disease; dose adjustment may be required. Long-term opioid use may cause secondary hypogonadism, which may lead to mood disorders and osteoporosis (Brennan 2013).• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; may cause constriction of sphincter of Oddi.• CNS depression/coma: Avoid use in patients with impaired consciousness or coma as these patients are susceptible to intracranial effects of CO2 retention.• Delirium tremens: Use with caution in patients with delirium tremens.• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur.• Hepatic impairment: Use with caution in patients with hepatic impairment; oxycodone clearance may decrease.• Mental health conditions: Use opioids with caution for chronic pain in patients with mental health conditions (eg, depression, anxiety disorders, post-traumatic stress disorder) due to increased risk for opioid use disorder and overdose; more frequent monitoring is recommended (Dowell [CDC 2016]).• Obesity: Use with caution in patients who are morbidly obese.• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture; dose adjustment may be required.• Psychosis: Use with caution in patients with toxic psychosis.• Renal impairment: Use with caution in patients with renal impairment; oxycodone clearance may decrease.• Respiratory disease: Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression, particularly when initiating and titrating therapy; critical respiratory depression may occur, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.• Seizures: Use with caution in patients with a history of seizure disorders; may cause or exacerbate preexisting seizures.• Sleep-related disorders: Opioid use increases the risk for sleep-related disorders (eg, central sleep apnea [CSA], hypoxemia) in a dose-dependent fashion. Use with caution for chronic pain and titrate dosage cautiously in patients with risk factors for sleep-disordered breathing (eg, heart failure, obesity). Consider dose reduction in patients presenting with CSA. Avoid opioids in patients with moderate to severe sleep-disordered breathing (Dowell [CDC 2016]).• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.Concurrent drug therapy issues:• Benzodiazepines or other CNS depressants: [US Boxed Warning]: Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of oxycodone and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosage and durations to the minimum required and follow patients for signs and symptoms of respiratory depression and sedation. Consider prescribing naloxone for emergency treatment of opioid overdose in patients taking benzodiazepines or other CNS depressants concomitantly with opioids.• CYP 3A4 interactions: [US Boxed Warning]: Use with all CYP3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitant CYP 3A4 inducer may result in increased oxycodone concentrations. Monitor patients receiving oxycodone and any CYP 3A4 inhibitor or inducer. Special populations:• Cachectic or debilitated patients: Use with caution in cachectic or debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Dose reduction may be required. Consider the use of alternative nonopioid analgesics in these patients.• Older adult: Use with caution in elderly patients; may be more sensitive to adverse effects. Use opioids for chronic pain with caution in this age group; monitor closely due to an increased potential for risks, including certain risks such as falls/fracture, cognitive impairment, and constipation. Clearance may also be reduced in older adults (with or without renal impairment) resulting in a narrow therapeutic window and increasing the risk for respiratory depression or overdose (Dowell [CDC 2016]). Consider the use of alternative nonopioid analgesics in these patients.• Neonates: Neonatal withdrawal syndrome: [US Boxed Warning]: Prolonged use of opioids during pregnancy can cause neonatal withdrawal syndrome, which may be life-threatening if not recognized and treated according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. Signs and symptoms include irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration and severity depend on the drug used, duration of use, maternal dose, and rate of drug elimination by the newborn.Dosage form specific issues:• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggest that benzoate displaces bilirubin from protein-binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.• Extended-release tablets: Tablets may be difficult to swallow and could become lodged in throat; patients with swallowing difficulties may be at increased risk. Cases of intestinal obstruction or diverticulitis exacerbation have also been reported, including cases requiring medical intervention to remove the tablet; patients with an underlying GI disease (eg, esophageal cancer, colon cancer) may be at increased risk.• Oral solutions:[US Boxed Warning]: Ensure accuracy when prescribing, dispensing, and administering oxycodone oral solution. Dosing errors due to confusion between mg and mL, and other oxycodone oral solutions of different concentrations can result in accidental overdose.Other warnings/precautions:• Abrupt discontinuation/withdrawal: Abrupt discontinuation in patients who are physically dependent on opioids has been associated with serious withdrawal symptoms, uncontrolled pain, attempts to find other opioids (including illicit), and suicide. Use a collaborative, patient-specific taper schedule that minimizes the risk of withdrawal, considering factors such as current opioid dose, duration of use, type of pain, and physical and psychological factors. Monitor pain control, withdrawal symptoms, mood changes, suicidal ideation, and for use of other substances and provide care as needed. Concurrent use of mixed agonist/antagonist analgesics (eg, pentazocine, nalbuphine, butorphanol) or partial agonist (eg, buprenorphine) analgesics may also precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists.• Abuse/misuse/diversion: [US Boxed Warning]: Use exposes patients and other users to the risks of addiction, abuse, and misuse, potentially leading to overdose and death. Assess each patient's risk prior to prescribing; monitor all patients regularly for development of these behaviors or conditions. Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Other factors associated with increased risk for misuse include younger age, concomitant depression (major), and psychotropic medication use. Consider offering naloxone prescriptions in patients with factors associated with an increased risk for overdose, such as history of overdose or substance use disorder, higher opioid dosages (≥50 morphine milligram equivalents [MME]/day orally), and concomitant benzodiazepine use (Dowell [CDC 2016]).• Accidental exposure: [US Boxed Warning]: Accidental ingestion of even one dose, especially in children, can result in a fatal overdose of oxycodone.• Appropriate use: Chronic pain (outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-based opioid use disorder treatment) in outpatient setting in adults: Opioids should not be used as first-line therapy for chronic pain management (pain >3-month duration or beyond time of normal tissue healing) due to limited short-term benefits, undetermined long-term benefits, and association with serious risks (eg, overdose, MI, auto accidents, risk of developing opioid use disorder). Preferred management includes nonpharmacologic therapy and nonopioid therapy (eg, nonsteroidal anti-inflammatory drugs, acetaminophen, certain antiseizure medications and antidepressants). If opioid therapy is initiated, it should be combined with nonpharmacologic and non-opioid therapy, as appropriate. Prior to initiation, known risks of opioid therapy should be discussed and realistic treatment goals for pain/function should be established, including consideration for discontinuation if benefits do not outweigh risks. Therapy should be continued only if clinically meaningful improvement in pain/function outweighs risks. Therapy should be initiated at the lowest effective dosage using IR opioids (instead of ER/long-acting opioids). Risk associated with use increases with higher opioid dosages. Risks and benefits should be re-evaluated when increasing dosage to ≥50 MME/day orally; dosages ≥90 MME/day orally should be avoided unless carefully justified (Dowell [CDC 2016]).• Naloxone access: Discuss the availability of naloxone with all patients who are prescribed opioid analgesics, as well as their caregivers, and consider prescribing it to patients who are at increased risk of opioid overdose. These include patients who are also taking benzodiazepines or other CNS depressants, have an opioid use disorder (OUD) (current or history of), or have experienced a previous opioid overdose. Additionally, health care providers should consider prescribing naloxone to patients prescribed medications to treat OUD; patients at risk of opioid overdose even if they are not taking an opioid analgesic or medication to treat OUD; and patients taking opioids, including methadone or buprenorphine for OUD, if they have household members, including children, or other close contacts at risk for accidental ingestion or opioid overdose. Inform patients and caregivers on options for obtaining naloxone (eg, by prescription, directly from a pharmacist, a community-based program) as permitted by state dispensing and prescribing guidelines. Educate patients and caregivers on how to recognize respiratory depression, proper administration of naloxone, and getting emergency help.• Optimal regimen: An opioid-containing analgesic regimen should be tailored to each patient's needs and based upon the type of pain being treated (acute versus chronic), the route of administration, degree of tolerance for opioids (naive versus chronic user), age, weight, and medical condition. The optimal analgesic dose varies widely among patients; doses should be titrated to pain relief/prevention.• REMS program: [US Boxed Warning]: To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, a REMS is required. Drug companies with approved opioid analgesic products must make REMS-compliant education programs available to health care providers. Health care providers are encouraged to complete a REMS-compliant education program; counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products; emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist; and consider other tools to improve patient, household, and community safety.• Surgery: Opioids decrease bowel motility; monitor for decreased bowel motility in postop patients receiving opioids. Use with caution in the perioperative setting; individualize treatment when transitioning from parenteral to oral analgesics.Metabolism/Transport EffectsSubstrate of CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potentialDrug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyAlvimopan: Opioid Agonists may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation.Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modificationAmphetamines: May enhance the analgesic effect of Opioid Agonists. Risk C: Monitor therapyAnticholinergic Agents: May enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor therapyAzelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combinationBlonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin.Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modificationBrimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyBromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyBromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combinationCannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products.Risk C: Monitor therapyChlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modificationChlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapyClofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapyCNS Depressants: May enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modificationCYP3A4 Inducers (Moderate): May decrease the serum concentration of OxyCODONE. Risk C: Monitor therapyCYP3A4 Inducers (Strong): May decrease the serum concentration of OxyCODONE. Risk C: Monitor therapyCYP3A4 Inhibitors (Moderate): May increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: Monitor therapyCYP3A4 Inhibitors (Strong): May enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Strong) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite oxymorphone may also be increased. Risk C: Monitor therapyDaridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modificationDesmopressin: Opioid Agonists may enhance the hyponatremic effect of Desmopressin.Risk C: Monitor therapyDexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine.Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modificationDifelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyDimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyDiuretics: Opioid Agonists may enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics.Risk C: Monitor therapyDroperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modificationEluxadoline: Opioid Agonists may enhance the constipating effect of Eluxadoline.Risk X: Avoid combinationFexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combinationFlunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine.Risk X: Avoid combinationFlunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam.Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modificationFusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combinationGastrointestinal Agents (Prokinetic): Opioid Agonists may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).Risk C: Monitor therapyHydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modificationKava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyKratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combinationLemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modificationLisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyLofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyMagnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyMethotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants.Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modificationMetoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyMetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE.Risk C: Monitor therapyMinocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyMonoamine Oxidase Inhibitors: OxyCODONE may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome.Risk X: Avoid combinationNalmefene: May diminish the therapeutic effect of Opioid Agonists. Management: Avoid the concomitant use of oral nalmefene and opioid agonists. Discontinue oral nalmefene 1 week prior to any anticipated use of opioid agonists. If combined, larger doses of opioid agonists will likely be required. Risk D: Consider therapy modificationNaltrexone: May diminish the therapeutic effect of Opioid Agonists. Management: Seek therapeutic alternatives to opioids.See full drug interaction monograph for detailed recommendations. Risk X: Avoid combinationNefazodone: Opioid Agonists (metabolized by CYP3A4) may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Opioid Agonists (metabolized by CYP3A4).Management: If concomitant use of opioid agonists that are metabolized by CYP3A4 and nefazodone is necessary, consider dose reduction of the opioid until stable drug effects are achieved. Monitor for increased opioid effects and serotonin syndrome/serotonin toxicity. Risk D: Consider therapy modificationOlopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combinationOpioids (Mixed Agonist / Antagonist): May diminish the analgesic effect of Opioid Agonists. Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Risk X: Avoid combinationOrphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine.Risk X: Avoid combinationOxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combinationParaldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde.Risk X: Avoid combinationPegvisomant: Opioid Agonists may diminish the therapeutic effect of Pegvisomant.Risk C: Monitor therapyPHENobarbital: May enhance the CNS depressant effect of OxyCODONE. PHENobarbital may decrease the serum concentration of OxyCODONE. Management: Avoid use of oxycodone and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined. Risk D: Consider therapy modificationPiribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil.Risk C: Monitor therapyPramipexole: CNS Depressants may enhance the sedative effect of Pramipexole.Risk C: Monitor therapyPrimidone: May enhance the CNS depressant effect of OxyCODONE. Primidone may decrease the serum concentration of OxyCODONE. Management: Avoid use of oxycodone and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a strong CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined. Risk D: Consider therapy modificationProcarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyRamosetron: Opioid Agonists may enhance the constipating effect of Ramosetron.Risk C: Monitor therapyRopeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased.Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modificationROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole.Risk C: Monitor therapyRotigotine: CNS Depressants may enhance the sedative effect of Rotigotine.Risk C: Monitor therapyRufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapySamidorphan: May diminish the therapeutic effect of Opioid Agonists. Risk X: Avoid combinationSerotonergic Agents (High Risk): Opioid Agonists (metabolized by CYP3A4) may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome.Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapySincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide.Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modificationSomatostatin Analogs: Opioid Agonists may diminish the analgesic effect of Somatostatin Analogs. Opioid Agonists may enhance the analgesic effect of Somatostatin Analogs.Risk C: Monitor therapySuccinylcholine: May enhance the bradycardic effect of Opioid Agonists. Risk C: Monitor therapySuvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant.Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary.Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modificationThalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide.Risk X: Avoid combinationValerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyZolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem.Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg formen who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modificationReproductive ConsiderationsLong-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction or infertility (Brennan 2013).Pregnancy ConsiderationsOxycodone crosses the placenta (Kokki 2012).According to some studies, maternal use of opioids may be associated with birth defects (including neural tube defects, congenital heart defects, and gastroschisis), poor fetal growth, stillbirth, and preterm delivery (CDC [Dowell 2016]).[US Boxed Warning]: Prolonged use of oxycodone during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. If chronic opioid exposure occurs in pregnancy, adverse events in the newborn (including withdrawal) may occur (Chou 2009). Symptoms of neonatal abstinence syndrome (NAS) following opioid exposure may be autonomic (eg, fever, temperature instability), gastrointestinal (eg, diarrhea, vomiting, poor feeding/weight gain), or neurologic (eg, high-pitched crying, hyperactivity, increased muscle tone, increased wakefulness/abnormal sleep pattern, irritability, sneezing, seizure, tremor, yawning) (Dow 2012; Hudak 2012). Mothers who are physically dependent on opioids may give birth to infants who are also physically dependent. Opioids may cause respiratory depression and psycho-physiologic effects in the neonate; newborns of mothers receiving opioids during labor should be monitored.Oxycodone is not commonly used to treat pain during labor and immediately postpartum (ACOG 209 2019) or chronic noncancer pain in pregnant women or those who may become pregnant (CDC [Dowell 2016]; Chou 2009).Breastfeeding ConsiderationsOxycodone is present in breast milk in variable concentrations.In one study, oxycodone was measurable in breast milk up to 37 hours after the last maternal dose and therapeutic concentrations were detected in the serum of a breastfeeding infant (Seaton 2007). Oxycodone was also detected in the urine of a breastfed infant (Sulton-Villavasso 2012).CNS depression, constipation, decreased feeding, and respiratory distress/irregular breathing have been observed in infants exposed to oxycodone via breast milk (Lam 2012; Sulton-Villavasso 2012). Withdrawal symptoms may occur when maternal use is discontinued or breastfeeding is stopped.Nonopioid analgesics are preferred for breastfeeding females who require pain control peripartum or for surgery outside of the postpartum period (ABM [Martin 2018]; ABM [Reece-Stremtan 2017]). When an opiate is needed, use of oxycodone in breastfeeding women is not recommended by some guidelines (Sachs 2013). Other guidelines note prolonged and frequent use may cause neonatal sedation (ABM [Martin 2018]). Maternal doses greater than 30 mg/day are not recommended (ABM [Martin 2018]; ACOG 209 2019).When opioids are needed in breastfeeding women, the lowest effective dose for the shortest duration of time should be used to limit adverse events in the mother and breastfeeding infant. In general, a single occasional dose of an opioid analgesic may be compatible with breastfeeding (WHO 2002). Breastfeeding women using opioids for postpartum pain or for the treatment of chronic maternal pain should monitor their infants for drowsiness, sedation, feeding difficulties, or limpness (ACOG 209 2019).Dietary ConsiderationsInstruct patient to avoid high-fat meals when taking some products (food has no effect on the reformulated OxyContin).Monitoring ParametersPain relief, respiratory and mental status, blood pressure; bowel function; signs/symptoms of misuse, abuse, and addiction; signs or symptoms of hypogonadism or hypoadrenalism (Brennan 2013)Alternate recommendations: Chronic pain (long-term therapy outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-based opioid use disorder treatment): Evaluate benefits/risks of opioid therapy within 1 to 4 weeks of treatment initiation and with dose increases. Re-evaluate benefits/risks every 3 months during therapy or more frequently in patients at increased risk of overdose or opioid use disorder. Urine drug testing is recommended prior to initiation and re-checking should be considered at least yearly (includes controlled prescription medications and illicit drugs of abuse). State prescription drug monitoring program (PDMP) data should be reviewed by clinicians prior to initiation and periodically during therapy (frequency ranging from every prescription to every 3 months) (Dowell [CDC 2016]).Mechanism of ActionBinds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depressionPharmaco*kineticsOnset of action: Pain relief: Immediate release: 10 to 15 minutes.Peak effect: Immediate release: 0.5 to 1 hour.Duration: Immediate release: 3 to 6 hours; Extended release: ≤12 hours.Distribution: Vd: Children 2 to 10 years: 2.1 L/kg (range: 1.2 to 3.7 L/kg); Adults: 2.6 L/kg; distributed to skeletal muscle, liver, intestinal tract, lungs, spleen, and brain.Protein binding: 38% to 45%.Metabolism: Hepatically via CYP3A4 to noroxycodone (has weak analgesic activity), noroxymorphone, and alpha- and beta-noroxycodol. CYP2D6 mediated metabolism produces oxymorphone (has analgesic activity; low plasma concentrations [<15%]), alpha- and beta-oxymorphol.Bioavailability: Extended release tablet, immediate release: 60% to 87%; Extended release capsule is not bioequivalent to extended release tablet; however AUC, is similar in a fed state.Half-life:Apparent: Immediate release: 3.2 to ~4 hours; Extended release tablet: 4.5 hours; Extended release capsule: 5.6 hours.Elimination: Children 2 to 10 years: 1.8 hours (range: 1.2 to 3 hours); Adults: 3.7 hours.Adults with CrCl <60 mL/minute: Half-life increases by 1 hour, but peak oxycodone concentrations increase by 50% and AUC increases by 60%.Adults with mild to moderate hepatic impairment: Half-life increases by 2.3 hours, peak oxycodone concentrations increase by 50%, and AUC increases by 95%.Time to peak, plasma: Immediate release: 1.2 to 1.9 hours; Extended release: 4 to 5 hours.Excretion: Urine: (~10% as parent; ~65% as metabolites [noroxycodone (23%, active), oxymorphone (10%, active), noroxymorphone (14%, weakly active), reduced metabolites (≤18%)]) (Kinnunen 2019).Pharmaco*kinetics: Additional ConsiderationsAltered kidney function: Higher peak plasma oxycodone (50%), and noroxycodone (20%), higher AUC for oxycodone (60%), noroxycodone (50%), and oxymorphone (40%) in patients with CrCl <60 mL/minute. There is an increased half-life elimination for oxycodone elimination of only 1 hour.Hepatic function impairment: Peak plasma oxycodone and noroxycodone concentrations 50% and 20% higher; AUC values are 95% and 65% higher, respectively, in mild to moderate hepatic impairment. Oxymorphone peak plasma concentration and AUC values are lower by 30% and 40%. The half-life elimination for oxycodone is increased by 2.3 hours.Pricing: USCapsule ER 12 Hour Abuse-Deterrent (Xtampza ER Oral)9 mg (per each): $7.1013.5 mg (per each): $10.4518 mg (per each): $13.2527 mg (per each): $18.4336 mg (per each): $22.69Capsules (oxyCODONE HCl Oral)5 mg (per each): $1.84 - $1.85Concentrate (oxyCODONE HCl Oral)100 mg/5 mL (per mL): $4.17 - $12.33Solution (oxyCODONE HCl Oral)5 mg/5 mL (per mL): $1.05 - $1.73Tablet Abuse-Deterrent (RoxyBond Oral)5 mg (per each): $13.1215 mg (per each): $15.8830 mg (per each): $21.40Tablet ER 12 Hour Abuse-Deterrent (oxyCODONE HCl ER Oral)10 mg (per each): $3.02 - $5.0320 mg (per each): $5.64 - $9.3740 mg (per each): $8.36 - $16.0580 mg (per each): $15.73 - $28.01Tablet ER 12 Hour Abuse-Deterrent (OxyCONTIN Oral)10 mg (per each): $5.7415 mg (per each): $8.4420 mg (per each): $10.6930 mg (per each): $14.8840 mg (per each): $18.3160 mg (per each): $25.9380 mg (per each): $31.96Tablets (Oxaydo Oral)5 mg (per each): $11.707.5 mg (per each): $17.53Tablets (oxyCODONE HCl Oral)5 mg (per each): $0.08 - $0.6210 mg (per each): $0.15 - $1.4515 mg (per each): $0.12 - $2.3720 mg (per each): $0.27 - $2.3230 mg (per each): $0.18 - $4.49Tablets (Roxicodone Oral)15 mg (per each): $6.2330 mg (per each): $12.23Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalAbtard (GB);Alnagon (RO);Dancex (IE);Endone (AU);Epethinan (IE);Ircodon (KR);Lynlor (GB);M-Oxy (PE);Orionox (FI, NO);Oxinovag (AR);Oxycod (IL);OxyContin (AR, AT, BR, CH, CL, CO, CR, CY, CZ, DK, DO, EC, EE, ES, FI, GB, GT, HK, HN, IE, IL, IT, MY, NI, NL, NO, NZ, PA, PE, PH, PL, PT, SE, SG, SV, VE);Oxycontin (BB, BH, CN, HR, HU, IS, LB, LU, RO, SI, SK, TR, TW, VN, ZA);Oxycontin CR (KR);Oxycontin LP (FR);Oxycontin Neo (PH);Oxyduo (PL);Oxyfast (JP);Oxygesic (DE);Oxyneo (ID, VN);Oxynorm (AT, AU, BE, CH, CY, DK, EG, ES, FI, FR, GB, HK, ID, IE, IS, MY, NO, NZ, PH, SE, SG, TR, TW, ZA);OxyNorm (JP);Oxynorm IV (SG);Plexicodim (MX);Proladone (AU);Reltebon (GB, HU);Targin (DE, IL)For country code abbreviations (show table)Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319. [PubMed 11487763]American College of Obstetricians and Gynecologists (ACOG). ACOG practice bulletin no. 209: obstetric analgesia and anesthesia. Obstet Gynecol. 2019;133(3):e208-e225. [PubMed 30801474]American Pain Society (APS). Pain assessment and management initiative (PAMI) dosing guide. Updated November 2016b.American Pain Society (APS). Principles of analgesic use. Seventh edition. 2016a.Anderson DT, Fritz KL, Muto JJ. Oxycontin: the concept of a "ghost pill" and the postmortem tissue distribution of oxycodone in 36 cases. J Anal Toxicol. 2002;26(7):448-459. [PubMed 12422999]APO-Oxycodone CR (oxycodone) [product monograph]. Toronto, Ontario, Canada: Apotex Inc; December 2021.Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007.Association of Paediatric Anaesthetists of Great Britain and Ireland (APA). Good practice in postoperative and procedural pain management, 2nd edition. Paediatr Anaesth. 2012;22(Suppl 1):1-79.Azhar A, Kim YJ, Haider A, et al. Response to oral immediate-release opioids for breakthrough pain in patients with advanced cancer with adequately controlled background pain. Oncologist. 2019;24(1):125-131. doi:10.1634/theoncologist.2017-0583 [PubMed 30254187]Based on expert opinion.Berde CB, Sethna NF. Analgesics for the treatment of pain in children. N Engl J Med. 2002;347(14):1094-1103. [PubMed 12362012]Berna C, Kulich RJ, Rathmell JP. Tapering long-term opioid therapy in chronic noncancer pain: evidence and recommendations for everyday practice. Mayo Clin Proc. 2015;90(6):828-842. doi:10.1016/j.mayocp.2015.04.003 [PubMed 26046416]Brennan MJ. The effect of opioid therapy on endocrine function. Am J Med. 2013;126(3)(suppl 1):S12-S18. doi:10.1016/j.amjmed.2012.12.001 [PubMed 23414717]Carr D. Management of acute pain in the patient chronically using opioids for non-cancer pain. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 11, 2021.Carvalho B, Sutton CD. Post-cesarean delivery analgesia. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 5, 2021.Centers for Disease Control and Prevention (CDC). Common elements in guidelines for prescribing opioids for chronic pain. https://www.cdc.gov/drugoverdose/pdf/common_elements_in_guidelines_for_prescribing_opioids-a.pdf. Published 2015. Accessed September 13, 2018.Centers for Disease Control and Prevention (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm [PubMed 6810084]Cheung CW, Ching Wong SS, Qiu Q, Wang X. Oral oxycodone for acute postoperative pain: a review of clinical trials. Pain Physician. 2017;20(2S):SE33-SE52. [PubMed 28226340]Chou R, Fanciullo GJ, Fine PG, et al, "Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain," J Pain, 2009, 10(2):113-30. [PubMed 19187889]Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016;17(2):131-157. doi:10.1016/j.jpain.2015.12.008 [PubMed 26827847]Coté CJ, Lerman J, Anderson B, eds. A Practice of Anesthesia for Infants and Children. 6th ed. Elsevier; 2019.Davison SN. Clinical pharmacology considerations in pain management in patients with advanced kidney failure. Clin J Am Soc Nephrol. 2019;14(6):917-931. doi:10.2215/CJN.05180418 [PubMed 30833302]Debono M, Chan S, Rolfe C, Jones TH. Tramadol-induced adrenal insufficiency. Eur J Clin Pharmacol. 2011; 67:865-867. doi:10.1007/s00228-011-0992-9 [PubMed 21243342]Dow K, Ordean A, Murphy-Oikonen J, et al, "Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario," J Popul Ther Clin Pharmacol, 2012, 19(3):e488-506. [PubMed 23241498]Dowell D. CDC guideline for prescribing opioids for chronic pain clarification [written communication]. Atlanta, GA: Centers for Disease Control and Prevention; February 28, 2019.Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016. MMWR Recomm Rep. 2016;65(1):1-49. doi:10.15585/mmwr.rr6501e1 [PubMed 26987082]Foral PA, Ineck JR, Nystrom KK. Oxycodone accumulation in a hemodialysis patient. South Med J. 2007;100(2):212-214. doi:10.1097/01.smj.0000242876.45747.0a [PubMed 17330696]Gallagher RM, Welz-Bosna M, Gammaitoni A. Assessment of dosing frequency of sustained-release opioid preparations in patients with chronic nonmalignant pain. Pain Med. 2007;8(1):71-74. [PubMed 17244106]Hill MV, Stucke RS, McMahon ML, Beeman JL, Barth RJ Jr. An educational intervention decreases opioid prescribing after general surgical operations. Ann Surg. 2018;267(3):468-472. doi:10.1097/SLA.0000000000002198 [PubMed 28267689]Hudak ML, Tan RC, Committee on Drugs, et al, "Neonatal Drug Withdrawal," Pediatrics, 2012, 129(2):e540-60. [PubMed 22291123]"Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics (AAP) Committee on Drugs. Pediatrics. 1997;99(2):268-278. [PubMed 9024461]Kinnunen M, Piirainen P, Kokki H, Lammi P, Kokki M. Updated clinical pharmaco*kinetics and pharmacodynamics of oxycodone. Clin Pharmaco*kinet. 2019;58(6):705-725. doi:10.1007/s40262-018-00731-3 [PubMed 30652261]Kirvela M, Lindgren L, Seppala T, Olkkola KT. The pharmaco*kinetics of oxycodone in uremic patients undergoing renal transplantation. J Clin Anesth. 1996;8(1):13-18. doi:10.1016/0952-8180(95)00092-5 [PubMed 8695073]Kokki M, Franco MG, Raatikainen K, et al. Intravenous oxycodone for pain relief in the first stage of labour--maternal pharmaco*kinetics and neonatal exposure. Basic Clin Pharmacol Toxicol. 2012;111(3):182-188. [PubMed 22448718]Koncicki HM, Unruh M, Schell JO. Pain management in CKD: a guide for nephrology providers. Am J Kidney Dis. 2017;69(3):451-460. doi:10.1053/j.ajkd.2016.08.039 [PubMed 27881247]Lam J, Kelly L, Ciszkowski C, et al. Central nervous system depression of neonates breastfed by mothers receiving oxycodone for postpartum analgesia. J Pediatr. 2012;160(1):33-37. [PubMed 21880331]Leuppi-Taegtmeyer A, Duthaler U, Hammann F, et al. Pharmaco*kinetics of oxycodone/naloxone and its metabolites in patients with end-stage renal disease during and between haemodialysis sessions. Nephrol Dial Transplant. 2019;34(4):692-702. doi:10.1093/ndt/gfy285 [PubMed 30189012]Marcus DA, Glick RM. Sustained-release oxycodone dosing survey of chronic pain patients. Clin J Pain. 2004;20(5):363-366. [PubMed 15322444]Mariano ER. Management of acute perioperative pain. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 12, 2021.Martin E, Vickers B, Landau R, Reece-Stremtan S. ABM clinical protocol #28, peripartum analgesia and anesthesia for the breastfeeding mother. Breastfeed Med. 2018;13(3):164-171. [PubMed 29595994]Nicholson B, Ross E, Sasaki J, Weil A. Randomized trial comparing polymer-coated extended-release morphine sulfate to controlled-release oxycodone HCl in moderate to severe nonmalignant pain. Curr Med Res Opin. 2006;22(8):1503-1514. [PubMed 16870075]Oxaydo (oxycodone) [prescribing information]. Wayne, PA: Zyla Life Sciences US Inc; March 2021.OxyContin (oxycodone) extended-release tablets [prescribing information]. Stamford, CT: Purdue Pharma LP; October 2021.Oxycodone hydrochloride capsules [prescribing information]. Allentown, PA: Genus Lifesciences Inc; July 2021.Oxycodone hydrochloride 1 mg/mL oral solution [prescribing information]. Allentown, PA: Genus Lifesciences Inc; July 2021.Oxycodone hydrochloride oral solution [prescribing information]. Berkeley Heights, NJ: Hikma Pharmaceuticals USA Inc; July 2021.Oxycodone hydrochloride oral solution [prescribing information]. Largo, FL: VistaPharm; March 2021.Oxycodone hydrochloride tablet [prescribing information]. Coventry, RI: Rhodes Pharmaceuticals LP; March 2021.Oxy IR (oxycodone) [product monograph]. Pickering, Ontario, Canada: Purdue Pharma; August 2020.Oxyneo (oxycodone) controlled release tablets [product monograph]. Toronto, Ontario, Canada: Purdue Pharma; July 2022.Paice JA, Ferrell B. The management of cancer pain. CA Cancer J Clin. 2011;61(3):157-182. doi:10.3322/caac.20112 [PubMed 21543825]Pain Assessment and Management Initiative. Pain management & dosing guide. https://pami.emergency.med.jax.ufl.edu/wordpress/files/2020/09/PAMI-Dosing-Guide-Nov.2.2020.pdf. Updated November 2020. Accessed October 12, 2021.Pino CA, Wakerman SE. Prescription of opioids for acute pain in opioid naïve patients. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 25, 2022.Portenoy RK, Mehta Z, Ahmed E. Cancer pain management with opioids: optimizing analgesia. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 12, 2021.Rakoski M, Goyal P, Spencer-Safier M, Weissman J, Mohr G, Volk M. Pain management in patients with cirrhosis. Clin Liver Dis (Hoboken). 2018;11(6):135-140. doi:10.1002/cld.711 [PubMed 30992804]Reece-Stremtan S, Campos M, Kokajko L; Academy of Breastfeeding Medicine. ABM clinical protocol #15: analgesia and anesthesia for the breastfeeding other, revised 2017. Breastfeed Med. 2017;12(9):500-506. [PubMed 29624435]Refer to manufacturer's labeling.Rosenquist R. Use of opioids in the management of chronic non-cancer pain. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 31, 2022.Roxicodone (oxycodone) [prescribing information]. Webster Groves, MO: SpecGx LLC; August 2022.Roxybond (oxycodone) [prescribing information]. Princeton, NJ: Protega Pharmaceuticals LLC; February 2022.Sachs HC, Committee On Drugs. The transfer of drugs and therapeutics into human breast milk: an update on selected topics. Pediatrics. 2013;132(3):e796-809. [PubMed 23979084]Seaton S, Reeves M, McLean S. Oxycodone as a component of multimodal analgesia for lactating mothers after Caesarean section: relationships between maternal plasma, breast milk and neonatal plasma levels. Aust N Z J Obstet Gynaecol. 2007;47(3):181-185. [PubMed 17550483]Sevarino KA. Medically supervised opioid withdrawal during treatment for addiction. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 12, 2021.Sulton-Villavasso C, Austin CA, Patra KP, et al. Index of suspicion. Case 1: Infant who has respiratory distress. Case 2: Abnormal behavior, seizures, and altered sensorium in a 7-year-old boy. Case 3: Fever and dysphagia in a 4-year-old girl. Pediatr Rev. 2012;33(6):279-284. [PubMed 22659261]Supeudol (oxycodone) [product monograph]. Boucherville, Quebec, Canada: Sandoz Canada Inc; September 2019.Tawfic QA, Bellingham G. Postoperative pain management in patients with chronic kidney disease. J Anaesthesiol Clin Pharmacol. 2015;31(1):6-13. doi:10.4103/0970-9185.150518 [PubMed 25788766]Tran BW, Kohan LR, Vorenkamp KE. Postoperative oxycodone toxicity in a patient with chronic pain and end-stage renal disease. A A Case Rep. 2015;4(4):44-46. doi:10.1213/XAA.0000000000000115 [PubMed 25689360]US Department of Health and Human Services (HHS). HHS guide for clinicians on the appropriate dosage reduction or discontinuation of long-term opioid analgesics. https://www.hhs.gov/opioids/sites/default/files/2019-10/Dosage_Reduction_Discontinuation.pdf. Updated October 2019. Accessed October 12, 2021.Weinberg DS, Inturrisi CE, Reidenberg B, et al. Sublingual absorption of selected opioid analgesics. Clin Pharmacol Ther. 1988;44(3):335-342. doi:10.1038/clpt.1988.159 [PubMed 2458208]World Health Organization (WHO). Breastfeeding and maternal medication, recommendations for drugs in the eleventh WHO model list of essential drugs. 2002. Available at http://www.who.int/maternal_child_adolescent/documents/55732/en/Xtampza ER (oxycodone) [prescribing information]. Cincinnati, OH: Patheon Pharmaceuticals; March 2021.Topic 9729 Version 656.0

CloseOxycodone: Pediatric drug informationOxycodone: Pediatric drug information(For additional information see "Oxycodone: Drug information" and see "Oxycodone: Patient drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)ALERT: US Boxed WarningAddiction, abuse, and misuse:Oxycodone exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing oxycodone and monitor all patients regularly for the development of these behaviors or conditions.Opioid analgesic risk evaluation and mitigation strategy (REMS)To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the FDA has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to health care providers. Health care providers are strongly encouraged to complete a REMS-compliant education program and counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products; emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and consider other tools to improve patient, household, and community safety.Life-threatening respiratory depression:Serious, life-threatening, or fatal respiratory depression may occur with use of oxycodone. Monitor for respiratory depression, especially during initiation of oxycodone or following a dose increase. Instruct patients to swallow oxycodone tablets whole; crushing, chewing, or dissolving oxycodone ER tablets can cause rapid release and absorption of a potentially fatal dose of oxycodone.Accidental ingestion:Accidental ingestion of even one dose of oxycodone, especially by children, can result in a fatal overdose of oxycodone.Neonatal opioid withdrawal:Prolonged use of oxycodone during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.Cytochrome P450 3A4 interaction:The concomitant use of oxycodone with all cytochrome P450 (CYP-450) 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used CYP3A4 inducer may result in an increase in oxycodone plasma concentration. Monitor patients receiving oxycodone and any CYP3A4 inhibitor or inducer.Risks from concomitant use with benzodiazepines or other CNS depressants:Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of oxycodone and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.Risk of medication errors (oral solution):Ensure accuracy when prescribing, dispensing, and administering oxycodone oral solution. Dosing errors due to confusion between mg and mL, and other oxycodone oral solutions of different concentrations can result in accidental overdose.Brand Names: USOxaydo;OxyCONTIN;Roxicodone;RoxyBond;Xtampza ERBrand Names: CanadaACT Oxycodone CR [DSC];APO-Oxycodone CR;Oxy-IR;OxyNEO;PMS-OxyCODONE;PMS-OxyCODONE CR;Supeudol;Supeudol 10;Supeudol 20Therapeutic CategoryAnalgesic, OpioidDosing: PediatricNote: Doses should be titrated to appropriate effect. Multiple concentrations of oral solution available (20 mg/mL and 1 mg/mL); the highly concentrated formulation (20 mg/mL) should only be used in opioid-tolerant patients (taking ≥30 mg/day of oxycodone or equivalent for ≥1 week). Orders for oxycodone oral solutions (20 mg/mL or 1 mg/mL) should be clearly written to include the intended dose (in mg not mL) and the intended product concentration to be dispensed to avoid potential dosing errors:Analgesia, moderate to severe painAnalgesia, moderate to severe pain: Limited data available:Infants ≤6 months: Immediate release: Oral solution (1 mg/mL): Oral: Initial dose: 0.025 to 0.05 mg/kg/dose every 4 to 6 hours as needed (Ref).Infants >6 months, Children, and Adolescents:Patient weight <50 kg: Immediate release: Oral: Initial dose: 0.1 to 0.2 mg/kg/dose every 4 to 6 hours as needed; for severe pain some experts have recommended an initial dose of 0.2 mg/kg; usual maximum dose range: 5 to 10 mg/dose (Ref).Patient weight ≥50 kg: Immediate release: Oral: Initial dose: 5 to 10 mg every 4 to 6 hours as needed; for severe pain an initial dose of 10 mg may be used; usual maximum dose: 20 mg/dose (Ref).Analgesia, severe pain requiring around-the-clock long-term opioid therapyAnalgesia, severe pain requiring around-the-clock long-term opioid therapy: Note: Use only in pediatric patients ≥11 years of age who are already receiving opioid therapy for ≥5 consecutive days, tolerating a minimum daily opioid dose of ≥20 mg of oxycodone orally or its equivalent at least for the 2 days immediately prior to starting extended-release oxycodone tablets, and for which alternative treatment options are inadequate. Prior to initiation, all other around-the-clock opioid therapy must be discontinued.Children ≥11 years and Adolescents: Extended-release tablets (eg, OxyContin): Oral:Initial dose: Based on current opioid regimen dose; use the following conversion factor table and equation to convert the current opioid(s) daily dose to the extended-release oxycodone tablet daily dose.Note: Substantial interpatient variability exists due to patient specific factors, relative potency of different opioids, and dosage forms; therefore, it is preferable to underestimate the initial 24-hour oral oxycodone requirements and utilize rescue medication (immediate-release opioid):Initial dose of extended-release oxycodone tablets every 12 hours = (mg/day of current opioid regimen X conversion factor)/2Dose calculations or adjustments for specific clinical scenarios:• If rounding is necessary, numerical value should be rounded down to the nearest tablet strength. If calculated daily dose is <20 mg, do not start extended-release oxycodone tablet as there is no safe tablet strength available.• If more than one opioid in the regimen, calculate the approximate extended-release oxycodone tablet dose for each opioid and sum the totals for the approximate total daily extended-release oxycodone tablet dose, then divide by 2 for the 12-hour extended-release oxycodone dose.• If current opioid regimen includes a fixed-dose opioid/nonopioid dosage form (eg, hydrocodone/acetaminophen), only the mg of opioid should be used in the conversion calculations.• If patient receiving concomitant CNS depressants, reduce extended-release oxycodone tablet starting dose by 1/3 to 1/2 the calculated initial dose.• If asymmetric dosing, the higher dose should be scheduled as the morning dose, and the lower dose 12 hours later.Note: The following conversion table should ONLY be used to convert opioid doses to extended-release oxycodone tablet (not from extended-release oxycodone tablet to other opioids; it is NOT a table of equianalgesic doses as it may overestimate initial dose).Conversion Factor for Calculating Initial Extended-Release Oxycodone Tablet Dose in Pediatric Patients ≥11 YearsCurrent opioid regimen to be converted to extended-release oxycodone tabletConversion factorOralParenteralaOxycodone1--Hydrocodone0.9--Hydromorphone420Morphine0.53Tramadol0.170.2a For patients receiving high-dose parenteral opioids, a more conservative conversion factor should be applied (ie, lower numerical conversion factor); for example, for high-dose parenteral morphine, a conversion of 1.5 should be used for calculations instead of 3.Conversion from fentanyl patch to extended-release oxycodone tablet: Limited data available: Children ≥11 years and Adolescents: Note: Remove fentanyl patch ≥18 hours prior to starting extended-release oxycodone. Initial dose based on current opioid regimen dose; the manufacturer suggests using the conservative conversion factor of 10 mg every 12 hours of extended-release oxycodone tablet for each 25 mcg/hour fentanyl transdermal patch; systemic assessment of this suggested conversion has not been completed, monitor patients closely.Maintenance dose: Dosage adjustment (titration): After initiation of extended-release oxycodone tablet, adjust dose in small increments (up to 25% of current total daily dosage) no more frequently than every 1 to 2 days until desired pain control; patients may require rescue doses of an immediate-release analgesic during dose titration. Observe for signs and symptoms of opioid withdrawal or signs of oversedation/toxicity; if unacceptable adverse reactions occur, the subsequent dose may be reduced.Discontinuation of therapy: When discontinuing chronic opioid therapy, the dose should be gradually tapered down. An optimal universal tapering schedule for all patients has not been established (Ref). Specific pediatric protocols are lacking; based on experience in adults, proposed schedules range from slow (eg, 10% reductions per week) to rapid (eg, 25% to 50% reduction every few days) (Ref). Tapering schedules should be individualized to minimize opioid withdrawal while considering patient-specific goals and concerns as well as the pharmaco*kinetics of the opioid being tapered. An even slower taper may be appropriate in patients who have been receiving opioids for a long duration (eg, years), particularly in the final stage of tapering, whereas more rapid tapers may be appropriate in patients experiencing severe adverse events (Ref). Monitor carefully for signs/symptoms of withdrawal. If the patient displays withdrawal symptoms, consider slowing the taper schedule; alterations may include increasing the interval between dose reductions, decreasing amount of daily dose reduction, or pausing the taper and restarting when the patient is ready (Ref). Continue to offer nonopioid analgesics as needed for pain management during the taper; consider nonopioid adjunctive treatments for withdrawal symptoms.Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricIn general, oxycodone clearance may be decreased in patients with renal impairment; initiate therapy at low end of dosing range.Immediate release: Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, the following adjustments have been recommended (Ref):GFR ≥50 mL/minute/1.73 m2: No dosage adjustment required.GFR 10 to 50 mL/minute/1.73 m2: Administer 75% of dose.GFR <10 mL/minute/1.73 m2: Administer 50% of dose.Hemodialysis: Administer 50% of dose posthemodialysis.Peritoneal dialysis: Administer 50% of dose.Extended-release tablets (eg, OxyContin): Children ≥11 years and Adolescents: CrCl <60 mL/minute: Serum concentrations are increased ~50%. Initiate at the low end of the dosage range (use caution); adjust dose as clinically indicated. Doses of 33% to 50% of usual initial dosing have been recommended; if the reduced dose is less than smallest available dosage form, consider alternative analgesic.Dosing: Hepatic Impairment: PediatricImmediate release: There are no dosage adjustments provided in the manufacturer's labeling; based on experience in adult patients, may consider a conservative approach of reduced initial doses; adjust dose based on clinical response.Extended-release tablets (eg, OxyContin): Children ≥11 years and Adolescents: Initial: One-third (1/3) to one-half (1/2) of the usual starting dose; carefully titrate dose to appropriate effect. If reduced dose is less than smallest available dosage form, consider alternative analgesic.Dosing: Adult(For additional information see "Oxycodone: Drug information")Note: Place in therapy: When used for managing moderate to severe pain, opioids may be part of a comprehensive, multimodal, patient-specific treatment plan for pain. Maximize nonopioid analgesia, if appropriate, prior to initiation of opioid analgesia (Ref). Dose selection: Dosing provided is based on typical doses and some patients may require higher or lower doses. Individualize dosing and dosing intervals based on patient-specific factors (eg, comorbidities, severity of pain, concomitant medications, cachexia, general condition, degree of opioid experience/tolerance) and titrate to patient-specific treatment goals (eg, improvement in function and quality of life, decrease in pain using a validated pain rating scale). Use the lowest effective dose for the shortest period of time. Safety: Consider prescribing naloxone for patients with factors associated with an increased risk for overdose, such as history of overdose or substance use disorder, higher opioid dosages (≥50 morphine milligram equivalents [MME]/day orally [equivalent to ≥33 mg oxycodone/day]), and/or concomitant benzodiazepine use (Ref).Acute pain in opioid-naive patientsAcute pain in opioid-naive patients: General dosing: Note: For acute non–cancer-related pain severe enough to require an opioid, utilize multimodal pain control, maximize nonopioid analgesics, and limit the quantity prescribed to the expected duration of acute pain; a quantity sufficient for ≤3 days is often adequate, whereas >7 days is rarely needed. Do not use long-acting preparations for treatment of acute pain (Ref).Immediate release: Oral: Initial: 5 mg every 4 to 6 hours as needed; adjust dose according to patient response. Usual dosage range: 5 to 15 mg every 4 to 6 hours as needed. If usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies. For outpatient use, usually up to 20 mg/day for moderate pain or up to 30 mg/day for severe pain will suffice. Dosing is based on severity of pain and patient-specific factors; reduced dosing may be indicated in patients with comorbidities (Ref).Rectal [Canadian product]: Usual dosage range: One (10 or 20 mg) suppository up to 3 to 4 times daily as needed. If usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies (Ref).Acute pain in patients on chronic opioid therapyAcute pain (eg, breakthrough cancer pain) in patients on chronic opioid therapy:Immediate release: Oral: Usual dose: In conjunction with the scheduled opioid, administer 5% to 15% (rarely up to 20%) of the 24-hour oxycodone requirement (or MME) as needed using an IR formulation every 4 to 6 hours with subsequent dosage adjustments based upon response (Ref). Note: If chronic opioid is not oxycodone, use MME calculations cautiously due to lack of complete cross-tolerance; generally, reduce calculated dose by 25% to 50%; conversions from methadone are highly variable and require extreme caution (Ref).Acute postoperative pain, postoperative recovery/postanesthesia care unitAcute postoperative pain, postoperative recovery/postanesthesia care unit:Note: Optimize multimodal perioperative pain management (eg, regional or local anesthesia, nerve blocks, nonopioid analgesics, other adjuvants) to minimize opioid use (Ref). Refer to institutional protocols.Opioid-naive patients: Immediate release: Oral: Usual dosage range: 5 to 10 mg every 4 to 6 hours as needed. If usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies. Dosing is based on severity of pain and patient-specific factors; reduced dosing may be indicated in patients with comorbidities (Ref).Chronic pain, including chronic cancer painChronic pain, including chronic cancer pain:Note: Before starting opioid therapy for chronic pain, establish realistic goals for pain and function, and consider how therapy will be discontinued if benefits do not outweigh risks (Ref). Opioids, including oxycodone, are not the preferred therapy for chronic noncancer pain due to insufficient evidence of benefit and risk of serious harm; nonpharmacologic treatment and nonopioid analgesics are preferred, with the exception of chronic pain from active cancer, sickle cell disease, and end-of-life care. Consider opioids, including oxycodone, only in patients who experience clinically meaningful improvement in pain and function that outweighs patient safety risks (Ref).Opioid-naive patients: In general, for noncancer pain, establish oxycodone requirement using IR formulations (Ref). In patients with cancer pain, may switch to a long-acting formulation earlier in the course of therapy (Ref).Noncancer or cancer pain: Immediate release:Oral: Initial: 2.5 to 10 mg every 4 to 6 hours as needed or scheduled around the clock (eg, cancer pain); adjust dose according to patient response (see "Titration" below). Usual maintenance dosage range: 5 to 15 mg every 4 to 6 hours as needed or scheduled around the clock. If usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies. Dosing is based on severity of pain and patient-specific factors; start at the lower end of dosing range (Ref).Titration: Noncancer pain: Adjust dose according to patient response; if needed, increase the dose slowly in increments of no more than 25% to 50% of the total daily dose (Ref). Note: To reduce risk of overdose in noncancer pain (excluding patients with sickle cell disease and palliative care), use caution when increasing opioid dosage to ≥50 MME/day (equivalent to ≥33 mg oxycodone/day) and avoid increasing dosage to ≥90 MME/day (equivalent to ≥60 mg oxycodone/day) (Ref).Cancer pain: Adjust dose according to patient response; if needed, increase the fixed scheduled dose by 30% to 100% of the total dose taken in the prior 24-hour period including total amount of rescue medication used; if pain score decreased and functional assessment improved, continue current effective dosing (Ref).Rectal [Canadian product]: Usual dosage range: One (10 or 20 mg) suppository up to 3 to 4 times daily as needed. If usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies (Ref).Opioid-tolerant patients (also refer to "Dose Conversions for Pain Management"):Extended release: Note: Dosage forms: Dose of ER capsules is expressed as oxycodone base and dose of ER tablets is expressed as oxycodone hydrochloride; 9 mg of oxycodone base is equivalent to 10 mg oxycodone hydrochloride. Oxycodone ER capsules and ER tablets are not bioequivalent; monitor for changes in efficacy or tolerability and adjust dose if needed. Place in therapy: Although manufacturer's labeling contains directions for initiating ER oxycodone products in patients who are opioid-naive with chronic pain, these preparations should not be used as initial therapy. Instead, initiate treatment with an IR preparation to more accurately determine the daily opioid requirement and decrease the risk of overdose. Unless pain is associated with cancer, palliative care, or sickle cell disease, the CDC recommends that ER opioids be reserved for patients who have received IR opioids daily for ≥1 week yet continue to experience severe, continuous pain (Ref).ER tablet (oxycodone hydrochloride): Oral: See "Dose Conversions for Pain Management." Calculated dose may be administered every 12 hours.ER capsule (oxycodone base): Oral: See "Dose Conversions for Pain Management." Calculated dose may be administered every 12 hours. Maximum dose: 288 mg/day; safety of excipients in higher daily doses has not been established.Titration: After initiation of oxycodone ER, adjust dose in increments of 25% to 50% no more frequently than every 1 to 2 days until desired pain control. Patients may require rescue doses of an IR analgesic during dose titration. Observe for signs and symptoms of opioid withdrawal or signs of oversedation/toxicity; if unacceptable adverse reactions occur, reduce the dose. To reduce risk of overdose in noncancer pain (excluding patients with sickle cell disease and palliative care), use caution when increasing opioid dosage to ≥50 MME/day (equivalent to ≥33 mg oxycodone/day) and avoid increasing dosage to ≥90 MME/day (equivalent to ≥60 mg oxycodone/day) (Ref). Note: Some clinicians have reported better efficacy with more frequent dosing (ie, every 8 hours) (Ref); however, dosing more frequently than every 12 hours is not recommended by the manufacturer and safety has not been established.Dose conversions for pain management: Note: Equianalgesic conversions serve only as a general guide to estimate opioid dose equivalents for patients on scheduled doses of opioids. Multiple factors must be considered for safely individualizing conversion of opioid analgesia. In general, for noncancer pain, the decision to convert from an IR to an ER formulation should be individualized and reserved for those with severe continuous pain who have been taking opioids for ≥1 week (Ref).Converting from IR oxycodone to ER oxycodone preparations: Total daily oral oxycodone dose may be administered in 2 divided doses. Note: Dose of ER capsules is expressed as oxycodone base and the dose of ER tablets and IR formulations is expressed as oxycodone hydrochloride; 9 mg of oxycodone base is equivalent to 10 mg oxycodone hydrochloride.Converting between ER oxycodone preparations: Dose of ER capsules is expressed as oxycodone base and the dose of ER tablets is expressed as oxycodone hydrochloride; 9 mg of oxycodone base is equivalent to 10 mg oxycodone hydrochloride. Oxycodone ER capsules and ER tablets are not bioequivalent; monitor for changes in efficacy or tolerability and adjust dose if needed. Converting to/from oxycodone to/from a different opioid (parenteral or oral): Refer to published equianalgesic opioid conversion data (or institutional protocols) for guidance. Conversion ratios are only approximations and substantial interpatient variability exists; therefore, it is safer to underestimate a patient’s daily oral requirement and provide breakthrough pain relief with IR formulations than to risk overestimating daily requirements. When switching to a new opioid (except to/from methadone), reduce initial daily calculated equianalgesic dose of the new opioid by 25% to 50% to adjust for lack of complete mu receptor cross-tolerance (conversions to/from methadone are highly variable and require extreme caution) (Ref).Converting from transdermal fentanyl to oxycodone ER: Remove fentanyl patch at least 18 hours prior to starting oxycodone ER. The manufacturer suggests a conservative conversion approach of substituting each fentanyl 25 mcg/hour transdermal patch with 9 mg every 12 hours (oxycodone ER capsule) or 10 mg every 12 hours (oxycodone ER tablets). Systematic assessment of this suggested conversion has not been completed; monitor patients closely.Converting from methadone to oxycodone ER: Extreme caution and close monitoring is required when converting methadone to another opioid. Ratio between methadone and other opioid agonists varies widely according to previous dose exposure. Methadone has a long half-life and can accumulate in the plasma.Discontinuation or tapering of therapy: When reducing the dose, discontinuing, or tapering long-term opioid therapy, the dose should be gradually tapered. An optimal tapering schedule has not been established (Ref). Proposed schedules range from slow (eg, 10% reduction per week or 10% reduction per month depending on duration of long-term therapy) to rapid (eg, 25% to 50% reduction every few days) (Ref). Individualize dosing based on discussions with patient to minimize withdrawal while considering patient-specific goals and concerns, as well as the opioid’s pharmaco*kinetics. Slower tapers may be appropriate after long-term use (eg, years), particularly in the final stage of tapering, whereas more rapid tapers may be appropriate in patients experiencing severe adverse effects (Ref). During tapering, patients may be at an increased risk of overdose if they return to their original (or higher) opioid dose or use illicit opioids, due to rapid loss of tolerance; consider prescribing naloxone (Ref). Monitor carefully for signs/symptoms of withdrawal. If the patient displays withdrawal symptoms, consider slowing the taper schedule; alterations may include increasing the interval between dose reductions, decreasing amount of daily dose reduction, pausing the taper and restarting when the patient is ready, and/or coadministration of an alpha-2 agonist (eg, clonidine) to blunt withdrawal symptoms (Ref). Continue to offer nonopioid analgesics as needed for pain management during the taper; consider nonopioid adjunctive treatments for withdrawal symptoms (eg, GI symptoms, muscle spasm) as needed (Ref).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultThe renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.Note: There are no specific dose adjustments provided in the manufacturer's labeling. Oxycodone is excreted as parent drug (~10%) and as active to weakly active metabolites (~47%) with varying degrees of analgesic activity (Ref); half-life is prolonged and accumulation of active metabolites occurs in patients with kidney impairment (Ref). Use of other opioids may be preferred for management of severe pain in patients with kidney impairment (Ref).Note: When making dose adjustments for the rectal formulation [Canadian product], do not break, crush, cut, or dissolve the suppositories.Altered kidney function:CrCl ≥60 mL/minute: No dosage adjustment necessary.CrCl 30 to <60 mL/minute:Immediate release: Oral, rectal [Canadian product]: Initial: Administer 50% to 75% of usual dose no more frequently than every 6 hours (Ref). Use with caution; titrate gradually based on patient response and adverse effects.Extended release: Oral: Initial: Administer 50% to 75% of usual dose every 12 to 24 hours; if the reduced dose is less than smallest available dosage form, consider alternative analgesic. Use with caution; titrate gradually based on patient response and adverse effects (Ref).CrCl <30 mL/minute:Immediate release: Oral, rectal [Canadian product]: Initial: Administer 50% of usual dose no more frequently than every 8 hours. Use with caution; titrate gradually based on patient response and adverse effects (Ref).Extended release: Oral: ER formulations should preferably be avoided in patients with severe impairment (Ref).Hemodialysis, intermittent (thrice weekly): Slightly dialyzable (10.6%) (Ref):Immediate release: Oral, rectal [Canadian product]: Initial: Administer 50% of usual dose no more frequently than every 8 hours; titrate gradually based on patient response and adverse effects (Ref). Use with caution; cases of oxycodone toxicity have been reported in hemodialysis patients (Ref).Extended release: Oral: ER formulations should preferably be avoided in patients with severe impairment (Ref).Peritoneal dialysis:Immediate release: Oral, rectal [Canadian product]: Initial: Administer 50% of usual dose no more frequently than every 8 hours; titrate gradually based on patient response and adverse effects (Ref); use with caution.Extended release: Oral: ER formulations should preferably be avoided in patients with severe impairment (Ref).CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Close monitoring of response (analgesia) and adverse reactions (eg, sedation, CNS and respiratory depression) due to drug accumulation is important.Immediate release: Oral, rectal [Canadian product]: Initial: Administer 50% of usual dose no more frequently than every 6 hours; titrate gradually based on patient response and adverse effects (Ref).Extended release: Oral: Avoid use.PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response (analgesia) and adverse reactions (eg, sedation, CNS and respiratory depression) due to drug accumulation is important.Immediate release: Oral, rectal [Canadian product]: Initial: Administer 50% of usual dose no more frequently than every 6 hours; titrate gradually based on patient response and adverse effects (Ref).Extended release: Oral: Avoid use.Dosing: Hepatic Impairment: AdultImmediate release: Initiate therapy at 33% to 50% the usual dosage and titrate carefully. For patients with severe impairment, consider extending the dosing interval based on response and tolerability (eg, every 6 to 12 hours) (Ref).Extended release tablets or Extended release capsules: Initial: Initiate oxycodone ER with 33% to 50% of the calculated recommended dose. If reduced dose is less than smallest available dosage form consider alternative analgesic.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.[DSC] = Discontinued productCapsule, Oral, as hydrochloride: Generic: 5 mgCapsule ER 12 Hour Abuse-Deterrent, Oral: Xtampza ER: 9 mg (100 ea); 13.5 mg (100 ea); 18 mg (100 ea); 27 mg (100 ea); 36 mg (100 ea)Concentrate, Oral, as hydrochloride: Generic: 100 mg/5 mL (30 mL)Solution, Oral, as hydrochloride: Generic: 5 mg/5 mL (5 mL, 15 mL, 473 mL, 500 mL)Tablet, Oral, as hydrochloride: Oxaydo: 5 mg, 7.5 mgRoxicodone: 5 mg [DSC] [scored]Roxicodone: 15 mg [scored; contains fd&c blue #2 (indigotine), quinoline yellow (d&c yellow #10)]Roxicodone: 30 mg [scored]Generic: 5 mg, 10 mg, 15 mg, 20 mg, 30 mgTablet Abuse-Deterrent, Oral: RoxyBond: 15 mg, 30 mg [contains fd&c blue #2 (indigotine)]Tablet Abuse-Deterrent, Oral, as hydrochloride: RoxyBond: 5 mgTablet ER 12 Hour Abuse-Deterrent, Oral, as hydrochloride: OxyCONTIN: 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mgOxyCONTIN: 80 mg [contains fd&c blue #2 (indigo carm) aluminum lake]Generic: 10 mg, 15 mg [DSC], 20 mg, 30 mg [DSC], 40 mg, 60 mg [DSC], 80 mgGeneric Equivalent Available: USMay be product dependentDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Suppository, Rectal: Supeudol 10: 10 mg (12 ea)Supeudol 20: 20 mg (12 ea)Tablet, Oral, as hydrochloride: Oxy-IR: 5 mg, 10 mg, 20 mgSupeudol: 5 mg, 10 mg, 20 mgGeneric: 5 mg, 10 mg, 20 mgTablet ER 12 Hour Abuse-Deterrent, Oral, as hydrochloride: OxyNEO: 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mgOxyNEO: 80 mg [contains fd&c blue #2 (indigo carm) aluminum lake]Tablet Extended Release 12 Hour, Oral: Generic: 5 mg, 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, 80 mgDosage Forms ConsiderationsXtampza ER: Strength is expressed in terms of oxycodone base.9 mg equivalent to 10 mg oxycodone hydrochloride13.5 mg equivalent to 15 mg oxycodone hydrochloride18 mg equivalent to 20 mg oxycodone hydrochloride27 mg equivalent to 30 mg oxycodone hydrochloride36 mg equivalent to 40 mg oxycodone hydrochlorideControlled SubstanceC-IIMedication Guide and/or Vaccine Information Statement (VIS)An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:Oxaydo: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202080s012lbl.pdf#page=30Oxycodone hydrochloride capsules: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/200534s011lbl.pdf#page=30Oxycodone hydrochloride oral solution: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/201194s009lbl.pdf#page=33OxyContin: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/022272s046lbl.pdf#page=48Roxybond: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/209777s007lbl.pdf#page=39Roxicodone: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021011s011lbl.pdf#page=30Xtampza ER: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208090s015lbl.pdf#page=39Administration: PediatricOral:Immediate release (capsule, oral solution, tablets): May administer with food to decrease GI upset:Oral solution: Available in 2 strengths: 1 mg/mL and a concentrated oral solution (20 mg/mL). Precautions should be taken to avoid confusion between the different concentrations; prescriptions should have the concentration specified as well as the dose clearly represented as milligram (mg) of oxycodone, not volume (mL). The enclosed calibrated oral syringe should always be used to administer the concentrated oral solution to ensure the dose is measured and administered accurately. The concentrated oral solution (20 mg/mL) should only be used in opioid-tolerant patients (taking ≥30 mg/day of oxycodone or equivalent for ≥1 week).Tablet (Oxaydo): Swallow whole with adequate water to ensure complete swallowing immediately after placing in the mouth; the formulation uses technology designed to discourage common methods of tampering to prevent misuse/abuse. The tablet should not be wet prior to placing in the mouth. Do not crush, chew, or dissolve nor administer via feeding tubes (eg, gastric, NG) due to potential for obstruction.Extended release: Tablet (eg, OxyContin): May administer with food to decrease GI upset. Swallow whole; do not moisten, dissolve, cut, crush, chew, or break as this would result in rapid release of oxycodone and absorption of a potentially fatal dose of drug. Administer one at a time and follow each with water immediately after placing in the mouth. For oral use only; do not administer rectally; increased risk of adverse events due to better rectal absorption.Administration: AdultAppropriate laxatives should be administered to avoid the constipating side effects associated with use. Antiemetics may be needed for persistent nausea. Some dosage forms (eg, ER) may not be appropriate for administration through feeding tubes (eg, gastric, NG). Refer to product labeling.ER dosage forms:Oral: Tablet: Administer with or without food. Swallow tablet whole. Do not moisten, dissolve, cut, crush, break, or chew extended release tablets. Extended release tablets should be administered one at a time and each followed with water immediately after placing in the mouth.Capsule: Administer each dose with food and approximately the same amount. For patients with difficulty swallowing, capsule may be opened and the contents sprinkled on soft foods (eg, applesauce, pudding, yogurt, ice cream, jam) or into a cup for administration directly into the mouth. Rinse mouth immediately afterwards to ensure all contents have been swallowed. Contents of capsule may also be administered through a nasogastric (NG) tube or gastrostomy tube (G-tube). Flush tube with water first, then pour capsule contents directly into tube (do not premix capsule contents with fluid that will be used to flush them through the tube). After contents have been placed in tube, flush tube with 15 mL of water, milk, or liquid nutritional supplement once and then repeat twice with 10 mL.Bariatric surgery: Tablet, abuse deterrent and extended or controlled release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Roxybond (oxycodone) tablets are formulated to have increased resistance to cutting, crushing, grinding, or breaking. Pharmaco*kinetics are similar to other IR oxycodone formulations. Nonabuse-deterrent IR tablet, capsule, and oral solution formulations are available. Oxycodone ER capsule contents may be taken by sprinkling the contents onto soft food (ie, applesauce, ice cream, yogurt). If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, clinicians should be advised that oral morphine has been shown to have significantly increased Cmax and decreased Tmax in the immediate (1 to 2 weeks) and long-term (6-months) period after bariatric surgery.IR dosage forms:Oral:Capsule: Administer with or without food.Oral solution: Administer with or without food. Available in two strengths; 1 mg/mL and a concentrated oral solution (20 mg/mL). Precautions should be taken to avoid confusion between the different concentrations; prescriptions should have the concentration specified as well as the dose clearly represented as milligram (mg) of oxycodone, not volume (mL). The enclosed calibrated oral syringe should always be used to administer the concentrated oral solution to ensure the dose is measured and administered accurately. The concentrated oral solution (20 mg/mL) may be used in opioid-tolerant patients (taking ≥30 mg/day of oxycodone or equivalent for ≥1 week); may also be used in palliative care patients who have difficulty and/or are unable to swallow. The concentrate is not substantially absorbed sublingually/orally and requires the GI tract for effective absorption (Ref).Tablets:Without abuse deterrent: Administer with or without food. When administered with food, onset may be delayed.With abuse deterrent:Oxaydo: Administer with or without food. Do not crush, chew, or dissolve the tablets. Due to inactive ingredient that causes nasal burning (upon snorting) and throat irritation, the tablet must be swallowed whole with enough water to ensure complete swallowing immediately after placing in the mouth. The tablet should not be wet prior to placing in the mouth.Rectal:Suppository [Canadian product]: Administer rectally. Do not break, crush, cut, or dissolve the suppositories.Storage/StabilityStore at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Protect from light and moisture.Suppository [Canadian product]: Store below 25°C (77°F).UseImmediate-release formulations (capsules, oral solution, and tablets [eg, Oxaydo, RoxyBond, Roxicodone]): Management of acute or chronic moderate to severe pain for which the use of an opioid analgesic is appropriate and alternative treatments are inadequate (FDA approved in adults).Extended-release capsule (Xtampza ER): Management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate (FDA approved in adults).Extended-release tablets (eg, OxyContin): Management of pain severe enough to require daily, around-the-clock, long-term opioid therapy for which alternative treatment options are inadequate in adults and also opioid-tolerant in pediatric patients (FDA approved in pediatric patients ≥11 years receiving and tolerating ≥20 mg/day oxycodone or its equivalent and adults).Limitations of use: Reserve oxycodone for use in patients for whom alternative treatment options (eg, nonopioid analgesics, opioid combination products) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Oxycodone ER is not indicated as an as-needed analgesic.Medication Safety IssuesSound-alike/look-alike issues:OxyCODONE may be confused with HYDROcodone, oxybutynin, OxyCONTIN, oxyMORphoneOxyCONTIN may be confused with MS Contin, oxybutynin, oxyMORphoneOxyFast may be confused with RoxanolRoxicodone may be confused with RoxanolHigh alert medication:The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. As reported with adult patients, unless otherwise noted.>10%:Central nervous system: Drowsiness (extended-release: 9% to 23%, extended-release, adolescents: 1% to <5%; immediate-release: ≥3%), headache (extended-release: 14%; immediate-release: ≥3%), dizziness (extended-release: 2% to 13%; immediate-release: ≥3%)Dermatologic: Pruritus (extended-release: 3% to 13%; immediate-release: ≥3%)Gastrointestinal: Nausea (extended-release: 11% to 23%; immediate-release: ≥3%), constipation (extended-release: 5% to 23%; extended-release, adolescents: 9%; immediate-release: ≥3%), vomiting (extended-release: 4% to 21%; immediate-release: 3%)Miscellaneous: Fever (extended-release: 1% to 11%; immediate-release: ≥3%)1% to 10%:Cardiovascular: Flushing (extended-release: 1% to 5%), hypertension (extended-release: 1% to 5%), orthostatic hypotension (extended-release: 1% to 5%), oxygen saturation decreased (extended-release, adolescents: 1% to <5%), edema (immediate-release: ≤5%; extended-release: <1%), tachycardia (<5%), cardiac failure (immediate-release: <3%), deep vein thrombosis (immediate-release: <3%), hypotension (<3%), palpitations (<3%; may occur with withdrawal), peripheral edema (immediate-release: <3%; extended-release: <1%), thrombophlebitis (immediate-release: <3%), vasodilation (<3%)Central nervous system: Abnormality in thinking (extended-release: 1% to 5%), dysphoria (extended-release: 1% to 5%), insomnia (1% to 5%), irritability (extended-release: 1% to 5%), twitching (extended-release: 1% to 5%), abnormal dreams (extended-release: ≤5%), anxiety (≤5%), chills (≤5%), confusion (≤5%), euphoria (extended-release: ≤5%), fatigue (extended-release: ≤5%), hypoesthesia (≤5%), migraine (≤5%), nervousness (≤5%), withdrawal syndrome (extended-release: ≤5%), agitation (<5%), pain (<5%), depression (extended-release, adolescents: 1% to <5%; extended-release, adults: <1%), lethargy (adolescents: 1% to <5%; extended-release, adults: <1%), paresthesia (extended-release, adolescents: 1% to <5%; extended-release, adults: <1%), procedural pain (extended-release, adolescents: 1% to <5%), hypertonia (<3%), neuralgia (<3%), personality disorder (immediate-release: <3%)Dermatologic: Excoriation (extended-release: 1% to 5%), diaphoresis (≤5%), hyperhidrosis (≤5%), skin rash (≤5%), skin photosensitivity (immediate-release: <3%), urticaria (<3%)Endocrine & metabolic: Hypochloremia (extended-release, adolescents: 1% to <5%), hyponatremia (extended-release: 1% to <5%), weight loss (extended-release, adolescents: 1% to <5%), hyperglycemia (≤5%), gout (immediate-release: <3%)Gastrointestinal: Diarrhea (≤6%), xerostomia (≤6%), gastritis (extended-release: 1% to 5%), hiccups (extended-release: 1% to 5%), upper abdominal pain (extended-release: 1% to 5%), abdominal pain (≤5%), anorexia (≤5%), decreased appetite (≤5%), dyspepsia (≤5%), gastroesophageal reflux disease (extended-release: ≤5%), dysphagia (immediate-release: <3%; extended-release: <1%), gingivitis (immediate-release: <3%), glossitis (immediate-release: <3%)Genitourinary: Dysuria (extended-release, adolescents: 1% to <5%; extended-release, adults: <1%), urinary retention (extended-release, adolescents: 1% to <5%; extended-release, adults: <1%), urinary tract infection (immediate-release: <3%)Hematologic & oncologic: Decreased hemoglobin (extended-release, adolescents: 1% to <5%), decreased platelet count (extended-release, adolescents: 1% to <5%), decreased red blood cells (extended-release, adolescents: 1% to <5%), febrile neutropenia (extended-release, adolescents: 1% to <5%), neutropenia (extended-release, adolescents: 1% to <5%), anemia (immediate-release: <3%), hemorrhage (immediate-release: <3%), iron deficiency anemia (immediate-release: <3%), leukopenia (immediate-release: <3%)Hepatic: Increased serum alanine aminotransferase (extended-release, adolescents: 1% to <5%)Hypersensitivity: Hypersensitivity reaction (<3%)Infection: Herpes simplex infection (immediate-release: <3%), infection (immediate-release: <3%), sepsis (immediate-release: <3%)Neuromuscular & skeletal: Asthenia (1% to 6%), limb pain (extended-release, adolescents: 1% to <5%), arthralgia (≤5%), back pain (≤5%), musculoskeletal pain (extended release: ≤5%), myalgia (≤5%), tremor (≤5%), arthritis (immediate-release: <3%), laryngospasm (immediate-release: <3%), neck pain (immediate-release: <3%), ostealgia (immediate-release: <3%), pathological fracture (immediate-release: <3%)Ophthalmic: Blurred vision (extended-release: 1% to 5%), amblyopia (immediate-release: <3%)Respiratory: Cough (≤5%), dyspnea (≤5%), oropharyngeal pain (extended-release: ≤5%), bronchitis (immediate-release: <3%), epistaxis (immediate-release: <3%), flu-like symptoms (immediate-release: <3%), laryngismus (immediate-release: <3%), pharyngitis (immediate-release: <3%), pulmonary disease (immediate-release: <3%), rhinitis (immediate-release: <3%), sinusitis (immediate-release: <3%)Miscellaneous: Seroma (extended-release, adolescents: 1% to <5%), accidental injury (<3%; extended-release: <1%)Frequency not defined:Cardiovascular: Circulatory depression, shockCentral nervous system: DepersonalizationRespiratory: Respiratory depression<1%, postmarketing, and/or case reports: Abnormal gait, aggressive behavior, amenorrhea, amnesia, chest pain, choking sensation, cholestasis, dehydration, dental caries, depression of ST segment on ECG, diverticulitis of the gastrointestinal tract (exacerbation), drug abuse, drug dependence, drug overdose (may be intentional), dysgeusia, emotional lability, eructation, exfoliative dermatitis, facial edema, flatulence, gag reflex, gastrointestinal disease, hallucination, hematuria, hyperalgesia, hyperkinesia, hypogonadism, hypotonia, impotence, increased appetite, increased gamma-glutamyl transferase, increased heart rate, increased liver enzymes, increased thirst, intestinal obstruction, lymphadenopathy, malaise, memory impairment, mood changes, neonatal withdrawal, night sweats, pharyngeal edema, polyuria, restlessness, seizure, SIADH, sleep disturbance, speech disturbance, stomatitis, stupor, suicidal ideation, suicidal tendencies, syncope, tinnitus, vertigo, visual disturbance, voice disorder, xerodermaContraindicationsHypersensitivity (eg, anaphylaxis, angioedema) to oxycodone or any component of the formulation; significant respiratory depression; hypercapnia; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; GI obstruction, including paralytic ileus (known or suspected).Documentation of allergenic cross-reactivity for opioids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to other opioids; suspected surgical abdomen (eg, acute appendicitis or pancreatitis); any disease/condition that affects bowel transit; mild pain that can be managed with other pain medications (immediate release, suppository); mild, intermittent or short duration pain that can be managed with other pain medications or acute pain (extended release); chronic obstructive airway; status asthmaticus; cor pulmonale; acute alcoholism; delirium tremens; convulsive disorders; severe CNS depression; increased cerebrospinal or intracranial pressure; head injury; monoamine oxidase (MAO) inhibitors (concomitant use or within 14 days of therapy); pregnant women or during labor and delivery; breastfeeding.Warnings/PrecautionsConcerns related to adverse effects:• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).• Constipation: May cause constipation, which may be problematic in patients with unstable angina and patients post-myocardial infarction (MI). Consider preventive measures (eg, stool softener, increased fiber) to reduce the potential for constipation.• Hypotension: May cause severe hypotension (including orthostatic hypotension and syncope); use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs that may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration. Avoid use in patients with circulatory shock.• Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (codeine, hydrocodone, hydromorphone, levorphanol, oxymorphone).• Respiratory depression: [US Boxed Warning]: Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely for respiratory depression, especially during initiation or dose escalation. Swallow ER tablets whole; crushing, chewing, or dissolving can cause rapid release and a potentially fatal dose. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. Patients and caregivers should be educated on how to recognize respiratory depression and the importance of getting emergency assistance immediately (eg, calling 911) in the event of known or suspected overdose.Disease-related concerns:• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.• Adrenocortical insufficiency: Use with caution in patients with adrenocortical insufficiency, including Addison disease; dose adjustment may be required. Long-term opioid use may cause secondary hypogonadism, which may lead to mood disorders and osteoporosis (Brennan 2013).• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; may cause constriction of sphincter of Oddi.• CNS depression/coma: Avoid use in patients with impaired consciousness or coma as these patients are susceptible to intracranial effects of CO2 retention.• Delirium tremens: Use with caution in patients with delirium tremens.• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur.• Hepatic impairment: Use with caution in patients with hepatic impairment; oxycodone clearance may decrease.• Mental health conditions: Use opioids with caution for chronic pain in patients with mental health conditions (eg, depression, anxiety disorders, post-traumatic stress disorder) due to increased risk for opioid use disorder and overdose; more frequent monitoring is recommended (Dowell [CDC 2016]).• Obesity: Use with caution in patients who are morbidly obese.• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture; dose adjustment may be required.• Psychosis: Use with caution in patients with toxic psychosis.• Renal impairment: Use with caution in patients with renal impairment; oxycodone clearance may decrease.• Respiratory disease: Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression, particularly when initiating and titrating therapy; critical respiratory depression may occur, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.• Seizures: Use with caution in patients with a history of seizure disorders; may cause or exacerbate preexisting seizures.• Sleep-related disorders: Opioid use increases the risk for sleep-related disorders (eg, central sleep apnea [CSA], hypoxemia) in a dose-dependent fashion. Use with caution for chronic pain and titrate dosage cautiously in patients with risk factors for sleep-disordered breathing (eg, heart failure, obesity). Consider dose reduction in patients presenting with CSA. Avoid opioids in patients with moderate to severe sleep-disordered breathing (Dowell [CDC 2016]).• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.Concurrent drug therapy issues:• Benzodiazepines or other CNS depressants: [US Boxed Warning]: Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of oxycodone and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosage and durations to the minimum required and follow patients for signs and symptoms of respiratory depression and sedation. Consider prescribing naloxone for emergency treatment of opioid overdose in patients taking benzodiazepines or other CNS depressants concomitantly with opioids.• CYP 3A4 interactions: [US Boxed Warning]: Use with all CYP3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitant CYP 3A4 inducer may result in increased oxycodone concentrations. Monitor patients receiving oxycodone and any CYP 3A4 inhibitor or inducer. Special populations:• Cachectic or debilitated patients: Use with caution in cachectic or debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Dose reduction may be required. Consider the use of alternative nonopioid analgesics in these patients.• Older adult: Use with caution in elderly patients; may be more sensitive to adverse effects. Use opioids for chronic pain with caution in this age group; monitor closely due to an increased potential for risks, including certain risks such as falls/fracture, cognitive impairment, and constipation. Clearance may also be reduced in older adults (with or without renal impairment) resulting in a narrow therapeutic window and increasing the risk for respiratory depression or overdose (Dowell [CDC 2016]). Consider the use of alternative nonopioid analgesics in these patients.• Neonates: Neonatal withdrawal syndrome: [US Boxed Warning]: Prolonged use of opioids during pregnancy can cause neonatal withdrawal syndrome, which may be life-threatening if not recognized and treated according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. Signs and symptoms include irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration and severity depend on the drug used, duration of use, maternal dose, and rate of drug elimination by the newborn.Dosage form specific issues:• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggest that benzoate displaces bilirubin from protein-binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.• Extended-release tablets: Tablets may be difficult to swallow and could become lodged in throat; patients with swallowing difficulties may be at increased risk. Cases of intestinal obstruction or diverticulitis exacerbation have also been reported, including cases requiring medical intervention to remove the tablet; patients with an underlying GI disease (eg, esophageal cancer, colon cancer) may be at increased risk.• Oral solutions:[US Boxed Warning]: Ensure accuracy when prescribing, dispensing, and administering oxycodone oral solution. Dosing errors due to confusion between mg and mL, and other oxycodone oral solutions of different concentrations can result in accidental overdose.Other warnings/precautions:• Abrupt discontinuation/withdrawal: Abrupt discontinuation in patients who are physically dependent on opioids has been associated with serious withdrawal symptoms, uncontrolled pain, attempts to find other opioids (including illicit), and suicide. Use a collaborative, patient-specific taper schedule that minimizes the risk of withdrawal, considering factors such as current opioid dose, duration of use, type of pain, and physical and psychological factors. Monitor pain control, withdrawal symptoms, mood changes, suicidal ideation, and for use of other substances and provide care as needed. Concurrent use of mixed agonist/antagonist analgesics (eg, pentazocine, nalbuphine, butorphanol) or partial agonist (eg, buprenorphine) analgesics may also precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists.• Abuse/misuse/diversion: [US Boxed Warning]: Use exposes patients and other users to the risks of addiction, abuse, and misuse, potentially leading to overdose and death. Assess each patient's risk prior to prescribing; monitor all patients regularly for development of these behaviors or conditions. Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Other factors associated with increased risk for misuse include younger age, concomitant depression (major), and psychotropic medication use. Consider offering naloxone prescriptions in patients with factors associated with an increased risk for overdose, such as history of overdose or substance use disorder, higher opioid dosages (≥50 morphine milligram equivalents [MME]/day orally), and concomitant benzodiazepine use (Dowell [CDC 2016]).• Accidental exposure: [US Boxed Warning]: Accidental ingestion of even one dose, especially in children, can result in a fatal overdose of oxycodone.• Appropriate use: Chronic pain (outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-based opioid use disorder treatment) in outpatient setting in adults: Opioids should not be used as first-line therapy for chronic pain management (pain >3-month duration or beyond time of normal tissue healing) due to limited short-term benefits, undetermined long-term benefits, and association with serious risks (eg, overdose, MI, auto accidents, risk of developing opioid use disorder). Preferred management includes nonpharmacologic therapy and nonopioid therapy (eg, nonsteroidal anti-inflammatory drugs, acetaminophen, certain antiseizure medications and antidepressants). If opioid therapy is initiated, it should be combined with nonpharmacologic and non-opioid therapy, as appropriate. Prior to initiation, known risks of opioid therapy should be discussed and realistic treatment goals for pain/function should be established, including consideration for discontinuation if benefits do not outweigh risks. Therapy should be continued only if clinically meaningful improvement in pain/function outweighs risks. Therapy should be initiated at the lowest effective dosage using IR opioids (instead of ER/long-acting opioids). Risk associated with use increases with higher opioid dosages. Risks and benefits should be re-evaluated when increasing dosage to ≥50 MME/day orally; dosages ≥90 MME/day orally should be avoided unless carefully justified (Dowell [CDC 2016]).• Naloxone access: Discuss the availability of naloxone with all patients who are prescribed opioid analgesics, as well as their caregivers, and consider prescribing it to patients who are at increased risk of opioid overdose. These include patients who are also taking benzodiazepines or other CNS depressants, have an opioid use disorder (OUD) (current or history of), or have experienced a previous opioid overdose. Additionally, health care providers should consider prescribing naloxone to patients prescribed medications to treat OUD; patients at risk of opioid overdose even if they are not taking an opioid analgesic or medication to treat OUD; and patients taking opioids, including methadone or buprenorphine for OUD, if they have household members, including children, or other close contacts at risk for accidental ingestion or opioid overdose. Inform patients and caregivers on options for obtaining naloxone (eg, by prescription, directly from a pharmacist, a community-based program) as permitted by state dispensing and prescribing guidelines. Educate patients and caregivers on how to recognize respiratory depression, proper administration of naloxone, and getting emergency help.• Optimal regimen: An opioid-containing analgesic regimen should be tailored to each patient's needs and based upon the type of pain being treated (acute versus chronic), the route of administration, degree of tolerance for opioids (naive versus chronic user), age, weight, and medical condition. The optimal analgesic dose varies widely among patients; doses should be titrated to pain relief/prevention.• REMS program: [US Boxed Warning]: To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, a REMS is required. Drug companies with approved opioid analgesic products must make REMS-compliant education programs available to health care providers. Health care providers are encouraged to complete a REMS-compliant education program; counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products; emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist; and consider other tools to improve patient, household, and community safety.• Surgery: Opioids decrease bowel motility; monitor for decreased bowel motility in postop patients receiving opioids. Use with caution in the perioperative setting; individualize treatment when transitioning from parenteral to oral analgesics.Metabolism/Transport EffectsSubstrate of CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potentialDrug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions programAlizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyAlvimopan: Opioid Agonists may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation.Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modificationAmphetamines: May enhance the analgesic effect of Opioid Agonists. Risk C: Monitor therapyAnticholinergic Agents: May enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor therapyAzelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combinationBlonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin.Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modificationBrimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyBromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyBromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combinationCannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products.Risk C: Monitor therapyChlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modificationChlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapyClofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapyCNS Depressants: May enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modificationCYP3A4 Inducers (Moderate): May decrease the serum concentration of OxyCODONE. Risk C: Monitor therapyCYP3A4 Inducers (Strong): May decrease the serum concentration of OxyCODONE. Risk C: Monitor therapyCYP3A4 Inhibitors (Moderate): May increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: Monitor therapyCYP3A4 Inhibitors (Strong): May enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Strong) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite oxymorphone may also be increased. Risk C: Monitor therapyDaridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modificationDesmopressin: Opioid Agonists may enhance the hyponatremic effect of Desmopressin.Risk C: Monitor therapyDexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine.Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modificationDifelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyDimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyDiuretics: Opioid Agonists may enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics.Risk C: Monitor therapyDroperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modificationEluxadoline: Opioid Agonists may enhance the constipating effect of Eluxadoline.Risk X: Avoid combinationFexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combinationFlunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine.Risk X: Avoid combinationFlunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam.Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modificationFusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combinationGastrointestinal Agents (Prokinetic): Opioid Agonists may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).Risk C: Monitor therapyHydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modificationKava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyKratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combinationLemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modificationLisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyLofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyMagnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyMethotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants.Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modificationMetoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyMetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE.Risk C: Monitor therapyMinocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyMonoamine Oxidase Inhibitors: OxyCODONE may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome.Risk X: Avoid combinationNalmefene: May diminish the therapeutic effect of Opioid Agonists. Management: Avoid the concomitant use of oral nalmefene and opioid agonists. Discontinue oral nalmefene 1 week prior to any anticipated use of opioid agonists. If combined, larger doses of opioid agonists will likely be required. Risk D: Consider therapy modificationNaltrexone: May diminish the therapeutic effect of Opioid Agonists. Management: Seek therapeutic alternatives to opioids.See full drug interaction monograph for detailed recommendations. Risk X: Avoid combinationNefazodone: Opioid Agonists (metabolized by CYP3A4) may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Opioid Agonists (metabolized by CYP3A4).Management: If concomitant use of opioid agonists that are metabolized by CYP3A4 and nefazodone is necessary, consider dose reduction of the opioid until stable drug effects are achieved. Monitor for increased opioid effects and serotonin syndrome/serotonin toxicity. Risk D: Consider therapy modificationOlopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combinationOpioids (Mixed Agonist / Antagonist): May diminish the analgesic effect of Opioid Agonists. Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Risk X: Avoid combinationOrphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine.Risk X: Avoid combinationOxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combinationParaldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde.Risk X: Avoid combinationPegvisomant: Opioid Agonists may diminish the therapeutic effect of Pegvisomant.Risk C: Monitor therapyPHENobarbital: May enhance the CNS depressant effect of OxyCODONE. PHENobarbital may decrease the serum concentration of OxyCODONE. Management: Avoid use of oxycodone and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined. Risk D: Consider therapy modificationPiribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil.Risk C: Monitor therapyPramipexole: CNS Depressants may enhance the sedative effect of Pramipexole.Risk C: Monitor therapyPrimidone: May enhance the CNS depressant effect of OxyCODONE. Primidone may decrease the serum concentration of OxyCODONE. Management: Avoid use of oxycodone and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a strong CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined. Risk D: Consider therapy modificationProcarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyRamosetron: Opioid Agonists may enhance the constipating effect of Ramosetron.Risk C: Monitor therapyRopeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased.Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modificationROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole.Risk C: Monitor therapyRotigotine: CNS Depressants may enhance the sedative effect of Rotigotine.Risk C: Monitor therapyRufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapySamidorphan: May diminish the therapeutic effect of Opioid Agonists. Risk X: Avoid combinationSerotonergic Agents (High Risk): Opioid Agonists (metabolized by CYP3A4) may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome.Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapySincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide.Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modificationSomatostatin Analogs: Opioid Agonists may diminish the analgesic effect of Somatostatin Analogs. Opioid Agonists may enhance the analgesic effect of Somatostatin Analogs.Risk C: Monitor therapySuccinylcholine: May enhance the bradycardic effect of Opioid Agonists. Risk C: Monitor therapySuvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant.Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary.Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modificationThalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide.Risk X: Avoid combinationValerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapyZolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem.Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg formen who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modificationDietary ConsiderationsInstruct patient to avoid high-fat meals when taking some products (food has no effect on the reformulated OxyContin).Reproductive ConsiderationsLong-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction or infertility (Brennan 2013).Pregnancy ConsiderationsOxycodone crosses the placenta (Kokki 2012).According to some studies, maternal use of opioids may be associated with birth defects (including neural tube defects, congenital heart defects, and gastroschisis), poor fetal growth, stillbirth, and preterm delivery (CDC [Dowell 2016]).[US Boxed Warning]: Prolonged use of oxycodone during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. If chronic opioid exposure occurs in pregnancy, adverse events in the newborn (including withdrawal) may occur (Chou 2009). Symptoms of neonatal abstinence syndrome (NAS) following opioid exposure may be autonomic (eg, fever, temperature instability), gastrointestinal (eg, diarrhea, vomiting, poor feeding/weight gain), or neurologic (eg, high-pitched crying, hyperactivity, increased muscle tone, increased wakefulness/abnormal sleep pattern, irritability, sneezing, seizure, tremor, yawning) (Dow 2012; Hudak 2012). Mothers who are physically dependent on opioids may give birth to infants who are also physically dependent. Opioids may cause respiratory depression and psycho-physiologic effects in the neonate; newborns of mothers receiving opioids during labor should be monitored.Oxycodone is not commonly used to treat pain during labor and immediately postpartum (ACOG 209 2019) or chronic noncancer pain in pregnant women or those who may become pregnant (CDC [Dowell 2016]; Chou 2009).Monitoring ParametersAcute pain (short-term): Pain relief, respiratory rate, mental status, blood pressure; stool output; signs of misuse, abuse, and addiction.Chronic pain (long-term therapy outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-assisted treatment for opioid use disorder): Evaluate benefits/risks of opioid therapy within 1 to 4 weeks of treatment initiation and with dose increases. Reevaluate benefits/risks every 3 months during therapy or more frequently in patients at increased risk of overdose or opioid use disorder. Urine drug testing is recommended prior to initiation and with consideration for rechecking at least yearly (includes controlled prescription medications and illicit drugs of abuse). State prescription drug monitoring program (PDMP) data should be reviewed by clinicians prior to initiation and periodically during therapy (frequency ranging from every prescription to every 3 months) (CDC [Dowell 2016]).Mechanism of ActionBinds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depressionPharmaco*kinetics (Adult data unless noted)Onset of action: Pain relief: Immediate release: 10 to 15 minutes.Peak effect: Immediate release: 0.5 to 1 hour.Duration: Immediate release: 3 to 6 hours; Extended release: ≤12 hours.Distribution: Vd: Children 2 to 10 years: 2.1 L/kg (range: 1.2 to 3.7 L/kg); Adults: 2.6 L/kg; distributed to skeletal muscle, liver, intestinal tract, lungs, spleen, and brain.Protein binding: 38% to 45%.Metabolism: Hepatically via CYP3A4 to noroxycodone (has weak analgesic activity), noroxymorphone, and alpha- and beta-noroxycodol. CYP2D6 mediated metabolism produces oxymorphone (has analgesic activity; low plasma concentrations [<15%]), alpha- and beta-oxymorphol.Bioavailability: Extended release tablet, immediate release: 60% to 87%; Extended release capsule is not bioequivalent to extended release tablet; however AUC, is similar in a fed state.Half-life:Apparent: Immediate release: 3.2 to ~4 hours; Extended release tablet: 4.5 hours; Extended release capsule: 5.6 hours.Elimination: Children 2 to 10 years: 1.8 hours (range: 1.2 to 3 hours); Adults: 3.7 hours.Adults with CrCl <60 mL/minute: Half-life increases by 1 hour, but peak oxycodone concentrations increase by 50% and AUC increases by 60%.Adults with mild to moderate hepatic impairment: Half-life increases by 2.3 hours, peak oxycodone concentrations increase by 50%, and AUC increases by 95%.Time to peak, plasma: Immediate release: 1.2 to 1.9 hours; Extended release: 4 to 5 hours.Excretion: Urine: (~10% as parent; ~65% as metabolites [noroxycodone (23%, active), oxymorphone (10%, active), noroxymorphone (14%, weakly active), reduced metabolites (≤18%)]) (Kinnunen 2019).Pharmaco*kinetics: Additional ConsiderationsAltered kidney function: Higher peak plasma oxycodone (50%), and noroxycodone (20%), higher AUC for oxycodone (60%), noroxycodone (50%), and oxymorphone (40%) in patients with CrCl <60 mL/minute. There is an increased half-life elimination for oxycodone elimination of only 1 hour.Hepatic function impairment: Peak plasma oxycodone and noroxycodone concentrations 50% and 20% higher; AUC values are 95% and 65% higher, respectively, in mild to moderate hepatic impairment. Oxymorphone peak plasma concentration and AUC values are lower by 30% and 40%. The half-life elimination for oxycodone is increased by 2.3 hours.Additional InformationOxyContin tablets deliver medication over 12 hours; release is pH independent. Equianalgesic doses: oral oxycodone 30 mg = morphine 10 mg IM = single oral dose morphine 60 mg or chronic dosing oral morphine 30 mg. Note: Not appropriate for OxyContin initial dose calculation.Oxaydo utilizes Acura Pharmaceutical's Aversion technology which may help discourage misuse and abuse potential. Reduced abuse potential of Oxaydo compared to other immediate-release oxycodone tablet formulations has not been proven; the FDA has required a post-approval epidemiological study to determine whether the formulation actually results in a decrease of misuse/abuse. In one clinical trial in nondependent recreational opioid users, the "drug-liking" responses and safety of crushed Oxaydo tablets were compared to crushed immediate-release oxycodone tablets following the self-administered intranasal use. A small difference in "drug-liking" scores was observed, with lower scores reported in the crushed Oxaydo group. In regard to safety, there was an increased incidence of nasopharyngeal and facial adverse events in the Oxaydo group. In addition, there was decreased ability in the Oxaydo group to completely administer the 2 crushed Oxaydo tablets intranasally within a set time period. However, whether these differences translate into a significant clinical difference is unknown. Of note, pharmaco*kinetic studies showed that Oxaydo is bioequivalent with oxycodone immediate-release tablets with no differences in Tmax and half-life when administered in the fasted state.Pricing: USCapsule ER 12 Hour Abuse-Deterrent (Xtampza ER Oral)9 mg (per each): $7.1013.5 mg (per each): $10.4518 mg (per each): $13.2527 mg (per each): $18.4336 mg (per each): $22.69Capsules (oxyCODONE HCl Oral)5 mg (per each): $1.84 - $1.85Concentrate (oxyCODONE HCl Oral)100 mg/5 mL (per mL): $4.17 - $12.33Solution (oxyCODONE HCl Oral)5 mg/5 mL (per mL): $1.05 - $1.73Tablet Abuse-Deterrent (RoxyBond Oral)5 mg (per each): $13.1215 mg (per each): $15.8830 mg (per each): $21.40Tablet ER 12 Hour Abuse-Deterrent (oxyCODONE HCl ER Oral)10 mg (per each): $3.02 - $5.0320 mg (per each): $5.64 - $9.3740 mg (per each): $8.36 - $16.0580 mg (per each): $15.73 - $28.01Tablet ER 12 Hour Abuse-Deterrent (OxyCONTIN Oral)10 mg (per each): $5.7415 mg (per each): $8.4420 mg (per each): $10.6930 mg (per each): $14.8840 mg (per each): $18.3160 mg (per each): $25.9380 mg (per each): $31.96Tablets (Oxaydo Oral)5 mg (per each): $11.707.5 mg (per each): $17.53Tablets (oxyCODONE HCl Oral)5 mg (per each): $0.08 - $0.6210 mg (per each): $0.15 - $1.4515 mg (per each): $0.12 - $2.3720 mg (per each): $0.27 - $2.3230 mg (per each): $0.18 - $4.49Tablets (Roxicodone Oral)15 mg (per each): $6.2330 mg (per each): $12.23Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalAbtard (GB);Alnagon (RO);Dancex (IE);Endone (AU);Epethinan (IE);Ircodon (KR);Lynlor (GB);M-Oxy (PE);Orionox (FI, NO);Oxinovag (AR);Oxycod (IL);OxyContin (AR, AT, BR, CH, CL, CO, CR, CY, CZ, DK, DO, EC, EE, ES, FI, GB, GT, HK, HN, IE, IL, IT, MY, NI, NL, NO, NZ, PA, PE, PH, PL, PT, SE, SG, SV, VE);Oxycontin (BB, BH, CN, HR, HU, IS, LB, LU, RO, SI, SK, TR, TW, VN, ZA);Oxycontin CR (KR);Oxycontin LP (FR);Oxycontin Neo (PH);Oxyduo (PL);Oxyfast (JP);Oxygesic (DE);Oxyneo (ID, VN);Oxynorm (AT, AU, BE, CH, CY, DK, EG, ES, FI, FR, GB, HK, ID, IE, IS, MY, NO, NZ, PH, SE, SG, TR, TW, ZA);OxyNorm (JP);Oxynorm IV (SG);Plexicodim (MX);Proladone (AU);Reltebon (GB, HU);Targin (DE, IL)For country code abbreviations (show table)Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319. [PubMed 11487763]American College of Obstetricians and Gynecologists (ACOG). ACOG practice bulletin no. 209: obstetric analgesia and anesthesia. Obstet Gynecol. 2019;133(3):e208-e225. [PubMed 30801474]American Pain Society (APS). Pain assessment and management initiative (PAMI) dosing guide. Updated November 2016b.American Pain Society (APS). Principles of analgesic use. Seventh edition. 2016a.Anderson DT, Fritz KL, Muto JJ. Oxycontin: the concept of a "ghost pill" and the postmortem tissue distribution of oxycodone in 36 cases. J Anal Toxicol. 2002;26(7):448-459. [PubMed 12422999]APO-Oxycodone CR (oxycodone) [product monograph]. Toronto, Ontario, Canada: Apotex Inc; December 2021.Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007.Association of Paediatric Anaesthetists of Great Britain and Ireland (APA). Good practice in postoperative and procedural pain management, 2nd edition. Paediatr Anaesth. 2012;22(Suppl 1):1-79.Azhar A, Kim YJ, Haider A, et al. Response to oral immediate-release opioids for breakthrough pain in patients with advanced cancer with adequately controlled background pain. Oncologist. 2019;24(1):125-131. doi:10.1634/theoncologist.2017-0583 [PubMed 30254187]Based on expert opinion.Berde CB, Sethna NF. Analgesics for the treatment of pain in children. N Engl J Med. 2002;347(14):1094-1103. [PubMed 12362012]Berna C, Kulich RJ, Rathmell JP. Tapering long-term opioid therapy in chronic noncancer pain: evidence and recommendations for everyday practice. Mayo Clin Proc. 2015;90(6):828-842. doi:10.1016/j.mayocp.2015.04.003 [PubMed 26046416]Brennan MJ. The effect of opioid therapy on endocrine function. Am J Med. 2013;126(3)(suppl 1):S12-S18. doi:10.1016/j.amjmed.2012.12.001 [PubMed 23414717]Carr D. Management of acute pain in the patient chronically using opioids for non-cancer pain. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 11, 2021.Carvalho B, Sutton CD. Post-cesarean delivery analgesia. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 5, 2021.Centers for Disease Control and Prevention (CDC). Common elements in guidelines for prescribing opioids for chronic pain. https://www.cdc.gov/drugoverdose/pdf/common_elements_in_guidelines_for_prescribing_opioids-a.pdf. Published 2015. Accessed September 13, 2018.Centers for Disease Control and Prevention (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm [PubMed 6810084]Cheung CW, Ching Wong SS, Qiu Q, Wang X. Oral oxycodone for acute postoperative pain: a review of clinical trials. Pain Physician. 2017;20(2S):SE33-SE52. [PubMed 28226340]Chou R, Fanciullo GJ, Fine PG, et al, "Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain," J Pain, 2009, 10(2):113-30. [PubMed 19187889]Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016;17(2):131-157. doi:10.1016/j.jpain.2015.12.008 [PubMed 26827847]Coté CJ, Lerman J, Anderson B, eds. A Practice of Anesthesia for Infants and Children. 6th ed. Elsevier; 2019.Davison SN. Clinical pharmacology considerations in pain management in patients with advanced kidney failure. Clin J Am Soc Nephrol. 2019;14(6):917-931. doi:10.2215/CJN.05180418 [PubMed 30833302]Debono M, Chan S, Rolfe C, Jones TH. Tramadol-induced adrenal insufficiency. Eur J Clin Pharmacol. 2011; 67:865-867. doi:10.1007/s00228-011-0992-9 [PubMed 21243342]Dow K, Ordean A, Murphy-Oikonen J, et al, "Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario," J Popul Ther Clin Pharmacol, 2012, 19(3):e488-506. [PubMed 23241498]Dowell D. CDC guideline for prescribing opioids for chronic pain clarification [written communication]. Atlanta, GA: Centers for Disease Control and Prevention; February 28, 2019.Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016. MMWR Recomm Rep. 2016;65(1):1-49. doi:10.15585/mmwr.rr6501e1 [PubMed 26987082]Foral PA, Ineck JR, Nystrom KK. Oxycodone accumulation in a hemodialysis patient. South Med J. 2007;100(2):212-214. doi:10.1097/01.smj.0000242876.45747.0a [PubMed 17330696]Gallagher RM, Welz-Bosna M, Gammaitoni A. Assessment of dosing frequency of sustained-release opioid preparations in patients with chronic nonmalignant pain. Pain Med. 2007;8(1):71-74. [PubMed 17244106]Hill MV, Stucke RS, McMahon ML, Beeman JL, Barth RJ Jr. An educational intervention decreases opioid prescribing after general surgical operations. Ann Surg. 2018;267(3):468-472. doi:10.1097/SLA.0000000000002198 [PubMed 28267689]Hudak ML, Tan RC, Committee on Drugs, et al, "Neonatal Drug Withdrawal," Pediatrics, 2012, 129(2):e540-60. [PubMed 22291123]"Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics (AAP) Committee on Drugs. Pediatrics. 1997;99(2):268-278. [PubMed 9024461]Kinnunen M, Piirainen P, Kokki H, Lammi P, Kokki M. Updated clinical pharmaco*kinetics and pharmacodynamics of oxycodone. Clin Pharmaco*kinet. 2019;58(6):705-725. doi:10.1007/s40262-018-00731-3 [PubMed 30652261]Kirvela M, Lindgren L, Seppala T, Olkkola KT. The pharmaco*kinetics of oxycodone in uremic patients undergoing renal transplantation. J Clin Anesth. 1996;8(1):13-18. doi:10.1016/0952-8180(95)00092-5 [PubMed 8695073]Kokki M, Franco MG, Raatikainen K, et al. Intravenous oxycodone for pain relief in the first stage of labour--maternal pharmaco*kinetics and neonatal exposure. Basic Clin Pharmacol Toxicol. 2012;111(3):182-188. [PubMed 22448718]Koncicki HM, Unruh M, Schell JO. Pain management in CKD: a guide for nephrology providers. Am J Kidney Dis. 2017;69(3):451-460. doi:10.1053/j.ajkd.2016.08.039 [PubMed 27881247]Lam J, Kelly L, Ciszkowski C, et al. Central nervous system depression of neonates breastfed by mothers receiving oxycodone for postpartum analgesia. J Pediatr. 2012;160(1):33-37. [PubMed 21880331]Leuppi-Taegtmeyer A, Duthaler U, Hammann F, et al. Pharmaco*kinetics of oxycodone/naloxone and its metabolites in patients with end-stage renal disease during and between haemodialysis sessions. Nephrol Dial Transplant. 2019;34(4):692-702. doi:10.1093/ndt/gfy285 [PubMed 30189012]Marcus DA, Glick RM. Sustained-release oxycodone dosing survey of chronic pain patients. Clin J Pain. 2004;20(5):363-366. [PubMed 15322444]Mariano ER. Management of acute perioperative pain. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 12, 2021.Martin E, Vickers B, Landau R, Reece-Stremtan S. ABM clinical protocol #28, peripartum analgesia and anesthesia for the breastfeeding mother. Breastfeed Med. 2018;13(3):164-171. [PubMed 29595994]Nicholson B, Ross E, Sasaki J, Weil A. Randomized trial comparing polymer-coated extended-release morphine sulfate to controlled-release oxycodone HCl in moderate to severe nonmalignant pain. Curr Med Res Opin. 2006;22(8):1503-1514. [PubMed 16870075]Oxaydo (oxycodone) [prescribing information]. Wayne, PA: Zyla Life Sciences US Inc; March 2021.OxyContin (oxycodone) extended-release tablets [prescribing information]. Stamford, CT: Purdue Pharma LP; October 2021.Oxycodone hydrochloride capsules [prescribing information]. Allentown, PA: Genus Lifesciences Inc; July 2021.Oxycodone hydrochloride 1 mg/mL oral solution [prescribing information]. Allentown, PA: Genus Lifesciences Inc; July 2021.Oxycodone hydrochloride oral solution [prescribing information]. Berkeley Heights, NJ: Hikma Pharmaceuticals USA Inc; July 2021.Oxycodone hydrochloride oral solution [prescribing information]. Largo, FL: VistaPharm; March 2021.Oxycodone hydrochloride tablet [prescribing information]. Coventry, RI: Rhodes Pharmaceuticals LP; March 2021.Oxy IR (oxycodone) [product monograph]. Pickering, Ontario, Canada: Purdue Pharma; August 2020.Oxyneo (oxycodone) controlled release tablets [product monograph]. Toronto, Ontario, Canada: Purdue Pharma; July 2022.Paice JA, Ferrell B. The management of cancer pain. CA Cancer J Clin. 2011;61(3):157-182. doi:10.3322/caac.20112 [PubMed 21543825]Pain Assessment and Management Initiative. Pain management & dosing guide. https://pami.emergency.med.jax.ufl.edu/wordpress/files/2020/09/PAMI-Dosing-Guide-Nov.2.2020.pdf. Updated November 2020. Accessed October 12, 2021.Pino CA, Wakerman SE. Prescription of opioids for acute pain in opioid naïve patients. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 25, 2022.Portenoy RK, Mehta Z, Ahmed E. Cancer pain management with opioids: optimizing analgesia. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 12, 2021.Rakoski M, Goyal P, Spencer-Safier M, Weissman J, Mohr G, Volk M. Pain management in patients with cirrhosis. Clin Liver Dis (Hoboken). 2018;11(6):135-140. doi:10.1002/cld.711 [PubMed 30992804]Reece-Stremtan S, Campos M, Kokajko L; Academy of Breastfeeding Medicine. ABM clinical protocol #15: analgesia and anesthesia for the breastfeeding other, revised 2017. Breastfeed Med. 2017;12(9):500-506. [PubMed 29624435]Refer to manufacturer's labeling.Rosenquist R. Use of opioids in the management of chronic non-cancer pain. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 31, 2022.Roxicodone (oxycodone) [prescribing information]. Webster Groves, MO: SpecGx LLC; August 2022.Roxybond (oxycodone) [prescribing information]. Princeton, NJ: Protega Pharmaceuticals LLC; February 2022.Sachs HC, Committee On Drugs. The transfer of drugs and therapeutics into human breast milk: an update on selected topics. Pediatrics. 2013;132(3):e796-809. [PubMed 23979084]Seaton S, Reeves M, McLean S. Oxycodone as a component of multimodal analgesia for lactating mothers after Caesarean section: relationships between maternal plasma, breast milk and neonatal plasma levels. Aust N Z J Obstet Gynaecol. 2007;47(3):181-185. [PubMed 17550483]Sevarino KA. Medically supervised opioid withdrawal during treatment for addiction. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 12, 2021.Sulton-Villavasso C, Austin CA, Patra KP, et al. Index of suspicion. Case 1: Infant who has respiratory distress. Case 2: Abnormal behavior, seizures, and altered sensorium in a 7-year-old boy. Case 3: Fever and dysphagia in a 4-year-old girl. Pediatr Rev. 2012;33(6):279-284. [PubMed 22659261]Supeudol (oxycodone) [product monograph]. Boucherville, Quebec, Canada: Sandoz Canada Inc; September 2019.Tawfic QA, Bellingham G. Postoperative pain management in patients with chronic kidney disease. J Anaesthesiol Clin Pharmacol. 2015;31(1):6-13. doi:10.4103/0970-9185.150518 [PubMed 25788766]Tran BW, Kohan LR, Vorenkamp KE. Postoperative oxycodone toxicity in a patient with chronic pain and end-stage renal disease. A A Case Rep. 2015;4(4):44-46. doi:10.1213/XAA.0000000000000115 [PubMed 25689360]US Department of Health and Human Services (HHS). HHS guide for clinicians on the appropriate dosage reduction or discontinuation of long-term opioid analgesics. https://www.hhs.gov/opioids/sites/default/files/2019-10/Dosage_Reduction_Discontinuation.pdf. Updated October 2019. Accessed October 12, 2021.Weinberg DS, Inturrisi CE, Reidenberg B, et al. Sublingual absorption of selected opioid analgesics. Clin Pharmacol Ther. 1988;44(3):335-342. doi:10.1038/clpt.1988.159 [PubMed 2458208]World Health Organization (WHO). Breastfeeding and maternal medication, recommendations for drugs in the eleventh WHO model list of essential drugs. 2002. Available at http://www.who.int/maternal_child_adolescent/documents/55732/en/Xtampza ER (oxycodone) [prescribing information]. Cincinnati, OH: Patheon Pharmaceuticals; March 2021.Topic 12666 Version 632.0

CloseImpact of addition of immune checkpoint inhibitors to neoadjuvant chemotherapy in triple-negative breast cancerImpact of addition of immune checkpoint inhibitors to neoadjuvant chemotherapy in triple-negative breast cancer Study (reference) Chemotherapy regimen Subgroup IT agent (target) Control EFS results (IT versus control) Number pCR* (%) Number pCR* (%)   Pembrolizumab (PD-1) Placebo   KEYNOTE-522[1,2] Weekly pacl*taxel with carboplatin (weekly or every 3 weeks) for 12 weeks followed by doxorubicin or epirubicin and cyclophosphamide for 4 cycles All 784 65 390 51 At median follow-up of 39 months, 3-year EFS 84 versus 77% (HR 0.63, 95% CI 0.48-0.82) PD-L1+ 656 69 317 55 PD-L1– 127 45 69 30 I-SPY2[3] Weekly pacl*taxel for 12 weeks followed by doxorubicin and cyclophosphamide for 4 cycles All 28 60 80 22 Not reported   Atezolizumab (PD-L1) Placebo   Impassion031[4] Weekly nabpacl*taxel for 12 weeks followed by doxorubicin and cyclophosphamide for 4 cycles All 165 58 168 41 At approximately 20 months' median follow-up, EFS not reached (HR 0.76, 95% CI 0.4-1.44) PD-L1+ 77 69 75 49 PD-L1– 88 48 93 34   Atezolizumab (PD-L1) None   NeoTRIPaPDL1[5] Nabpacl*taxel and carboplatin days 1 and 8 every 21 days for 8 cycles All 138 44 142 41 Not reported PD-L1+ 79 52 77 48 PD-L1– 59 32 65 32   Durvalumab (PD-L1) Placebo   GeparNUEVO[6,7] Weekly nabpacl*taxel for 12 weeks followed epirubicin and cyclophosphamide for 4 cycles All 88 53 86 44 At median follow-up of 42 months, 3-year iDFS 85 versus 77% (HR 0.54, 95% CI 0.27-1.09) PD-L1+ 69 58 69 51 PD-L1– 11 44 9 18 Window¶ 59 61 58 41IT: immunotherapy; pCR: pathologic complete response; PD-1: programmed cell death protein 1; EFS: event-free survival; PD-L1: programmed cell death ligand 1; HR: hazard ratio; iDFS: invasive disease-free survival.* pCR: ypT0/isN0.¶ The first 117 patients treated on GeparNeuvo received a single dose of either durvalumab or placebo two weeks before starting neoadjuvant chemotherapy with the same agent; this was omitted after the study's independent data monitoring committee expressed concern about the delay in the start of chemotherapy; another 57 patients were subsequently treated without this "window" treatment.References:Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med 2020; 382:810.Schmid P, Cortes J, Dent R, et al.KEYNOTE-522: Phase III study of neoadjuvant pembrolizumab + chemotherapy versus placebo + chemotherapy, followed by adjuvant pembrolizumab versus. placebo for early-stage TNBC. Ann Oncol 2021; ESMO #VP7-2021.Nanda R, Liu MC, Yau C, et al. Effect of pembrolizumab plus neoadjuvant chemotherapy on pathologic complete response in women with early-stage breast cancer: An analysis of the ongoing phase 2 adaptively randomized I-SPY2 trial. JAMA Oncol 2020; 6:676.Mittendorf EA, Zhang H, Barrios CH, et al. Neoadjuvant atezolizumab in combination with sequential nabpacl*taxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): A randomised, double-blind, phase 3 trial. Lancet 2020; 396:1090.Gianni L, Huang CS, Egle D, et al. Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple-negative, early high-risk and locally advanced breast cancer. NeoTRIPaPDL1 Michelangelo randomized study. Cancer Res 2019; 80S: SABCS #GS3-04.Loibl S, Untch M, Burchardi N, et al. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: Clinical results and biomarker analysis of GeparNuevo study. Ann Oncol 2019; 30:1279.Loibl S, Schneeweiss A, Huober JB, et al. Durvalumab improves long-term outcome in TNBC: Results from the phase II randomized GeparNUEVO study investigating neoadjuvant durvalumab in addition to an anthracycline/taxane based neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC). J Clin Oncol 2021; 39S: ASCO #506.Graphic 129974 Version 2.0

CloseAllopurinol: Drug informationAllopurinol: Drug information(For additional information see "Allopurinol: Patient drug information" and see "Allopurinol: Pediatric drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USAloprim;ZyloprimBrand Names: CanadaAG-Allopurinol;APO-Allopurinol;GEN-Allopurinol;JAMP-Allopurinol;Mar-Allopurinol;ZyloprimPharmacologic CategoryAntigout Agent;Xanthine Oxidase InhibitorDosing: AdultNote: Before prescribing allopurinol, testing for the HLA-B*5801 allele in patients at elevated risk for developing severe cutaneous adverse reactions (SCAR) (patients of Asian descent [eg, Korean, Han Chinese, Thai] and African American patients) is recommended (Ref). A negative HLA-B*5801 genetic test, however, does not entirely rule out the possibility of allopurinol-associated SCAR, so patients should still be appropriately monitored for SCAR, as well as other forms of hypersensitivity (Ref). Use should be avoided in any patient testing positive for the allele (Ref).Gout, treatmentGout, treatment (chronic urate-lowering therapy): Oral: Note: Urate-lowering therapy may be initiated during a gout flare or after the flare subsides; concomitant pharmacologic prophylaxis with colchicine, NSAIDS, or a glucocorticoid is recommended for at least the first 3 to 6 months to decrease flare activity (Ref).Initial: 100 mg once daily (Ref).Dosage adjustments: Titrate in 100 mg increments every 2 to 4 weeks to achieve the desired serum uric acid level (Ref).Maintenance: Doses ≥300 mg/day are usually needed to reach the desired uric acid target; doses up to 800 mg/day may be required (Ref).Maximum: 800 mg/dayFrequency of administration: Once daily in a single dose or in 2 or 3 divided doses. Note: The manufacturer's labeling recommends doses >300 mg be given in divided doses; however, most experts prescribe a single daily dose, regardless of total dose administered, except during a brief period (eg, when initiating or titrating therapy) when divided doses may help improve GI tolerability (Ref).Nephrolithiasis, prevention of recurrent calcium or uric acid stonesNephrolithiasis, prevention of recurrent calcium or uric acid stones: Due to calcium oxalate stones: Patients with hyperuricosuria (who continue to have active disease despite attempted dietary modification): Oral: 300 mg/day, usually given in a single daily dose but may be given in 2 or 3 divided doses, if needed, to improve GI tolerability (Ref).Due to uric acid stones (off-label use): Oral: 300 mg/day, usually given in a single daily dose but may be given in 2 or 3 divided doses, if needed, to improve GI tolerability; use is reserved for patients who continue to have active disease despite urinary alkalinization therapy and increased hydration (Ref).Tumor lysis syndrome, preventionTumor lysis syndrome, prevention: Patients at intermediate risk for tumor lysis syndrome (TLS) and without preexisting hyperuricemia (serum uric acid ≥8 mg/dL [476 micromol/L]):Note: Aggressive IV hydration should always be initiated prior to cytotoxic therapy in patients at elevated risk for TLS (Ref).Oral: 300 mg/m2/day or 10 mg/kg/day, given in 3 divided doses every 8 hours (maximum: 800 mg/day). Begin therapy 1 to 2 days before the start of induction chemotherapy and may continue for up to 3 to 7 days after chemotherapy until normalization of laboratory evidence of TLS (eg, serum uric acid, serum LDH) (Ref).IV: 200 to 400 mg/m2/day, given in a single daily dose or in 2 or 3 divided doses (maximum: 600 mg/day). Begin therapy 1 to 2 days before the start of induction chemotherapy and may continue for 3 to 7 days after chemotherapy until normalization of laboratory evidence of TLS (eg, serum uric acid, serum LDH) (Ref).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultThe renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.Note: Renal impairment, particularly when a higher allopurinol starting dose and/or concomitant diuretics are used, is a risk factor for allopurinol hypersensitivity syndrome (AHS), a rare but potentially life-threatening systemic syndrome (Ref). In addition, the HLA-B*5801 allele is associated with an increased risk of allopurinol-induced severe cutaneous adverse reactions; patients of Korean, Han Chinese, or Thai descent are at increased risk for carrying this allele. Avoid allopurinol in any patient testing positive for this allele (Ref).To minimize the risk of AHS in patients with renal impairment (in the absence of the HLA-B*5801 allele or in those not at high risk for carrying this allele), the following dosage adjustments are recommended:Gout, treatment (chronic urate-lowering therapy): Oral:Altered kidney function:eGFR >60 mL/minute: No dosage adjustment necessary (Ref).eGFR ≤60 mL/minute:Initial: <100 mg daily (Ref); to lower the risk of AHS, some experts recommend not exceeding an initial dose of ~1.5 mg of allopurinol per mL/minute of eGFR (eg, for an eGFR of 50 mL/minute/1.73 m2, the initial dose should not exceed 75 mg daily; see table for suggested initial doses) (Ref).Allopurinol: Suggested Initial Doses in Kidney ImpairmentaeGFR mL/minute/1.73 m2Suggested initial doseaACR (FitzGerald 2020); Perez-Ruiz 2022; Stamp 2012; Vargas-Santos 2017.>30 to 6050 mg daily>15 to 3050 mg every other day5 to 1550 mg twice weekly<550 mg once weeklyTitration and maintenance: Gradually increase dose in ≤100 mg/day increments every 2 to 4 weeks; use of lower dose increments (ie, ≤50 mg/day) and longer intervals (ie, ≥4 weeks) may be preferred (Ref). Some experts delay the initial dose increase for 1 to 2 months until after peak risk for AHS has passed (Ref). Titrate to the minimum daily dose necessary to achieve goal urate-lowering effect. Doses >300 mg daily may be considered with appropriate patient education and monitoring for potential toxicity (eg, rash, pruritus, elevated transaminases) (Ref). If desired serum uric acid level cannot be achieved, conversion to an alternative agent may be considered (Ref).Hemodialysis, intermittent (thrice weekly): Dialyzable (oxypurinol): ~39% to 50% (Ref).Initial: 100 mg 3 times weekly administered post-dialysis (Ref).Titration and maintenance: Gradually increase dose in ≤50 mg/day increments (eg, 150 mg 3 times weekly) every 2 to 5 weeks. Some experts delay the initial dose increase for 1 to 2 months until after peak risk for AHS has passed (Ref). Titrate to the minimum dose necessary to achieve goal urate-lowering effect (Ref). Doses >300 mg daily may be considered with appropriate patient education and monitoring for potential toxicity (eg, rash, pruritus, elevated transaminases) (Ref); doses up to ~400 mg daily have been reported (Ref).Peritoneal dialysis:Initial: 50 mg daily; gradually increase dose in ≤50 mg/day increments every 2 to 5 weeks; titrate to the minimum daily dose necessary to achieve goal urate-lowering effect (Ref). Some experts delay the initial dose increase for 1 to 2 months until after peak risk for AHS has passed (Ref). Doses >300 mg daily may be considered with appropriate patient education and monitoring for potential toxicity (eg, rash, pruritus, elevated transaminases) (Ref).Nephrolithiasis, prevention of recurrent calcium or uric acid stones: Oral: Use a lower initial dose with gradual titration (Ref); for dosing guidance refer to gout treatment renal impairment dosing recommendations; not to exceed usual adult dose for nephrolithiasis.Tumor lysis syndrome, prevention: IV, Oral: Dosage reduction of 50% is recommended in renal impairment (Ref).Dosing: Hepatic Impairment: AdultThere are no dosage adjustments provided in the manufacturer's labeling.Dosing: Pediatric(For additional information see "Allopurinol: Pediatric drug information")Note: Dosing presenting in multiple formats (mg/m2/dose, mg/m2/day, mg/kg/day, and a fixed mg dose); take extra precautions to ensure accuracy. Before prescribing allopurinol, consider testing for the HLA-B*5801 allele in patients at elevated risk for developing severe cutaneous adverse reactions (SCAR) (including Koreans with CKD ≥ stage 3 and all patients of Han Chinese or Thai descent). A negative HLA-B*5801 genetic test, however, does not entirely rule out the possibility of allopurinol-associated SCAR, so patients should still be appropriately monitored for SCAR, as well as other forms of hypersensitivity (Ref).Hyperuricemia associated with chemotherapy managementHyperuricemia associated with chemotherapy management: Maintain adequate hydration; begin allopurinol 1 to 2 days before initiation of induction chemotherapy; may continue for 3 to 7 days after chemotherapy (Ref); daily doses >300 mg should be administered in divided doses:Oral:Manufacturer's labeling:Children <6 years: 150 mg daily.Children 6 to 10 years: 300 mg daily.Children >10 years and Adolescents: 600 to 800 mg daily for 2 to 3 days in 2 to 3 divided doses.Alternate dosing: Tumor lysis syndrome; intermediate-risk: Limited data available (Ref): Infants, Children, and Adolescents:Weight-directed dosing: 10 mg/kg/day divided every 8 hours; maximum daily dose: 800 mg/day.BSA-directed dosing: 50 to 100 mg/m2/dose every 8 hours; maximum daily dose: 300 mg/m2/day.IV: For patients unable to tolerate oral therapy (BSA-directed dosing):Manufacturer's labeling: Children and Adolescents: Initial: 200 mg/m2/day administered once daily or in equally divided doses at 6-, 8-, or 12-hour intervals.Alternate dosing: Tumor lysis syndrome; intermediate-risk: Limited data available: Infants, Children, and Adolescents: 200 to 400 mg/m2/day in 1 to 3 divided doses; maximum daily dose: 600 mg/day (Ref).Hyperuricemia associated with inborn errors of purine metabolismHyperuricemia associated with inborn errors of purine metabolism (Lesch-Nyhan syndrome): Limited data available: Oral: Infants, Children, and Adolescents: Initial: 5 to 10 mg/kg/day; adjust dose to maintain a high-normal serum uric acid concentration and a urinary uric acid/creatinine ratio <1; reported range: 3.7 to 9.7 mg/kg/day; usual maximum daily dose: 600 mg/day (Ref).Recurrent calcium oxalate renal stonesRecurrent calcium oxalate renal stones (including glycogen storage disease): Limited data available: Oral: Children and Adolescents: 4 to 10 mg/kg/day in divided doses 3 to 4 times daily; maximum daily dose: 300 mg/day (Ref).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricAllopurinol and oxypurinol are dialyzable.Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, the following guidelines have been used by some clinicians:Management of hyperuricemia associated with chemotherapy: Oral, IV:Aronoff 2007:GFR 30 to 50 mL/minute/1.73 m2: Administer 50% of normal dose.GFR 10 to 29 mL/minute/1.73 m2: Administer 50% of normal dose.GFR <10 mL/minute/1.73 m2: Administer 30% of normal dose.Intermittent hemodialysis: Administer 30% of normal dose.Peritoneal dialysis: Administer 30% of normal dose.Continuous renal replacement therapy (CRRT): Administer 50% of normal dose.Coiffier 2008: Dosage reduction of 50% is recommended in renal impairment.Dosing: Hepatic Impairment: PediatricThere are no dosage adjustments provided in the manufacturer's labeling.Dosing: Older AdultRefer to adult dosing.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution Reconstituted, Intravenous, as sodium [strength expressed as base]: Generic: 500 mg (1 ea)Solution Reconstituted, Intravenous, as sodium [strength expressed as base, preservative free]: Aloprim: 500 mg (1 ea)Generic: 500 mg (1 ea)Tablet, Oral: Zyloprim: 100 mg [scored]Zyloprim: 300 mg [scored; contains corn starch, fd&c yellow #6(sunset yellow)alumin lake]Generic: 100 mg, 200 mg, 300 mgGeneric Equivalent Available: USYesDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Tablet, Oral: Zyloprim: 100 mg, 200 mg, 300 mgGeneric: 100 mg, 200 mg, 300 mgAdministration: AdultOral: Administer after meals.IV: The rate of infusion depends on the volume of the infusion. IV daily dose can be administered as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals (Ref).Tumor lysis syndrome prevention: Administer aggressive fluids sufficient to maintain adequate hydration and urinary output; whenever possible, allopurinol therapy should be initiated 24 to 48 hours before the start of chemotherapy (and other treatments) known to cause tumor lysis (Ref).Other indications: Administer fluids sufficient to yield daily urinary output of at least 2 L and to maintain a neutral or, preferably, slightly alkaline urine.Administration: PediatricNote: Fluid intake should be sufficient to yield neutral or slightly alkaline (preferably) urine and a daily urine output of at least 2 L in adults.Oral: Administer after meals with plenty of fluidParenteral: The rate of infusion is dependent upon the volume of the infusion; infuse maximum single daily doses (600 mg/day) over ≥30 minutes; whenever possible, therapy should be initiated at 12 to 24 hours (pediatric patients) or 24 to 48 hours (adults) before the start of chemotherapy known to cause tumor lysis (including adrenocorticosteroids) (Ref). Intravenous daily therapy can be administered as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals.Use: Labeled IndicationsOral:Gout, treatment: Management of primary or secondary gout (acute attack, tophi, joint destruction, uric acid lithiasis, and/or nephropathy)Guideline recommendations: EULAR guidelines: Urate-lowering therapy (ULT) (eg, allopurinol) is indicated in all patients with recurrent flares, tophi, urate arthropathy, and/or renal stones. ULT initiation is recommended close in time to first diagnosis in patients presenting at a young age (<40 years of age) or with very high serum uric acid levels (>8 mg/dL) and/or comorbidities (eg, renal impairment, hypertension, ischemic heart disease, heart failure) (EULAR [Richette 2017]).Nephrolithiasis, prevention of recurrent calcium stones: Management in patients with hyperuricosuria (uric acid excretion >800 mg/day in men and >750 mg/day in women)Tumor lysis syndrome, prevention: Management of hyperuricemia associated with cancer treatment for leukemia, lymphoma, and other malignanciesLimitations of use: Allopurinol is not recommended for the treatment of asymptomatic hyperuricemia. Allopurinol reduces serum and urinary uric acid concentrations; its use should be individualized for each patient and requires an understanding of its mode of action and pharmaco*kinetics.IV: Tumor lysis syndrome, prevention: Management of hyperuricemia associated with cancer treatment for leukemia, lymphoma, or solid tumor malignancies in pediatric and adult patients who cannot tolerate oral therapy.Use: Off-Label: AdultNephrolithiasis, prevention of recurrent uric acid stonesMedication Safety IssuesSound-alike/look-alike issues: Allopurinol may be confused with Apresoline Zyloprim may be confused with zolpidem, ZORprin, ZoviraxAdverse Reactions (Significant): ConsiderationsAcute gout attacksAcute gout attacks have been reported during the early stages of allopurinol administration even when normal or optimal serum uric acid levels have been attained. Gout attacks generally decrease in duration and severity after several months of urate-lowering therapy (Ref).Mechanism: Dose-related; related to the pharmacologic action. Decrease in serum urate leads to the dissolution of monosodium urate crystal deposits and dispersion of crystals, causing gout flares (Ref).Onset: Varied; most likely to occur within first 6 months of treatment (Ref); risk is lower after 1 year of treatment (Ref).Risk factors:• Early in course of treatment (Ref)• Initiating urate-lowering treatment without concurrent gout flare prophylaxis (Ref)• Withdrawal of anti-inflammatory gout flare prophylaxis (Ref)• Uric acid >6 mg/dL during treatment (Ref)• Rapid decreases and/or greater reduction in uric acid (Ref)• Persistence of tophi (Ref)HepatotoxicityMost cases of acute hepatotoxicity with allopurinol are associated with drug reaction with eosinophilia and systemic symptoms (DRESS) and allopurinol hypersensitivity syndrome (Ref). May rarely occur without any features of DRESS (Ref). The pattern of liver enzyme elevations is usually hepatocellular or mixed, but can be cholestatic (Ref).Mechanism: Non-dose-related; immunologic. DRESS syndrome is T-cell-mediated (Ref).Onset: Varied; usually occur 1 to 5 weeks after initiation (Ref).Risk factors:• African-American race (Ref)• Preexisting kidney disease (Ref)Hypersensitivity reactions (delayed)Allopurinol is associated with a variety of delayed hypersensitivity reactions (often termed allopurinol hypersensitivity syndrome [AHS]), ranging from mild maculopapular rash to severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) (Ref).Mechanism: Non-dose-related; immunologic. Delayed hypersensitivity reactions, including maculopapular eruptions and SCARs are T-cell-mediated (Ref).Onset: Delayed hypersensitivity reactions: varied; usually occur 3 to 9 weeks after initiation (Ref), but may occur more rapidly (usually within 1 to 4 days) upon reexposure (Ref).Risk factors:• Presence of HLA-B*5801 allele is strongly associated with SCARs, especially with concomitant kidney impairment and in some Asian populations (Ref). HLA-A*3303 and HLA-C*0302 alleles are associated with SJS or TEN, especially in Asian populations (Ref)• Dose (Ref)• Kidney impairment: Correlated to delayed clearance of oxypurinol (metabolite of allopurinol) and potentially high levels of granulysin (Ref)• Older adults (≥60 years of age), possibly due to kidney impairment (Ref)• Females (Ref)• Asymptomatic hyperuricemia, especially in patients with concomitant kidney or cardiovascular disease (Ref)• Concomitant cardiovascular disease (Ref)• Concomitant diuretic use: Although diuretic use has been associated with increased risk of allopurinol hypersensitivity reactions (Ref), some studies have not found an association between diuretic use and AHS (Ref)• Cross-reactivity between allopurinol and febuxostat: Although there may be an increased risk of a skin reaction with febuxostat in patients with a history of reactions to allopurinol, whether this represents 2 separate reactions or cross-reactivity is not known (Ref)Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.1% to 10%:Dermatologic: Maculopapular rash (≤3%; pruritic), skin rash (≤2%)Gastrointestinal: Nausea (1%), vomiting (≤1%)Neuromuscular & skeletal: Gout (≤6%; acute)Renal: Renal failure syndrome (≤1%)<1%:Cardiovascular: Bradycardia, edema, flushing, heart failure, hypertension, hypotension, low cardiac output, necrotizing angiitis, pericarditis, peripheral vascular disease, pulmonary embolism, septic shock, thrombophlebitis, vasculitis, vasodilation, ventricular fibrillationDermatologic: Alopecia, cellulitis, diaphoresis, ecchymoses, eczema, exfoliative dermatitis, furunculosis, lichen planus, onycholysis, purpuric rash, skin edema, Stevens-Johnson syndrome (Gupta 2019), toxic epidermal necrolysis (Hoyer 2021), urticaria, vesicobullous dermatitisEndocrine & metabolic: Albuminuria, decreased libido, gynecomastia, hypercalcemia, hyperglycemia, hyperkalemia, hyperlipidemia, hypernatremia, hyperphosphatemia, hyperuricemia, hypervolemia, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, lactic acidosis, metabolic acidosis, water intoxicationGastrointestinal: Abdominal pain, ageusia, anorexia, constipation, dysgeusia, dyspepsia, enlargement of abdomen, enlargement of salivary glands, flatulence, gastritis, gastrointestinal hemorrhage, hemorrhagic pancreatitis, intestinal obstruction, proctitis, stomatitisGenitourinary: Glycosuria, hematuria, impotence, male infertility, oliguria, uremia, urinary tract infectionHematologic & oncologic: Agranulocytosis, anemia, aplastic anemia, bone marrow aplasia, bone marrow depression, chronic myelocytic leukemia, disseminated intravascular coagulation, eosinophilia, eosinophilic fibrohistiocytic bone marrow lesion, hemolytic anemia, hemorrhage, hypoprothrombinemia, leukocytosis, leukopenia, lymphadenopathy, lymphocytosis, neutropenia, pancytopenia, reticulocytosis, splenomegaly, thrombocytopenia, tumor lysis syndromeHepatic: Cholestatic jaundice, granulomatous hepatitis, hepatic failure, hepatic necrosis, hepatomegaly (Childs 2012), hepatotoxicity (Chalasani 2021), hyperbilirubinemia, jaundiceHypersensitivity: Drug reaction with eosinophilia and systemic symptoms (Chung 2015), facial edema, hypersensitivity angiitis, tongue edemaInfection: Infection, sepsisLocal: Injection-site reactionNervous system: Agitation, amnesia, asthenia, cerebral infarction, cerebrovascular accident, chills, coma, confusion, depression, dizziness, drowsiness, dystonia, headache, hypotonia, insomnia, malaise, mental status changes, myoclonus, neuritis, pain, paralysis, paresthesia, peripheral neuropathy, seizure, status epilepticus, tremor, twitching, vertigoNeuromuscular & skeletal: Arthralgia, foot-drop, myalgia, myopathyOphthalmic: Amblyopia, cataract, conjunctivitis, iritis, macular retinitis, optic neuritisOtic: TinnitusRenal: Nephritis (including interstitial nephritis) (Gelbart 1977)Respiratory: Acute respiratory distress syndrome, apnea, asthma, bronchospasm, epistaxis, pharyngitis, respiratory failure, rhinitis, tachypneaMiscellaneous: FeverFrequency not defined:Gastrointestinal: DiarrheaHepatic: Increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferasePostmarketing:Dermatologic: Sweet syndrome (Polimeni 2016)Hematologic & oncologic: Pure red cell aplasia (Shankar 2003)Hypersensitivity: Hypersensitivity reaction (allopurinol hypersensitivity syndrome; can be severe hypersensitivity reaction) (Chen 2005)ContraindicationsSevere hypersensitivity reaction to allopurinol or any component of the formulation.Canadian labeling: Additional contraindications (not in the US labeling): Breastfeeding mothers and children (except those with cancer therapy-induced hyperuricemia or Lesch-Nyhan syndrome).Note: To avoid the risk of severe cutaneous adverse reactions (SCAR), HLA-B*5801-positive patients should avoid allopurinol (Perez-Ruiz 2022; Saito 2016). The American College of Rheumatology recommends HLA-B*5801 screening in patients at elevated risk of SCAR, including patients of Asian descent (eg, Korean, Han Chinese, Thai) and African American patients (ACR [FitzGerald 2020]).Warnings/PrecautionsConcerns related to adverse effects:• CNS effects: May occasionally cause drowsiness; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).Disease-related concerns:• Renal impairment: Dose reductions are recommended in patients with renal impairment; monitor closely. Some patients with preexisting renal disease or poor urate clearance have shown a rise in BUN with allopurinol. Patients with renal impairment should be carefully monitored during the early stages of allopurinol treatment; reduce the dose or withdraw therapy if increased renal function abnormalities appear and persist. Renal failure associated with allopurinol has been observed in patients with hyperuricemia secondary to neoplastic diseases. Concurrent conditions including multiple myeloma and congestive myocardial disease were present among patients whose renal dysfunction increased after allopurinol was begun. Renal failure is also frequently associated with gouty nephropathy. Albuminuria has been observed among patients who developed clinical gout following chronic glomerulonephritis and chronic pyelonephritis.Other warnings/precautions:• Hydration: For tumor lysis syndrome prevention, administer aggressive fluids sufficient to maintain adequate hydration and urinary output (Coiffier 2008). For other indications, fluid intake sufficient to yield a daily urinary output of at least 2 L and maintenance of a neutral or (preferably) a slightly alkaline urine are desirable in order to avoid possible formation of xanthine calculi due to allopurinol therapy and to help prevent renal urate precipitation in patients receiving concomitant uricosuric agents.Metabolism/Transport EffectsNone known.Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Aluminum Hydroxide: May decrease the serum concentration of Allopurinol. Management: Consider administering allopurinol 3 hours prior to aluminum hydroxide. Risk D: Consider therapy modificationAmoxicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Amoxicillin.Risk C: Monitor therapyAmpicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Ampicillin.Risk C: Monitor therapyAngiotensin-Converting Enzyme Inhibitors: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk C: Monitor therapyAzaTHIOprine: Allopurinol may increase serum concentrations of the active metabolite(s) of AzaTHIOprine. More specifically, allopurinol may increase mercaptopurine serum concentrations and promote formation of active thioguanine nucleotides.Management: Reduce azathioprine dose to one third to one quarter of the usual dose if used with allopurinol, and monitor closely for systemic toxicity. Further dose reduction or alternative therapies should be considered for patients with low or absent TPMT activity. Risk D: Consider therapy modificationBacampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Bacampicillin.Risk C: Monitor therapyBendamustine: Allopurinol may enhance the adverse/toxic effect of Bendamustine. Specifically, the risk of severe skin reactions may be enhanced.Risk C: Monitor therapyCarBAMazepine: Allopurinol may increase the serum concentration of CarBAMazepine.Risk C: Monitor therapyCyclophosphamide: Allopurinol may increase the serum concentration of Cyclophosphamide.Risk C: Monitor therapyCycloSPORINE (Systemic): Allopurinol may increase the serum concentration of CycloSPORINE (Systemic).Risk C: Monitor therapyDidanosine: Allopurinol may increase the serum concentration of Didanosine.Risk X: Avoid combinationDoxofylline: Allopurinol may increase the serum concentration of Doxofylline.Risk C: Monitor therapyFluorouracil Products: Allopurinol may decrease serum concentrations of the active metabolite(s) of Fluorouracil Products.Risk X: Avoid combinationLoop Diuretics: May enhance the adverse/toxic effect of Allopurinol. Loop Diuretics may increase the serum concentration of Allopurinol. Specifically, Loop Diuretics may increase the concentration of Oxypurinol, an active metabolite of Allopurinol. Risk C: Monitor therapyMercaptopurine: Allopurinol may increase the serum concentration of Mercaptopurine. Allopurinol may also promote formation of active thioguanine nucleotides.Management: Reduce the mercaptopurine dose to one third to one quarter of the usual dose if used with allopurinol, and monitor closely for systemic toxicity. Risk D: Consider therapy modificationPegloticase: Allopurinol may enhance the adverse/toxic effect of Pegloticase. Specifically, Allopurinol may blunt increases in serum urate that would signal an increased risk of anaphylaxis and infusion reactions.Risk X: Avoid combinationRiluzole: Allopurinol may enhance the adverse/toxic effect of Riluzole. Specifically, the risk of hepatotoxicity may be increased.Management: Consider alternatives to allopurinol in patients receiving treatment with riluzole due to the potential for additive hepatotoxicity. Risk D: Consider therapy modificationTheophylline Derivatives: Allopurinol may increase the serum concentration of Theophylline Derivatives.Risk C: Monitor therapyThiazide and Thiazide-Like Diuretics: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk C: Monitor therapyVitamin K Antagonists (eg, warfarin): Allopurinol may enhance the anticoagulant effect of Vitamin K Antagonists.Management: Monitor for increased prothrombin times (PT)/therapeutic effects of oral anticoagulants if allopurinol is initiated/dose increased, or decreased effects if allopurinol is discontinued/dose decreased. Reductions in coumarin dosage will likely be needed. Risk D: Consider therapy modificationPregnancy ConsiderationsAllopurinol crosses the placenta.Following a single dose of allopurinol 500 mg IV immediately prior to delivery, allopurinol and the oxypurinol metabolite were present in cord blood (Kaandorp 2014; Torrance 2009).Outcome data following maternal use of allopurinol in pregnancy are limited. Based on similar adverse outcomes from 2 case reports, use during the first trimester is generally avoided until additional data are available. Close maternal and fetal monitoring is recommended when treatment with allopurinol is needed (El-Sonbaty 2001; Hoeltzenbein 2013; Jones 2021; Laube 2021; Patel 2022; Serikawa 2011; Sheikh 2015; Simsek 2018; van Veen 2015).Breastfeeding ConsiderationsAllopurinol and the oxypurinol metabolite are present in breast milk.Data related to the presence of allopurinol in breast milk are available from a single case report. Allopurinol 300 mg/day was initiated 1 week postpartum to a patient for the treatment of recurrent pyelonephritis. After 4 weeks of treatment, breast milk, maternal blood, and infant blood were sampled. Allopurinol concentrations in breast milk were 0.9 mcg/mL (2 hours) and 1.4 mcg/mL (4 hours) after the dose. Oxypurinol breast milk concentrations were 53.7 mcg/mL (2 hours) and 48 mcg/mL (4 hours) after the dose. Four hours after the dose, plasma concentrations of allopurinol were 1 mcg/mL (mother) and below the limit of detection in the breastfed infant; oxypurinol concentrations were 19.9 mcg/mL (mother) and 6.6 mcg/mL (infant). Authors of the study calculated the estimated daily infant dose via breast milk to be 0.14 to 0.2 mg/kg/day (allopurinol) and 7.2 to 8 mg/kg/day (oxypurinol). Adverse events were not reported in the infant (Kamilli 1993).Due to the potential for adverse events, breastfeeding is not recommended by the manufacturer during treatment and for 1 week after the last allopurinol dose. Other sources consider allopurinol compatible or likely to have low risk with breastfeeding (Laube 2021; WHO 2002). However close monitoring for adverse events, such as hypersensitivity reactions and cytopenia, in the breastfed infant is recommended (Patel 2022).Dietary ConsiderationsFor tumor lysis syndrome prevention, administer aggressive fluids sufficient to maintain adequate hydration and urinary output (Coiffier 2008). For other indications, fluid intake should be administered to yield neutral or slightly alkaline urine and an output of ~2 L (in adults).Monitoring ParametersCBC; serum uric acid levels at least 2 to 4 weeks after every dose titration until desired level is achieved, then every 6 months (symptomatic patients) or every 12 months (all patients on urate-lowering therapy, regardless of symptoms) (FitzGerald 2018; Perez-Ruiz 2022), LFTs (periodically in patients with preexisting hepatic disease), renal function (BUN, serum creatinine, or creatinine clearance [prior to initiation and periodically]), prothrombin time (periodically in patients receiving warfarin). Monitor hydration status, signs/symptoms of hepatotoxicity (if occurs, evaluate LFTs), and signs/symptoms of hypersensitivity reactions, including severe cutaneous adverse reactions (SCAR). Consider HLA-B*5801 testing prior to initiation of therapy in patients at elevated risk for SCAR (eg, patients of Southeast Asian descent [eg, Korean, Han Chinese, Thai], African American patients).Reference RangeUric acid, serum:Children and Adolescents:Uric Acid Normal ValuesAgeNormal Serum Concentration1 to 3 years1.8 to 5 mg/dL4 to 6 years2.2 to 4.7 mg/dL7 to 9 years2 to 5 mg/dL10 to 11 years: Male2.3 to 5.4 mg/dL10 to 11 years: Female3 to 4.7 mg/dL12 to 13 years: Male2.7 to 6.7 mg/dL14 to 15 years: Male2.4 to 7.8 mg/dL12 to 15 years: Female3 to 5.8 mg/dL16 to 19 years: Male4 to 8.6 mg/dL16 to 19 years: Female3 to 5.9 mg/dLAdults:Normal values:Males: 3.4 to 7 mg/dL or slightly moreFemales: 2.4 to 6 mg/dL or slightly moreGoal during therapy for gout: <6 mg/dL; <5 mg/dL in patients with severe gout (eg, tophi, frequent attacks, chronic arthropathy) (EULAR [Richette 2017]). Levels <3 mg/dL are not recommended long-term (EULAR [Richette 2017]).Note: Serum uric acid values >7 mg/dL do not necessarily represent clinical gout; the American College of Rheumatology clinical practice guidelines recommend against initiating pharmacologic management of asymptomatic hyperuricemia (ACR [FitzGerald 2020]).Mechanism of ActionAllopurinol inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine to uric acid. Allopurinol is metabolized to oxypurinol which is also an inhibitor of xanthine oxidase; allopurinol acts on purine catabolism, reducing the production of uric acid without disrupting the biosynthesis of vital purines.Pharmaco*kineticsOnset of action:Gout: Decrease in serum and urine uric acid: 2 to 3 days; peak effect: 1 week or longer; normal serum urate levels achieved typically within 1 to 3 weeks.Cancer therapy-induced hyperuricemia: Median time to plasma uric acid control: 27 hours (Cortes 2010).Absorption: Oral: 90% from GI tract.Distribution: Vss: ~0.87 ± 0.13 L/kg.Metabolism: Rapidly oxidized to active metabolites, primarily oxypurinol.Bioavailability: ~49% to 53%.Half-life elimination:Oral: Parent drug: ~1 to 2 hours; Oxypurinol: ~15 hours.IV: Parent drug: 1.21 ± 0.33 hours; Oxypurinol: 23.5 ± 4.5 hours.Time to peak, plasma: Oral: Allopurinol: 1.5 hours; Oxypurinol: 4.5 hours.Excretion: Urine (76% as oxypurinol, 12% as unchanged drug); feces (~20%).Pricing: USSolution (reconstituted) (Allopurinol Sodium Intravenous)500 mg (per each): $3,480.00 - $4,680.00Solution (reconstituted) (Aloprim Intravenous)500 mg (per each): $4,784.47Tablets (Allopurinol Oral)100 mg (per each): $0.24 - $0.48200 mg (per each): $7.95300 mg (per each): $0.61 - $0.92Tablets (Zyloprim Oral)100 mg (per each): $3.98300 mg (per each): $11.19Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalAcepurin (NL);Adenock (JP);AL (PH);Alinol (TH);Allnol (HK);Allo (CO);Allo-Puren (DE);Allogut (TR);Allonol (LK);Allopin (TH);Allopur (CH, NO);Allopurinol-ratiopharm (LU);Alloric (TH);Alloril (IL);Allosig (AU);Allozym (JP);Allpargin (LU);Allurase (PH);Alluric (EG);Allurit (IT);Alopron (BM, BS, GY, JM, MT, SR, TR, TT);Alopur (IE);Alopurinol (HR);Aloric (BD);Alorinol (EG);Alositol (JP);Alpurase (PH);Alpuric (LU);Alpurin (PH);Alunlan (TW);Aluric (LB);Aluron (VE);Anoprolin (JP);Anzief (JP);Ao Mai Bi Li (CN);Aprinol (JP);Apronal (TH);Apurin (FI, GR);Apurol (SA);Atisuril (CR, DO, GT, HN, MX, NI, PA, SV);Aurinol (PH);Benoxuric (ID);Bleminal (DE);Caplenal (GB);Cellidrin (DE);Clint (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW);Dertrifort (CR, DO, GT, HN, NI, PA, SV);Etindrax (MX);Foligan (DE);Genozyl (MX);Gichtex (AT);Goutex (BD);Goutilex (TW);Hamarin (GB);Huma-Purol (HU);Isoric (ID);Ketanrift (JP);Ketobun-A (JP);Lessuric (EG);Litinol (VE);Llanol (VN);Logout (LK);Loric (SA);Loric-100 (BH, PH, QA);Loric-300 (BH, PH);Masaton (JP);Mensil (PY);Mephanol (AE, BF, BJ, CH, CI, CY, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZM, ZW);Milurit (BG, CZ, HU, SK);Miniplanor (JP);Neufan (JP);Nilapur (ID);Nipurol (VE);No-Uric (AE, BH, CY, ET, IQ, IR, JO, KW, LB, LY, OM, QA, SY, YE);Pritanol (ID);Progout (AU, SG);Puribel 300 (MX);Puricemia (ID);Puricos (ZA);Purinol (AE, BD, CZ, IE, JO, MY, QA, RU, SA, ZW);Remid (DE, PY);Riball (JP);Ridonra (TW);Rinolic (ID);Ripunin (TW);Sadapron (VN);Salterprim (ZA);Sinoric (ID);Takanarumin (JP);Tipuric (IE);Tonsaric (TW);Trianol (PH);Tylonic (ID);Unizuric (CR, DO, GT, HN, NI, PA, SV);Unizuric 300 (MX);Uranid (TW);Uric (JP);Uricad (TH);Uriconorm (CH);Urinol (MY);Urocuad (CO);Urogquad (AR);Uroquad (AE, BF, BJ, BM, BS, CI, ET, GH, GM, GN, GY, JM, KE, LR, MA, ML, MR, MU, MW, NE, NG, SA, SC, SD, SL, SN, SR, TN, TT, TZ, UG, ZM, ZW);Urosin (AT, DE, EC, LU);Valeric (CN);Xandase (TH);Xanol (TH);Xanurace (PH);Xoric (BD);Xylonol (TW);Yi Da Tong (CN);Zanuric (JO);Zylapour (GR);Zyloprim (AU, BB, BM, BS, CR, DO, GT, GY, HN, JM, MX, NI, PA, PH, PR, PY, SR, SV, TT);Zyloric (AE, BE, BF, BH, BJ, BR, CH, CI, CL, CY, DE, EE, EG, ES, ET, FI, FR, GB, GH, GM, GN, HK, ID, IE, IN, IQ, IR, IT, JO, KE, KR, KW, LB, LR, LU, LY, MA, ML, MR, MT, MU, MW, MY, NE, NG, NL, NO, OM, PK, PL, PT, QA, RU, SA, SC, SD, SE, SG, SK, SL, SN, SY, TH, TN, TR, TZ, UG, UY, VE, VN, YE, ZM, ZW);Zyngot (PE);Zyroric (KR)For country code abbreviations (show table)Adler NR, Aung AK, Ergen EN, Trubiano J, Goh MSY, Phillips EJ. Recent advances in the understanding of severe cutaneous adverse reactions. Br J Dermatol. 2017;177(5):1234-1247. doi:10.1111/bjd.15423 [PubMed 28256714]Al-Kawas FH, Seeff LB, Berendson RA, Zimmerman HJ, Ishak KG. Allopurinol hepatotoxicity. Report of two cases and review of the literature. Ann Intern Med. 1981;95(5):588-590. doi:10.7326/0003-4819-95-5-588 [PubMed 7294548]Allen LV, Erickson MA 3rd. Stability of Acetazolamide, Allopurinol, Azathioprine, Clonazepam, and Flucytosine in Extemporaneously Compounded Oral Liquids. Am J Health Syst Pharm. 1996;53(16):1944-1949. [PubMed 8862208]Allopurinol. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; February 24, 2015. [PubMed 31643428]Allopurinol tablet [prescribing information]. Morgantown, WV: Mylan Pharmaceuticals Inc; June 2015Aloprim (allopurinol) injection [prescribing information]. Morgantown, WV: Mylan Institutional LLC; February 2022.Appelbaum SJ, Mayersohn M, Dorr RT, et al. Allopurinol kinetics and bioavailability. Intravenous, oral and rectal administration. Cancer Chemother Pharmacol. 1982;8(1):93-98. [PubMed 7094203]Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th ed. American College of Physicians; 2007.Bardin T, Chalès G, Pascart T, et al. Risk of cutaneous adverse events with febuxostat treatment in patients with skin reaction to allopurinol. A retrospective, hospital-based study of 101 patients with consecutive allopurinol and febuxostat treatment. Joint Bone Spine. 2016;83(3):314-317. doi:10.1016/j.jbspin.2015.07.011 [PubMed 26709250]Becker MA, MacDonald PA, Hunt BJ, Lademacher C, Joseph-Ridge N. Determinants of the clinical outcomes of gout during the first year of urate-lowering therapy. Nucleosides Nucleotides Nucleic Acids. 2008;27(6):585-591. doi:10.1080/15257770802136032 [PubMed 18600509]Becker MA, Schumacher HR Jr, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005;353(23):2450-2461. doi:10.1056/NEJMoa050373 [PubMed 16339094]Blumenthal KG, Peter JG, Trubiano JA, Phillips EJ. Antibiotic allergy. Lancet. 2019;393(10167):183-198. doi:10.1016/S0140-6736(18)32218-9 [PubMed 30558872]Borstad GC, Bryant LR, Abel MP, Scroggie DA, Harris MD, Alloway JA. Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis. J Rheumatol. 2004;31(12):2429-2432. [PubMed 15570646]Brockow K, Przybilla B, Aberer W, et al. Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM). Allergo J Int. 2015;24(3):94-105. doi:10.1007/s40629-015-0052-6 [PubMed 26120552]Chalasani NP, Hayashi PH, Bonkovsky HL, et al. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2014;109(7):950-966. [PubMed 24935270]Chalasani NP, Maddur H, Russo MW, Wong RJ, Reddy KR; Practice parameters Committee of the American College of Gastroenterology. ACG clinical guideline: diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2021;116(5):878-898. doi:10.14309/ajg.0000000000001259 [PubMed 33929376]Chawla SK, Patel HD, Parrino GR, Soterakis J, Lopresti PA, D'Angelo WA. Allopurinol hepatotoxicity. Case report and literature review. Arthritis Rheum. 1977;20(8):1546-1549. doi:10.1002/art.1780200817 [PubMed 921828]Chen IH, Kuo MC, Hwang SJ, Chang JM, Chen HC. Allopurinol-induced severe hypersensitivity with acute renal failure. Kaohsiung J Med Sci. 2005;21(5):228-232. doi: 10.1016/S1607-551X(09)70192-5 [PubMed 15960069]Chen YC, Chiu HC, Chu CY. Drug reaction with eosinophilia and systemic symptoms: a retrospective study of 60 cases. Arch Dermatol. 2010;146(12):1373-1379. doi:10.1001/archdermatol.2010.198 [PubMed 20713773]Childs L, Dow C. Allopurinol-induced hepatomegaly. BMJ Case Rep. 2012;bcr2012007283. doi:10.1136/bcr-2012-007283 [PubMed 23087287]Choi HG, Byun J, Moon CH, et al. Allopurinol-induced DRESS syndrome mimicking biliary obstruction. Clin Mol Hepatol. 2014;20(1):71-75. doi:10.3350/cmh.2014.20.1.71 [PubMed 24757661]Chung WH, Chang WC, Stocker SL, et al. Insights into the poor prognosis of allopurinol-induced severe cutaneous adverse reactions: the impact of renal insufficiency, high plasma levels of oxypurinol and granulysin. Ann Rheum Dis. 2015;74(12):2157-2164. doi:10.1136/annrheumdis-2014-205577 [PubMed 25115449]Coiffier B, Altman A, Pui CH, Younes A, Cairo MS. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol 2008;26(16):2767-2778. [PubMed 18509186]Copelovitch L. Urolithiasis in children: medical approach. Pediatr Clin North Am. 2012;59(4):881-896. [PubMed 22857835]Cortes J, Moore JO, Maziarz RT, et al. Control of plasma uria acid in adults at risk for tumor lysis syndrome: efficacy and safety of rasburicase alone and rasburicase followed by allopurinol compared with allopurinol alone-results of a multicenter phase III study. J Clin Oncol. 2010;28(27):4207-4213. [PubMed 20713865]Curhan GC. Kidney stones in adults: Prevention of recurrent kidney stones. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 2, 2021.Curhan GC. Uric acid nephrolithiasis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 21, 2018.Currie WJ, Turmer P, Young JH. Evaluation of once a day allopurinol administration in man. Br J Clin Pharmacol. 1978;5(1):90-91. [PubMed 619943]Dalbeth N, Stamp L. Allopurinol dosing in renal impairment: walking the tightrope between adequate urate lowering and adverse events. Semin Dial. 2007;20(5):391-395. [PubMed 17897242]Day RO, Kannangara DR, Hayes JM, Furlong TJ. Successful use of allopurinol in a patient on dialysis. BMJ Case Rep. 2012;2012:bcr0220125814. doi:10.1136/bcr.02.2012.5814 [PubMed 22675142]Day RO, Kannangara DR, Stocker SL, Carland JE, Williams KM, Graham GG. Allopurinol: insights from studies of dose-response relationships. Expert Opin Drug Metab Toxicol. 2017;13(4):449-462. doi:10.1080/17425255.2017.1269745 [PubMed 27927043]El-Sonbaty MR, Bitar Z, Abdulrazak A. Acute spontaneous tumor-lysis syndrome in a pregnant woman with non-Hodgkin's lymphoma. Int J Hematol. 2001;73(3):386-389. doi:10.1007/BF02981967 [PubMed 11345208]Ettinger B, Tang A, Citron JT, Livermore B, Williams T. Randomized trial of allopurinol in the prevention of calcium oxalate calculi. N Engl J Med. 1986;315(22):1386-1389. doi: 10.1056/NEJM198611273152204. [PubMed 3534570]FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology guideline for the management of gout. Arthritis Care Res (Hoboken). 2020;72(6):744-760. doi:10.1002/acr.24180 [PubMed 32391934]FitzGerald JD, Mikuls TR, Neogi T, et al. Development of the American College of Rheumatology electronic clinical quality measures for gout. Arthritis Care Res (Hoboken). 2018;70(5):659-671. doi:10.1002/acr.23500 [PubMed 29649348]Gahart BL, Nazareno AR. 2012 Intravenous Medications: A Handbook for Nurses and Health Professionals. 28th ed. Elsevier/Mosby; 2012:58-59.Gelbart DR, Weinstein AB, Fajardo LF. Allopurinol-induced interstitial nephritis. Ann Intern Med. 1977;86(2):196-198. doi:10.7326/0003-4819-86-2-196 [PubMed 835946]Gupta SS, Sabharwal N, Patti R, Kupfer Y. Allopurinol-induced Stevens-Johnson syndrome. Am J Med Sci. 2019;357(4):348-351. doi:10.1016/j.amjms.2018.11.018 [PubMed 30638600]Hande KR, Noone RM, Stone WJ. Severe allopurinol toxicity. Description and guidelines for prevention in patients with renal insufficiency. Am J Med. 1984;76(1):47-56. doi:10.1016/0002-9343(84)90743-5 [PubMed 6691361]Hayes CP Jr, Metz EN, Robinson RR, Rundles RW. The use of allopurinol (HPP) to control hyperuricemia in patients on chronic intermittent hemodialysis. Trans Am Soc Artif Intern Organs. 1965;11:247-254. doi 10.1097/00002480-196504000-00047 [PubMed 14329092]Heilberg IP. Treatment of patients with uric acid stones. Urolithiasis. 2016;44(1):57-63. doi:10.1007/s00240-015-0843-8 [PubMed 26645868]Hershfield MS, Callaghan JT, Tassaneeyakul W, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing. Clin Pharmacol Ther. 2013;93(2):153-158. [PubMed 23232549]Hoeltzenbein M, Stieler K, Panse M, Wacker E, Schaefer C. Allopurinol Use during Pregnancy - Outcome of 31 Prospectively Ascertained Cases and a Phenotype Possibly Indicative for Teratogenicity. PLoS One. 2013;8(6):e66637. doi:10.1371/journal.pone.0066637 [PubMed 23840514]Hoyer D, Atti C, Nuding S, Vogt A, Sedding DG, Schott A. Toxic epidermal necrolysis caused by allopurinol: a serious but still underestimated adverse reaction. Am J Case Rep. 2021;22:e932921. doi:10.12659/AJCR.932921 [PubMed 34634004]Imai H, Kamei H, Onishi Y, et al. Successful living-donor liver transplantation for cholestatic liver failure induced by allopurinol: case report. Transplant Proc. 2015;47(9):2778-2781. doi:10.1016/j.transproceed.2015.09.038 [PubMed 26680093]Jennings CG, Mackenzie IS, Flynn R, et al; FAST study group. Up-titration of allopurinol in patients with gout. Semin Arthritis Rheum. 2014;44(1):25-30. doi:10.1016/j.semarthrit.2014.01.004 [PubMed 24560169]Jones AM, Tower C, Green D, Stepien KM. Multidisciplinary management of pregnancy and labour in a patient with glycogen storage disease type 1a. BMJ Case Rep. 2021;14(8):e241161. doi:10.1136/bcr-2020-241161 [PubMed 34380672]Kaandorp JJ, van den Broek MP, Benders MJ, et al; ALLO-trial Study Group. Rapid target allopurinol concentrations in the hypoxic fetus after maternal administration during labour. Arch Dis Child Fetal Neonatal Ed. 2014;99(2):F144-F148. doi:10.1136/archdischild-2013-304876 [PubMed 24352085]Kamilli I, Gresser U. Allopurinol and oxypurinol in human breast milk. Clin Investig. 1993;71(2):161-164. doi:10.1007/BF00179999 [PubMed 8461629]Keller SF, Lu N, Blumenthal KG, et al. Racial/ethnic variation and risk factors for allopurinol-associated severe cutaneous adverse reactions: a cohort study. Ann Rheum Dis. 2018;77(8):1187-1193. doi:10.1136/annrheumdis-2017-212905 [PubMed 29653927]Kenny JE, Goldfarb DS. Update on the pathophysiology and management of uric acid renal stones. Curr Rheumatol Rep. 2010;12(2):125-129. doi:10.1007/s11926-010-0089-y [PubMed 20425021]Khanna D, Fitzgerald JD, Khanna PP, et al; American College of Rheumatology. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012;64(10):1431-1446. [PubMed 23024028]Kliegman RM, Stanton BF, St. Gemell JW, et al, eds. Nelson Textbook of Pediatrics. 19th ed. Saunders Elsevier; 2011.Larson RA, Pui CH. Tumor lysis syndrome: Prevention and treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 10, 2019.Latourte A, Bardin T, Richette P. Prophylaxis for acute gout flares after initiation of urate-lowering therapy. Rheumatology (Oxford). 2014;53(11):1920-1926. doi:10.1093/rheumatology/keu157 [PubMed 24758886]Laube R, Paramsothy S, Leong RW. Review of pregnancy in Crohn's disease and ulcerative colitis. Therap Adv Gastroenterol. 2021;14:17562848211016242. doi:10.1177/17562848211016242 [PubMed 34046084]Li X, Zhao Z, Sun SS. Association of human leukocyte antigen variants and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: a meta-analysis. Am J Health Syst Pharm. 2017;74(9):e183-e192. doi:10.2146/ajhp160243 [PubMed 28438823]Lien YH, Logan JL. Cross-reactions between allopurinol and febuxostat. Am J Med. 2017;130(2):e67-e68. doi:10.1016/j.amjmed.2016.08.042 [PubMed 27667702]Lipkin ME, Preminger GM. Demystifying the medical management of nephrolithiasis. Rev Urol. 2011;13(1):34-38. [PubMed 21826126]Mitra S, Cohen RA. Medical management of uric acid stones. In: Han H, Mutter WP, Nasser S, eds. Nutritional and Medical Management of Kidney Stones. Springer International Publishing; 2019.National Institute for Health and Care Excellence. Drug allergy: diagnosis and management of drug allergy in adults, children and young people. https://www.nice.org.uk/guidance/cg183. Published September 2014. Accessed November 19, 2020.Ng CY, Yeh YT, Wang CW, et al. Impact of the HLA-B(*)58:01 allele and renal impairment on allopurinol-induced cutaneous adverse reactions. J Invest Dermatol. 2016;136(7):1373-1381. doi:10.1016/j.jid.2016.02.808 [PubMed 26996548]Park HJ, Yun J, Kang DY, et al. Unique clinical characteristics and prognosis of allopurinol-induced severe cutaneous adverse reactions. J Allergy Clin Immunol Pract. 2019;7(8):2739-2749.e3. doi:10.1016/j.jaip.2019.05.047 [PubMed 31201937]Patel AV, Gaffo AL. Managing gout in women: current perspectives. J Inflamm Res. 2022;15:1591-1598. doi:10.2147/JIR.S284759 [PubMed 35264868]Perez-Ruiz F. Pharmacologic urate-lowering therapy and treatment of tophi in patients with gout. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 19, 2022.Polimeni G, Cardillo R, Garaffo E, et al. Allopurinol-induced Sweet's syndrome. Int J Immunopathol Pharmacol. 2016;29(2):329-332. doi:10.1177/0394632015599705 [PubMed 26684631]Qaseem A, Harris RP, Forciea MA; Clinical Guidelines Committee of the American College of Physicians. Management of acute and recurrent gout: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2017;166(1):58-68. doi:10.7326/M16-0570 [PubMed 27802508]Quach C, Galen BT. HLA-B*5801 testing to prevent allopurinol hypersensitivity syndrome: a teachable moment. JAMA Intern Med. 2018;178(9):1260-1261. doi:10.1001/jamainternmed.2018.3556 [PubMed 30083702]Ramasamy SN, Korb-Wells CS, Kannangara DR, et al. Allopurinol hypersensitivity: a systematic review of all published cases, 1950-2012. Drug Saf. 2013;36(10):953-980. doi:10.1007/s40264-013-0084-0 [PubMed 23873481]Raper R, Ibels L, Lauer C, Barnes P, Lunzer M. Fulminant hepatic failure due to allopurinol. Aust N Z J Med. 1984;14(1):63-65. doi:10.1111/j.1445-5994.1984.tb03591.x [PubMed 6590011]Refer to manufacturer's labeling.Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2017;76(1):29-42. doi:10.1136/annrheumdis-2016-209707 [PubMed 27457514]Saito Y, Stamp LK, Caudle KE, et al; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for human leukocyte antigen B (HLA-B) genotype and allopurinol dosing: 2015 update. Clin Pharmacol Ther. 2016;99(1):36-37. doi:10.1002/cpt.161 [PubMed 26094938]Santos-Victoriano M, Brouhard BH, Cunningham RJ 3rd. Renal stone disease in children. Clin Pediatr (Phila). 1998;37(10):583-599. [PubMed 9793728]Schrijvers R, Gilissen L, Chiriac AM, Demoly P. Pathogenesis and diagnosis of delayed-type drug hypersensitivity reactions, from bedside to bench and back. Clin Transl Allergy. 2015;5:31. doi:10.1186/s13601-015-0073-8 [PubMed 26339470]Serikawa T, Abe T, Minamikawa T, et al. A case report of fatal tumor lysis syndrome after chemotherapy in a pregnant patient with Burkitt's lymphoma. J Obstet Gynaecol Res. 2011;37(8):1141-1144. doi:10.1111/j.1447-0756.2010.01485.x [PubMed 21481095]Shankar P, Aish L, Hassoun H. Allopurinol-induced pure red cell aplasia. Am J Hematol. 2003;73(1):69. doi:10.1002/ajh.10315 [PubMed 12701126]Sheikh M, Nelson-Piercy C, Duley J, Florin T, Ansari A. Successful pregnancies with thiopurine-allopurinol co-therapy for inflammatory bowel disease. J Crohns Colitis. 2015;9(8):680-684. doi:10.1093/ecco-jcc/jjv072 [PubMed 25939351]Simsek M, Opperman RCM, Mulder CJJ, Lambalk CB, de Boer NKH. The teratogenicity of allopurinol: a comprehensive review of animal and human studies. Reprod Toxicol. 2018;81:180-187. doi:10.1016/j.reprotox.2018.08.012 [PubMed 30125681]Stamp LK, Barclay ML. How to prevent allopurinol hypersensitivity reactions? Rheumatology (Oxford). 2018;57(suppl 1):i35-i41. doi:10.1093/rheumatology/kex422 [PubMed 29272508]Stamp LK, Day RO, Yun J. Allopurinol hypersensitivity: investigating the cause and minimizing the risk. Nat Rev Rheumatol. 2016;12(4):235-242. doi: 10.1038/nrrheum.2015.132. Erratum in: Nat Rev Rheumatol. 2016;12(4):i. [PubMed 26416594]Stamp LK, Taylor WJ, Jones PB, et al. Starting dose is a risk factor for allopurinol hypersensitivity syndrome: a proposed safe starting dose of allopurinol. Arthritis Rheum. 2012;64(8):2529-2536. doi:10.1002/art.34488 [PubMed 22488501]Strilchuk L, Fogacci F, Cicero AF. Safety and tolerability of available urate-lowering drugs: a critical review. Expert Opin Drug Saf. 2019;18(4):261-271. doi:10.1080/14740338.2019.1594771 [PubMed 30915866]Torrance HL, Benders MJ, Derks JB, et al. Maternal allopurinol during fetal hypoxia lowers cord blood levels of the brain injury marker S-100B. Pediatrics. 2009;124(1):350-357. doi:10.1542/peds.2008-2228 [PubMed 19564319]Torres RJ, Prior C, Puig JG. Efficacy and safety of allopurinol in patients with hypoxanthine-guanine phosphoribosyltransferase deficiency. Metabolism. 2007a;56(9):1179-1186. [PubMed 17697859]Torres RJ, Puig JG. Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome. Orphanet J Rare Dis. 2007b;2:48. [PubMed 18067674]van Veen TR, Haeri S. Gout in pregnancy: a case report and review of the literature. Gynecol Obstet Invest. 2015;79(4):217-221. doi:10.1159/000369999 [PubMed 25660596]Vargas-Santos AB, Neogi T. Management of gout and hyperuricemia in CKD. Am J Kidney Dis. 2017;70(3):422-439. doi: 10.1053/j.ajkd.2017.01.055 [PubMed 28456346]Wang CW, Dao RL, Chung WH. Immunopathogenesis and risk factors for allopurinol severe cutaneous adverse reactions. Curr Opin Allergy Clin Immunol. 2016;16(4):339-345. doi:10.1097/ACI.0000000000000286 [PubMed 27362322]World Health Organization. Breastfeeding and maternal medication: recommendations for drugs in the eleventh WHO model list of essential drugs. 2002. https://apps.who.int/iris/handle/10665/62435Wortmann RL, Macdonald PA, Hunt B, Jackson RL. Effect of prophylaxis on gout flares after the initiation of urate-lowering therapy: analysis of data from three phase III trials. Clin Ther. 2010;32(14):2386-2397. doi:10.1016/j.clinthera.2011.01.008 [PubMed 21353107]Wright DF, Doogue MP, Barclay ML, et al. A population pharmaco*kinetic model to predict oxypurinol exposure in patients on haemodialysis. Eur J Clin Pharmacol. 2017;73(1):71-78. doi:10.1007/s00228-016-2133-y [PubMed 27683090]Yang CY, Chen CH, Deng ST, et al. Allopurinol use and risk of fatal hypersensitivity reactions: a nationwide population-based study in Taiwan. JAMA Intern Med. 2015;175(9):1550-1557. doi:10.1001/jamainternmed.2015.3536 [PubMed 26193384]Yeo E, Palmer SC, Chapman PT, Frampton C, Stamp LK. Serum urate levels and therapy in adults treated with long-term dialysis: a retrospective cross-sectional study. Intern Med J. 2019;49(7):838-842. doi:10.1111/imj.14163 [PubMed 30426652]Yokose C, Lu N, Xie H, et al. Heart disease and the risk of allopurinol-associated severe cutaneous adverse reactions: a general population-based cohort study. CMAJ. 2019;191(39):E1070-E1077. doi:10.1503/cmaj.190339 [PubMed 31570545]Zyloprim (allopurinol) tablets [prescribing information]. East Brunswick, NJ: Casper Pharma LLC; August 2022.Zyloprim (allopurinol) [product monograph]. Vaughan, Ontario, Canada: AA Pharma Inc; September 2021.Topic 8439 Version 472.0

CloseAllopurinol: Pediatric drug informationAllopurinol: Pediatric drug information(For additional information see "Allopurinol: Drug information" and see "Allopurinol: Patient drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USAloprim;ZyloprimBrand Names: CanadaAG-Allopurinol;APO-Allopurinol;GEN-Allopurinol;JAMP-Allopurinol;Mar-Allopurinol;ZyloprimTherapeutic CategoryAntigout Agent;Uric Acid Lowering AgentDosing: PediatricNote: Dosing presenting in multiple formats (mg/m2/dose, mg/m2/day, mg/kg/day, and a fixed mg dose); take extra precautions to ensure accuracy. Before prescribing allopurinol, consider testing for the HLA-B*5801 allele in patients at elevated risk for developing severe cutaneous adverse reactions (SCAR) (including Koreans with CKD ≥ stage 3 and all patients of Han Chinese or Thai descent). A negative HLA-B*5801 genetic test, however, does not entirely rule out the possibility of allopurinol-associated SCAR, so patients should still be appropriately monitored for SCAR, as well as other forms of hypersensitivity (Ref).Hyperuricemia associated with chemotherapy managementHyperuricemia associated with chemotherapy management: Maintain adequate hydration; begin allopurinol 1 to 2 days before initiation of induction chemotherapy; may continue for 3 to 7 days after chemotherapy (Ref); daily doses >300 mg should be administered in divided doses:Oral:Manufacturer's labeling:Children <6 years: 150 mg daily.Children 6 to 10 years: 300 mg daily.Children >10 years and Adolescents: 600 to 800 mg daily for 2 to 3 days in 2 to 3 divided doses.Alternate dosing: Tumor lysis syndrome; intermediate-risk: Limited data available (Ref): Infants, Children, and Adolescents:Weight-directed dosing: 10 mg/kg/day divided every 8 hours; maximum daily dose: 800 mg/day.BSA-directed dosing: 50 to 100 mg/m2/dose every 8 hours; maximum daily dose: 300 mg/m2/day.IV: For patients unable to tolerate oral therapy (BSA-directed dosing):Manufacturer's labeling: Children and Adolescents: Initial: 200 mg/m2/day administered once daily or in equally divided doses at 6-, 8-, or 12-hour intervals.Alternate dosing: Tumor lysis syndrome; intermediate-risk: Limited data available: Infants, Children, and Adolescents: 200 to 400 mg/m2/day in 1 to 3 divided doses; maximum daily dose: 600 mg/day (Ref).Hyperuricemia associated with inborn errors of purine metabolismHyperuricemia associated with inborn errors of purine metabolism (Lesch-Nyhan syndrome): Limited data available: Oral: Infants, Children, and Adolescents: Initial: 5 to 10 mg/kg/day; adjust dose to maintain a high-normal serum uric acid concentration and a urinary uric acid/creatinine ratio <1; reported range: 3.7 to 9.7 mg/kg/day; usual maximum daily dose: 600 mg/day (Ref).Recurrent calcium oxalate renal stonesRecurrent calcium oxalate renal stones (including glycogen storage disease): Limited data available: Oral: Children and Adolescents: 4 to 10 mg/kg/day in divided doses 3 to 4 times daily; maximum daily dose: 300 mg/day (Ref).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricAllopurinol and oxypurinol are dialyzable.Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, the following guidelines have been used by some clinicians:Management of hyperuricemia associated with chemotherapy: Oral, IV:Aronoff 2007:GFR 30 to 50 mL/minute/1.73 m2: Administer 50% of normal dose.GFR 10 to 29 mL/minute/1.73 m2: Administer 50% of normal dose.GFR <10 mL/minute/1.73 m2: Administer 30% of normal dose.Intermittent hemodialysis: Administer 30% of normal dose.Peritoneal dialysis: Administer 30% of normal dose.Continuous renal replacement therapy (CRRT): Administer 50% of normal dose.Coiffier 2008: Dosage reduction of 50% is recommended in renal impairment.Dosing: Hepatic Impairment: PediatricThere are no dosage adjustments provided in the manufacturer's labeling.Dosing: Adult(For additional information see "Allopurinol: Drug information")Note: Before prescribing allopurinol, testing for the HLA-B*5801 allele in patients at elevated risk for developing severe cutaneous adverse reactions (SCAR) (patients of Asian descent [eg, Korean, Han Chinese, Thai] and African American patients) is recommended (Ref). A negative HLA-B*5801 genetic test, however, does not entirely rule out the possibility of allopurinol-associated SCAR, so patients should still be appropriately monitored for SCAR, as well as other forms of hypersensitivity (Ref). Use should be avoided in any patient testing positive for the allele (Ref).Gout, treatmentGout, treatment (chronic urate-lowering therapy): Oral: Note: Urate-lowering therapy may be initiated during a gout flare or after the flare subsides; concomitant pharmacologic prophylaxis with colchicine, NSAIDS, or a glucocorticoid is recommended for at least the first 3 to 6 months to decrease flare activity (Ref).Initial: 100 mg once daily (Ref).Dosage adjustments: Titrate in 100 mg increments every 2 to 4 weeks to achieve the desired serum uric acid level (Ref).Maintenance: Doses ≥300 mg/day are usually needed to reach the desired uric acid target; doses up to 800 mg/day may be required (Ref).Maximum: 800 mg/dayFrequency of administration: Once daily in a single dose or in 2 or 3 divided doses. Note: The manufacturer's labeling recommends doses >300 mg be given in divided doses; however, most experts prescribe a single daily dose, regardless of total dose administered, except during a brief period (eg, when initiating or titrating therapy) when divided doses may help improve GI tolerability (Ref).Nephrolithiasis, prevention of recurrent calcium or uric acid stonesNephrolithiasis, prevention of recurrent calcium or uric acid stones: Due to calcium oxalate stones: Patients with hyperuricosuria (who continue to have active disease despite attempted dietary modification): Oral: 300 mg/day, usually given in a single daily dose but may be given in 2 or 3 divided doses, if needed, to improve GI tolerability (Ref).Due to uric acid stones (off-label use): Oral: 300 mg/day, usually given in a single daily dose but may be given in 2 or 3 divided doses, if needed, to improve GI tolerability; use is reserved for patients who continue to have active disease despite urinary alkalinization therapy and increased hydration (Ref).Tumor lysis syndrome, preventionTumor lysis syndrome, prevention: Patients at intermediate risk for tumor lysis syndrome (TLS) and without preexisting hyperuricemia (serum uric acid ≥8 mg/dL [476 micromol/L]):Note: Aggressive IV hydration should always be initiated prior to cytotoxic therapy in patients at elevated risk for TLS (Ref).Oral: 300 mg/m2/day or 10 mg/kg/day, given in 3 divided doses every 8 hours (maximum: 800 mg/day). Begin therapy 1 to 2 days before the start of induction chemotherapy and may continue for up to 3 to 7 days after chemotherapy until normalization of laboratory evidence of TLS (eg, serum uric acid, serum LDH) (Ref).IV: 200 to 400 mg/m2/day, given in a single daily dose or in 2 or 3 divided doses (maximum: 600 mg/day). Begin therapy 1 to 2 days before the start of induction chemotherapy and may continue for 3 to 7 days after chemotherapy until normalization of laboratory evidence of TLS (eg, serum uric acid, serum LDH) (Ref).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultThe renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.Note: Renal impairment, particularly when a higher allopurinol starting dose and/or concomitant diuretics are used, is a risk factor for allopurinol hypersensitivity syndrome (AHS), a rare but potentially life-threatening systemic syndrome (Ref). In addition, the HLA-B*5801 allele is associated with an increased risk of allopurinol-induced severe cutaneous adverse reactions; patients of Korean, Han Chinese, or Thai descent are at increased risk for carrying this allele. Avoid allopurinol in any patient testing positive for this allele (Ref).To minimize the risk of AHS in patients with renal impairment (in the absence of the HLA-B*5801 allele or in those not at high risk for carrying this allele), the following dosage adjustments are recommended:Gout, treatment (chronic urate-lowering therapy): Oral:Altered kidney function:eGFR >60 mL/minute: No dosage adjustment necessary (Ref).eGFR ≤60 mL/minute:Initial: <100 mg daily (Ref); to lower the risk of AHS, some experts recommend not exceeding an initial dose of ~1.5 mg of allopurinol per mL/minute of eGFR (eg, for an eGFR of 50 mL/minute/1.73 m2, the initial dose should not exceed 75 mg daily; see table for suggested initial doses) (Ref).Allopurinol: Suggested Initial Doses in Kidney ImpairmentaeGFR mL/minute/1.73 m2Suggested initial doseaACR (FitzGerald 2020); Perez-Ruiz 2022; Stamp 2012; Vargas-Santos 2017.>30 to 6050 mg daily>15 to 3050 mg every other day5 to 1550 mg twice weekly<550 mg once weeklyTitration and maintenance: Gradually increase dose in ≤100 mg/day increments every 2 to 4 weeks; use of lower dose increments (ie, ≤50 mg/day) and longer intervals (ie, ≥4 weeks) may be preferred (Ref). Some experts delay the initial dose increase for 1 to 2 months until after peak risk for AHS has passed (Ref). Titrate to the minimum daily dose necessary to achieve goal urate-lowering effect. Doses >300 mg daily may be considered with appropriate patient education and monitoring for potential toxicity (eg, rash, pruritus, elevated transaminases) (Ref). If desired serum uric acid level cannot be achieved, conversion to an alternative agent may be considered (Ref).Hemodialysis, intermittent (thrice weekly): Dialyzable (oxypurinol): ~39% to 50% (Ref).Initial: 100 mg 3 times weekly administered post-dialysis (Ref).Titration and maintenance: Gradually increase dose in ≤50 mg/day increments (eg, 150 mg 3 times weekly) every 2 to 5 weeks. Some experts delay the initial dose increase for 1 to 2 months until after peak risk for AHS has passed (Ref). Titrate to the minimum dose necessary to achieve goal urate-lowering effect (Ref). Doses >300 mg daily may be considered with appropriate patient education and monitoring for potential toxicity (eg, rash, pruritus, elevated transaminases) (Ref); doses up to ~400 mg daily have been reported (Ref).Peritoneal dialysis:Initial: 50 mg daily; gradually increase dose in ≤50 mg/day increments every 2 to 5 weeks; titrate to the minimum daily dose necessary to achieve goal urate-lowering effect (Ref). Some experts delay the initial dose increase for 1 to 2 months until after peak risk for AHS has passed (Ref). Doses >300 mg daily may be considered with appropriate patient education and monitoring for potential toxicity (eg, rash, pruritus, elevated transaminases) (Ref).Nephrolithiasis, prevention of recurrent calcium or uric acid stones: Oral: Use a lower initial dose with gradual titration (Ref); for dosing guidance refer to gout treatment renal impairment dosing recommendations; not to exceed usual adult dose for nephrolithiasis.Tumor lysis syndrome, prevention: IV, Oral: Dosage reduction of 50% is recommended in renal impairment (Ref).Dosing: Hepatic Impairment: AdultThere are no dosage adjustments provided in the manufacturer's labeling.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution Reconstituted, Intravenous, as sodium [strength expressed as base]: Generic: 500 mg (1 ea)Solution Reconstituted, Intravenous, as sodium [strength expressed as base, preservative free]: Aloprim: 500 mg (1 ea)Generic: 500 mg (1 ea)Tablet, Oral: Zyloprim: 100 mg [scored]Zyloprim: 300 mg [scored; contains corn starch, fd&c yellow #6(sunset yellow)alumin lake]Generic: 100 mg, 200 mg, 300 mgGeneric Equivalent Available: USYesDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Tablet, Oral: Zyloprim: 100 mg, 200 mg, 300 mgGeneric: 100 mg, 200 mg, 300 mgAdministration: PediatricNote: Fluid intake should be sufficient to yield neutral or slightly alkaline (preferably) urine and a daily urine output of at least 2 L in adults.Oral: Administer after meals with plenty of fluidParenteral: The rate of infusion is dependent upon the volume of the infusion; infuse maximum single daily doses (600 mg/day) over ≥30 minutes; whenever possible, therapy should be initiated at 12 to 24 hours (pediatric patients) or 24 to 48 hours (adults) before the start of chemotherapy known to cause tumor lysis (including adrenocorticosteroids) (Ref). Intravenous daily therapy can be administered as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals.Administration: AdultOral: Administer after meals.IV: The rate of infusion depends on the volume of the infusion. IV daily dose can be administered as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals (Ref).Tumor lysis syndrome prevention: Administer aggressive fluids sufficient to maintain adequate hydration and urinary output; whenever possible, allopurinol therapy should be initiated 24 to 48 hours before the start of chemotherapy (and other treatments) known to cause tumor lysis (Ref).Other indications: Administer fluids sufficient to yield daily urinary output of at least 2 L and to maintain a neutral or, preferably, slightly alkaline urine.Storage/StabilityPowder for injection: Store intact vials at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Following preparation, IV solutions in NS or D5W should be stored at 20°C to 25°C (68°F to 77°F). Do not refrigerate reconstituted and/or diluted product. Must be administered within 10 hours of solution preparation.Tablet: Store at 15°C to 25°C (59°F to 77°F). Store in a dry place. Protect from light.UseOral: Management of hyperuricemia associated with cancer treatment for leukemia, lymphoma, or solid tumor malignancies (FDA approved in pediatric patients [age not specified] and adults); management of primary or secondary gout (acute attack, tophi, joint destruction, uric acid lithiasis, and/or nephropathy) (FDA approved in adults); management of recurrent calcium oxalate calculi (with uric acid excretion >800 mg/day in men and >750 mg/day in women) (FDA approved in adults); has also been used for treatment of hyperuricemia associated with inborn errors of purine metabolism (Lesch-Nyhan syndrome) and recurrent calcium oxalate calculi associated with glycogen storage disease.IV: Management of hyperuricemia associated with cancer treatment for leukemia, lymphoma, or solid tumor malignancies who cannot tolerate oral therapy (FDA approved in children and adults).Medication Safety IssuesSound-alike/look-alike issues: Allopurinol may be confused with Apresoline Zyloprim may be confused with zolpidem, ZORprin, ZoviraxAdverse Reactions (Significant): ConsiderationsAcute gout attacksAcute gout attacks have been reported during the early stages of allopurinol administration even when normal or optimal serum uric acid levels have been attained. Gout attacks generally decrease in duration and severity after several months of urate-lowering therapy (Ref).Mechanism: Dose-related; related to the pharmacologic action. Decrease in serum urate leads to the dissolution of monosodium urate crystal deposits and dispersion of crystals, causing gout flares (Ref).Onset: Varied; most likely to occur within first 6 months of treatment (Ref); risk is lower after 1 year of treatment (Ref).Risk factors:• Early in course of treatment (Ref)• Initiating urate-lowering treatment without concurrent gout flare prophylaxis (Ref)• Withdrawal of anti-inflammatory gout flare prophylaxis (Ref)• Uric acid >6 mg/dL during treatment (Ref)• Rapid decreases and/or greater reduction in uric acid (Ref)• Persistence of tophi (Ref)HepatotoxicityMost cases of acute hepatotoxicity with allopurinol are associated with drug reaction with eosinophilia and systemic symptoms (DRESS) and allopurinol hypersensitivity syndrome (Ref). May rarely occur without any features of DRESS (Ref). The pattern of liver enzyme elevations is usually hepatocellular or mixed, but can be cholestatic (Ref).Mechanism: Non-dose-related; immunologic. DRESS syndrome is T-cell-mediated (Ref).Onset: Varied; usually occur 1 to 5 weeks after initiation (Ref).Risk factors:• African-American race (Ref)• Preexisting kidney disease (Ref)Hypersensitivity reactions (delayed)Allopurinol is associated with a variety of delayed hypersensitivity reactions (often termed allopurinol hypersensitivity syndrome [AHS]), ranging from mild maculopapular rash to severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) (Ref).Mechanism: Non-dose-related; immunologic. Delayed hypersensitivity reactions, including maculopapular eruptions and SCARs are T-cell-mediated (Ref).Onset: Delayed hypersensitivity reactions: varied; usually occur 3 to 9 weeks after initiation (Ref), but may occur more rapidly (usually within 1 to 4 days) upon reexposure (Ref).Risk factors:• Presence of HLA-B*5801 allele is strongly associated with SCARs, especially with concomitant kidney impairment and in some Asian populations (Ref). HLA-A*3303 and HLA-C*0302 alleles are associated with SJS or TEN, especially in Asian populations (Ref)• Dose (Ref)• Kidney impairment: Correlated to delayed clearance of oxypurinol (metabolite of allopurinol) and potentially high levels of granulysin (Ref)• Older adults (≥60 years of age), possibly due to kidney impairment (Ref)• Females (Ref)• Asymptomatic hyperuricemia, especially in patients with concomitant kidney or cardiovascular disease (Ref)• Concomitant cardiovascular disease (Ref)• Concomitant diuretic use: Although diuretic use has been associated with increased risk of allopurinol hypersensitivity reactions (Ref), some studies have not found an association between diuretic use and AHS (Ref)• Cross-reactivity between allopurinol and febuxostat: Although there may be an increased risk of a skin reaction with febuxostat in patients with a history of reactions to allopurinol, whether this represents 2 separate reactions or cross-reactivity is not known (Ref)Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.1% to 10%:Dermatologic: Maculopapular rash (≤3%; pruritic), skin rash (≤2%)Gastrointestinal: Nausea (1%), vomiting (≤1%)Neuromuscular & skeletal: Gout (≤6%; acute)Renal: Renal failure syndrome (≤1%)<1%:Cardiovascular: Bradycardia, edema, flushing, heart failure, hypertension, hypotension, low cardiac output, necrotizing angiitis, pericarditis, peripheral vascular disease, pulmonary embolism, septic shock, thrombophlebitis, vasculitis, vasodilation, ventricular fibrillationDermatologic: Alopecia, cellulitis, diaphoresis, ecchymoses, eczema, exfoliative dermatitis, furunculosis, lichen planus, onycholysis, purpuric rash, skin edema, Stevens-Johnson syndrome (Gupta 2019), toxic epidermal necrolysis (Hoyer 2021), urticaria, vesicobullous dermatitisEndocrine & metabolic: Albuminuria, decreased libido, gynecomastia, hypercalcemia, hyperglycemia, hyperkalemia, hyperlipidemia, hypernatremia, hyperphosphatemia, hyperuricemia, hypervolemia, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, lactic acidosis, metabolic acidosis, water intoxicationGastrointestinal: Abdominal pain, ageusia, anorexia, constipation, dysgeusia, dyspepsia, enlargement of abdomen, enlargement of salivary glands, flatulence, gastritis, gastrointestinal hemorrhage, hemorrhagic pancreatitis, intestinal obstruction, proctitis, stomatitisGenitourinary: Glycosuria, hematuria, impotence, male infertility, oliguria, uremia, urinary tract infectionHematologic & oncologic: Agranulocytosis, anemia, aplastic anemia, bone marrow aplasia, bone marrow depression, chronic myelocytic leukemia, disseminated intravascular coagulation, eosinophilia, eosinophilic fibrohistiocytic bone marrow lesion, hemolytic anemia, hemorrhage, hypoprothrombinemia, leukocytosis, leukopenia, lymphadenopathy, lymphocytosis, neutropenia, pancytopenia, reticulocytosis, splenomegaly, thrombocytopenia, tumor lysis syndromeHepatic: Cholestatic jaundice, granulomatous hepatitis, hepatic failure, hepatic necrosis, hepatomegaly (Childs 2012), hepatotoxicity (Chalasani 2021), hyperbilirubinemia, jaundiceHypersensitivity: Drug reaction with eosinophilia and systemic symptoms (Chung 2015), facial edema, hypersensitivity angiitis, tongue edemaInfection: Infection, sepsisLocal: Injection-site reactionNervous system: Agitation, amnesia, asthenia, cerebral infarction, cerebrovascular accident, chills, coma, confusion, depression, dizziness, drowsiness, dystonia, headache, hypotonia, insomnia, malaise, mental status changes, myoclonus, neuritis, pain, paralysis, paresthesia, peripheral neuropathy, seizure, status epilepticus, tremor, twitching, vertigoNeuromuscular & skeletal: Arthralgia, foot-drop, myalgia, myopathyOphthalmic: Amblyopia, cataract, conjunctivitis, iritis, macular retinitis, optic neuritisOtic: TinnitusRenal: Nephritis (including interstitial nephritis) (Gelbart 1977)Respiratory: Acute respiratory distress syndrome, apnea, asthma, bronchospasm, epistaxis, pharyngitis, respiratory failure, rhinitis, tachypneaMiscellaneous: FeverFrequency not defined:Gastrointestinal: DiarrheaHepatic: Increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferasePostmarketing:Dermatologic: Sweet syndrome (Polimeni 2016)Hematologic & oncologic: Pure red cell aplasia (Shankar 2003)Hypersensitivity: Hypersensitivity reaction (allopurinol hypersensitivity syndrome; can be severe hypersensitivity reaction) (Chen 2005)ContraindicationsSevere hypersensitivity reaction to allopurinol or any component of the formulation.Canadian labeling: Additional contraindications (not in the US labeling): Breastfeeding mothers and children (except those with cancer therapy-induced hyperuricemia or Lesch-Nyhan syndrome).Note: To avoid the risk of severe cutaneous adverse reactions (SCAR), HLA-B*5801-positive patients should avoid allopurinol (Perez-Ruiz 2022; Saito 2016). The American College of Rheumatology recommends HLA-B*5801 screening in patients at elevated risk of SCAR, including patients of Asian descent (eg, Korean, Han Chinese, Thai) and African American patients (ACR [FitzGerald 2020]).Warnings/PrecautionsConcerns related to adverse effects:• CNS effects: May occasionally cause drowsiness; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).Disease-related concerns:• Renal impairment: Dose reductions are recommended in patients with renal impairment; monitor closely. Some patients with preexisting renal disease or poor urate clearance have shown a rise in BUN with allopurinol. Patients with renal impairment should be carefully monitored during the early stages of allopurinol treatment; reduce the dose or withdraw therapy if increased renal function abnormalities appear and persist. Renal failure associated with allopurinol has been observed in patients with hyperuricemia secondary to neoplastic diseases. Concurrent conditions including multiple myeloma and congestive myocardial disease were present among patients whose renal dysfunction increased after allopurinol was begun. Renal failure is also frequently associated with gouty nephropathy. Albuminuria has been observed among patients who developed clinical gout following chronic glomerulonephritis and chronic pyelonephritis.Other warnings/precautions:• Hydration: For tumor lysis syndrome prevention, administer aggressive fluids sufficient to maintain adequate hydration and urinary output (Coiffier 2008). For other indications, fluid intake sufficient to yield a daily urinary output of at least 2 L and maintenance of a neutral or (preferably) a slightly alkaline urine are desirable in order to avoid possible formation of xanthine calculi due to allopurinol therapy and to help prevent renal urate precipitation in patients receiving concomitant uricosuric agents.Metabolism/Transport EffectsNone known.Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions programAluminum Hydroxide: May decrease the serum concentration of Allopurinol. Management: Consider administering allopurinol 3 hours prior to aluminum hydroxide. Risk D: Consider therapy modificationAmoxicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Amoxicillin.Risk C: Monitor therapyAmpicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Ampicillin.Risk C: Monitor therapyAngiotensin-Converting Enzyme Inhibitors: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk C: Monitor therapyAzaTHIOprine: Allopurinol may increase serum concentrations of the active metabolite(s) of AzaTHIOprine. More specifically, allopurinol may increase mercaptopurine serum concentrations and promote formation of active thioguanine nucleotides.Management: Reduce azathioprine dose to one third to one quarter of the usual dose if used with allopurinol, and monitor closely for systemic toxicity. Further dose reduction or alternative therapies should be considered for patients with low or absent TPMT activity. Risk D: Consider therapy modificationBacampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Bacampicillin.Risk C: Monitor therapyBendamustine: Allopurinol may enhance the adverse/toxic effect of Bendamustine. Specifically, the risk of severe skin reactions may be enhanced.Risk C: Monitor therapyCarBAMazepine: Allopurinol may increase the serum concentration of CarBAMazepine.Risk C: Monitor therapyCyclophosphamide: Allopurinol may increase the serum concentration of Cyclophosphamide.Risk C: Monitor therapyCycloSPORINE (Systemic): Allopurinol may increase the serum concentration of CycloSPORINE (Systemic).Risk C: Monitor therapyDidanosine: Allopurinol may increase the serum concentration of Didanosine.Risk X: Avoid combinationDoxofylline: Allopurinol may increase the serum concentration of Doxofylline.Risk C: Monitor therapyFluorouracil Products: Allopurinol may decrease serum concentrations of the active metabolite(s) of Fluorouracil Products.Risk X: Avoid combinationLoop Diuretics: May enhance the adverse/toxic effect of Allopurinol. Loop Diuretics may increase the serum concentration of Allopurinol. Specifically, Loop Diuretics may increase the concentration of Oxypurinol, an active metabolite of Allopurinol. Risk C: Monitor therapyMercaptopurine: Allopurinol may increase the serum concentration of Mercaptopurine. Allopurinol may also promote formation of active thioguanine nucleotides.Management: Reduce the mercaptopurine dose to one third to one quarter of the usual dose if used with allopurinol, and monitor closely for systemic toxicity. Risk D: Consider therapy modificationPegloticase: Allopurinol may enhance the adverse/toxic effect of Pegloticase. Specifically, Allopurinol may blunt increases in serum urate that would signal an increased risk of anaphylaxis and infusion reactions.Risk X: Avoid combinationRiluzole: Allopurinol may enhance the adverse/toxic effect of Riluzole. Specifically, the risk of hepatotoxicity may be increased.Management: Consider alternatives to allopurinol in patients receiving treatment with riluzole due to the potential for additive hepatotoxicity. Risk D: Consider therapy modificationTheophylline Derivatives: Allopurinol may increase the serum concentration of Theophylline Derivatives.Risk C: Monitor therapyThiazide and Thiazide-Like Diuretics: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk C: Monitor therapyVitamin K Antagonists (eg, warfarin): Allopurinol may enhance the anticoagulant effect of Vitamin K Antagonists.Management: Monitor for increased prothrombin times (PT)/therapeutic effects of oral anticoagulants if allopurinol is initiated/dose increased, or decreased effects if allopurinol is discontinued/dose decreased. Reductions in coumarin dosage will likely be needed. Risk D: Consider therapy modificationDietary ConsiderationsFor tumor lysis syndrome prevention, administer aggressive fluids sufficient to maintain adequate hydration and urinary output (Coiffier 2008). For other indications, fluid intake should be administered to yield neutral or slightly alkaline urine and an output of ~2 L (in adults).Pregnancy ConsiderationsAllopurinol crosses the placenta.Following a single dose of allopurinol 500 mg IV immediately prior to delivery, allopurinol and the oxypurinol metabolite were present in cord blood (Kaandorp 2014; Torrance 2009).Outcome data following maternal use of allopurinol in pregnancy are limited. Based on similar adverse outcomes from 2 case reports, use during the first trimester is generally avoided until additional data are available. Close maternal and fetal monitoring is recommended when treatment with allopurinol is needed (El-Sonbaty 2001; Hoeltzenbein 2013; Jones 2021; Laube 2021; Patel 2022; Serikawa 2011; Sheikh 2015; Simsek 2018; van Veen 2015).Monitoring ParametersCBC, serum uric acid levels every 2 to 5 weeks during dose titration until desired level is achieved and every 6 months thereafter (ACR guidelines [Khanna 2012]), liver function tests (periodically in patients with preexisting hepatic disease), renal function (BUN, serum creatinine or creatinine clearance (periodically), prothrombin time [periodically in patients receiving warfarin]); consider HLA-B*5801 testing prior to initiation of therapy in patients at a higher risk for allopurinol hypersensitivity syndrome (ACR guidelines [Khanna 2012]). Monitor hydration status, for signs and symptoms of hypersensitivity, hepatotoxicityReference RangeChildren and Adolescents:Uric Acid Normal ValuesAgeNormal Serum Concentration1 to 3 years1.8 to 5 mg/dL4 to 6 years2.2 to 4.7 mg/dL7 to 9 years2 to 5 mg/dL10 to 11 yearsMaleFemale2.3 to 5.4 mg/dL3 to 4.7 mg/dL12 to 13 years: Male2.7 to 6.7 mg/dL14 to 15 years: Male2.4 to 7.8 mg/dL12 to 15 years: Female3 to 5.8 mg/dL16 to 19 yearsMaleFemale4 to 8.6 mg/dL3 to 5.9 mg/dLAdult:Males: 3.4 to 7 mg/dL or slightly moreFemales: 2.4 to 6 mg/dL or slightly moreTarget: ≤6 mg/dLIn adults, values >7 mg/dL are sometimes arbitrarily regarded as hyperuricemia, but there is no sharp line between normals on the one hand, and the serum uric acid of those with clinical gout. Normal ranges cannot be adjusted for purine ingestion, but high purine diet increases uric acid. Uric acid may be increased with body size, exercise, and stress.Mechanism of ActionAllopurinol inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine to uric acid. Allopurinol is metabolized to oxypurinol which is also an inhibitor of xanthine oxidase; allopurinol acts on purine catabolism, reducing the production of uric acid without disrupting the biosynthesis of vital purines.Pharmaco*kinetics (Adult data unless noted)Onset of action:Gout: Decrease in serum and urine uric acid: 2 to 3 days; peak effect: 1 week or longer; normal serum urate levels achieved typically within 1 to 3 weeks.Cancer therapy-induced hyperuricemia: Median time to plasma uric acid control: 27 hours (Cortes 2010).Absorption: Oral: 90% from GI tract.Distribution: Vss: ~0.87 ± 0.13 L/kg.Metabolism: Rapidly oxidized to active metabolites, primarily oxypurinol.Bioavailability: ~49% to 53%.Half-life elimination:Oral: Parent drug: ~1 to 2 hours; Oxypurinol: ~15 hours.IV: Parent drug: 1.21 ± 0.33 hours; Oxypurinol: 23.5 ± 4.5 hours.Time to peak, plasma: Oral: Allopurinol: 1.5 hours; Oxypurinol: 4.5 hours.Excretion: Urine (76% as oxypurinol, 12% as unchanged drug); feces (~20%).Extemporaneous Preparations20 mg/mL Oral Suspension:A 20 mg/mL oral suspension may be made with tablets and either a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of Ora-Sweet SF and Ora-Plus or a 1:4 mixture of cherry syrup concentrate and simple syrup, NF. Crush eight 300 mg tablets in a mortar and reduce to a fine powder. Add small portions of chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label “shake well.” Stable for 60 days refrigerated or at room temperature (Allen 1996; Nahata 2004).Allen LV Jr, Erickson MA 3rd. Stability of acetazolamide, allopurinol, azathioprine, clonazepam, and flucytosine in extemporaneously compounded oral liquids. Am J Health Syst Pharm. 1996;53(16):1944-1949.8862208Nahata MC, Pai VB, Hipple TF. Pediatric Drug Formulations. 5th ed. Cincinnati, OH: Harvey Whitney Books Co; 2004.Pricing: USSolution (reconstituted) (Allopurinol Sodium Intravenous)500 mg (per each): $3,480.00 - $4,680.00Solution (reconstituted) (Aloprim Intravenous)500 mg (per each): $4,784.47Tablets (Allopurinol Oral)100 mg (per each): $0.24 - $0.48200 mg (per each): $7.95300 mg (per each): $0.61 - $0.92Tablets (Zyloprim Oral)100 mg (per each): $3.98300 mg (per each): $11.19Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalAcepurin (NL);Adenock (JP);AL (PH);Alinol (TH);Allnol (HK);Allo (CO);Allo-Puren (DE);Allogut (TR);Allonol (LK);Allopin (TH);Allopur (CH, NO);Allopurinol-ratiopharm (LU);Alloric (TH);Alloril (IL);Allosig (AU);Allozym (JP);Allpargin (LU);Allurase (PH);Alluric (EG);Allurit (IT);Alopron (BM, BS, GY, JM, MT, SR, TR, TT);Alopur (IE);Alopurinol (HR);Aloric (BD);Alorinol (EG);Alositol (JP);Alpurase (PH);Alpuric (LU);Alpurin (PH);Alunlan (TW);Aluric (LB);Aluron (VE);Anoprolin (JP);Anzief (JP);Ao Mai Bi Li (CN);Aprinol (JP);Apronal (TH);Apurin (FI, GR);Apurol (SA);Atisuril (CR, DO, GT, HN, MX, NI, PA, SV);Aurinol (PH);Benoxuric (ID);Bleminal (DE);Caplenal (GB);Cellidrin (DE);Clint (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW);Dertrifort (CR, DO, GT, HN, NI, PA, SV);Etindrax (MX);Foligan (DE);Genozyl (MX);Gichtex (AT);Goutex (BD);Goutilex (TW);Hamarin (GB);Huma-Purol (HU);Isoric (ID);Ketanrift (JP);Ketobun-A (JP);Lessuric (EG);Litinol (VE);Llanol (VN);Logout (LK);Loric (SA);Loric-100 (BH, PH, QA);Loric-300 (BH, PH);Masaton (JP);Mensil (PY);Mephanol (AE, BF, BJ, CH, CI, CY, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZM, ZW);Milurit (BG, CZ, HU, SK);Miniplanor (JP);Neufan (JP);Nilapur (ID);Nipurol (VE);No-Uric (AE, BH, CY, ET, IQ, IR, JO, KW, LB, LY, OM, QA, SY, YE);Pritanol (ID);Progout (AU, SG);Puribel 300 (MX);Puricemia (ID);Puricos (ZA);Purinol (AE, BD, CZ, IE, JO, MY, QA, RU, SA, ZW);Remid (DE, PY);Riball (JP);Ridonra (TW);Rinolic (ID);Ripunin (TW);Sadapron (VN);Salterprim (ZA);Sinoric (ID);Takanarumin (JP);Tipuric (IE);Tonsaric (TW);Trianol (PH);Tylonic (ID);Unizuric (CR, DO, GT, HN, NI, PA, SV);Unizuric 300 (MX);Uranid (TW);Uric (JP);Uricad (TH);Uriconorm (CH);Urinol (MY);Urocuad (CO);Urogquad (AR);Uroquad (AE, BF, BJ, BM, BS, CI, ET, GH, GM, GN, GY, JM, KE, LR, MA, ML, MR, MU, MW, NE, NG, SA, SC, SD, SL, SN, SR, TN, TT, TZ, UG, ZM, ZW);Urosin (AT, DE, EC, LU);Valeric (CN);Xandase (TH);Xanol (TH);Xanurace (PH);Xoric (BD);Xylonol (TW);Yi Da Tong (CN);Zanuric (JO);Zylapour (GR);Zyloprim (AU, BB, BM, BS, CR, DO, GT, GY, HN, JM, MX, NI, PA, PH, PR, PY, SR, SV, TT);Zyloric (AE, BE, BF, BH, BJ, BR, CH, CI, CL, CY, DE, EE, EG, ES, ET, FI, FR, GB, GH, GM, GN, HK, ID, IE, IN, IQ, IR, IT, JO, KE, KR, KW, LB, LR, LU, LY, MA, ML, MR, MT, MU, MW, MY, NE, NG, NL, NO, OM, PK, PL, PT, QA, RU, SA, SC, SD, SE, SG, SK, SL, SN, SY, TH, TN, TR, TZ, UG, UY, VE, VN, YE, ZM, ZW);Zyngot (PE);Zyroric (KR)For country code abbreviations (show table)Adler NR, Aung AK, Ergen EN, Trubiano J, Goh MSY, Phillips EJ. Recent advances in the understanding of severe cutaneous adverse reactions. Br J Dermatol. 2017;177(5):1234-1247. doi:10.1111/bjd.15423 [PubMed 28256714]Al-Kawas FH, Seeff LB, Berendson RA, Zimmerman HJ, Ishak KG. Allopurinol hepatotoxicity. Report of two cases and review of the literature. Ann Intern Med. 1981;95(5):588-590. doi:10.7326/0003-4819-95-5-588 [PubMed 7294548]Allen LV, Erickson MA 3rd. Stability of Acetazolamide, Allopurinol, Azathioprine, Clonazepam, and Flucytosine in Extemporaneously Compounded Oral Liquids. Am J Health Syst Pharm. 1996;53(16):1944-1949. [PubMed 8862208]Allopurinol. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; February 24, 2015. [PubMed 31643428]Allopurinol tablet [prescribing information]. Morgantown, WV: Mylan Pharmaceuticals Inc; June 2015Aloprim (allopurinol) injection [prescribing information]. Morgantown, WV: Mylan Institutional LLC; February 2022.Appelbaum SJ, Mayersohn M, Dorr RT, et al. Allopurinol kinetics and bioavailability. Intravenous, oral and rectal administration. Cancer Chemother Pharmacol. 1982;8(1):93-98. [PubMed 7094203]Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th ed. American College of Physicians; 2007.Bardin T, Chalès G, Pascart T, et al. Risk of cutaneous adverse events with febuxostat treatment in patients with skin reaction to allopurinol. A retrospective, hospital-based study of 101 patients with consecutive allopurinol and febuxostat treatment. Joint Bone Spine. 2016;83(3):314-317. doi:10.1016/j.jbspin.2015.07.011 [PubMed 26709250]Becker MA, MacDonald PA, Hunt BJ, Lademacher C, Joseph-Ridge N. Determinants of the clinical outcomes of gout during the first year of urate-lowering therapy. Nucleosides Nucleotides Nucleic Acids. 2008;27(6):585-591. doi:10.1080/15257770802136032 [PubMed 18600509]Becker MA, Schumacher HR Jr, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005;353(23):2450-2461. doi:10.1056/NEJMoa050373 [PubMed 16339094]Blumenthal KG, Peter JG, Trubiano JA, Phillips EJ. Antibiotic allergy. Lancet. 2019;393(10167):183-198. doi:10.1016/S0140-6736(18)32218-9 [PubMed 30558872]Borstad GC, Bryant LR, Abel MP, Scroggie DA, Harris MD, Alloway JA. Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis. J Rheumatol. 2004;31(12):2429-2432. [PubMed 15570646]Brockow K, Przybilla B, Aberer W, et al. Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM). Allergo J Int. 2015;24(3):94-105. doi:10.1007/s40629-015-0052-6 [PubMed 26120552]Chalasani NP, Hayashi PH, Bonkovsky HL, et al. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2014;109(7):950-966. [PubMed 24935270]Chalasani NP, Maddur H, Russo MW, Wong RJ, Reddy KR; Practice parameters Committee of the American College of Gastroenterology. ACG clinical guideline: diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2021;116(5):878-898. doi:10.14309/ajg.0000000000001259 [PubMed 33929376]Chawla SK, Patel HD, Parrino GR, Soterakis J, Lopresti PA, D'Angelo WA. Allopurinol hepatotoxicity. Case report and literature review. Arthritis Rheum. 1977;20(8):1546-1549. doi:10.1002/art.1780200817 [PubMed 921828]Chen IH, Kuo MC, Hwang SJ, Chang JM, Chen HC. Allopurinol-induced severe hypersensitivity with acute renal failure. Kaohsiung J Med Sci. 2005;21(5):228-232. doi: 10.1016/S1607-551X(09)70192-5 [PubMed 15960069]Chen YC, Chiu HC, Chu CY. Drug reaction with eosinophilia and systemic symptoms: a retrospective study of 60 cases. Arch Dermatol. 2010;146(12):1373-1379. doi:10.1001/archdermatol.2010.198 [PubMed 20713773]Childs L, Dow C. Allopurinol-induced hepatomegaly. BMJ Case Rep. 2012;bcr2012007283. doi:10.1136/bcr-2012-007283 [PubMed 23087287]Choi HG, Byun J, Moon CH, et al. Allopurinol-induced DRESS syndrome mimicking biliary obstruction. Clin Mol Hepatol. 2014;20(1):71-75. doi:10.3350/cmh.2014.20.1.71 [PubMed 24757661]Chung WH, Chang WC, Stocker SL, et al. Insights into the poor prognosis of allopurinol-induced severe cutaneous adverse reactions: the impact of renal insufficiency, high plasma levels of oxypurinol and granulysin. Ann Rheum Dis. 2015;74(12):2157-2164. doi:10.1136/annrheumdis-2014-205577 [PubMed 25115449]Coiffier B, Altman A, Pui CH, Younes A, Cairo MS. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol 2008;26(16):2767-2778. [PubMed 18509186]Copelovitch L. Urolithiasis in children: medical approach. Pediatr Clin North Am. 2012;59(4):881-896. [PubMed 22857835]Cortes J, Moore JO, Maziarz RT, et al. Control of plasma uria acid in adults at risk for tumor lysis syndrome: efficacy and safety of rasburicase alone and rasburicase followed by allopurinol compared with allopurinol alone-results of a multicenter phase III study. J Clin Oncol. 2010;28(27):4207-4213. [PubMed 20713865]Curhan GC. Kidney stones in adults: Prevention of recurrent kidney stones. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 2, 2021.Curhan GC. Uric acid nephrolithiasis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 21, 2018.Currie WJ, Turmer P, Young JH. Evaluation of once a day allopurinol administration in man. Br J Clin Pharmacol. 1978;5(1):90-91. [PubMed 619943]Dalbeth N, Stamp L. Allopurinol dosing in renal impairment: walking the tightrope between adequate urate lowering and adverse events. Semin Dial. 2007;20(5):391-395. [PubMed 17897242]Day RO, Kannangara DR, Hayes JM, Furlong TJ. Successful use of allopurinol in a patient on dialysis. BMJ Case Rep. 2012;2012:bcr0220125814. doi:10.1136/bcr.02.2012.5814 [PubMed 22675142]Day RO, Kannangara DR, Stocker SL, Carland JE, Williams KM, Graham GG. Allopurinol: insights from studies of dose-response relationships. Expert Opin Drug Metab Toxicol. 2017;13(4):449-462. doi:10.1080/17425255.2017.1269745 [PubMed 27927043]El-Sonbaty MR, Bitar Z, Abdulrazak A. Acute spontaneous tumor-lysis syndrome in a pregnant woman with non-Hodgkin's lymphoma. Int J Hematol. 2001;73(3):386-389. doi:10.1007/BF02981967 [PubMed 11345208]Ettinger B, Tang A, Citron JT, Livermore B, Williams T. Randomized trial of allopurinol in the prevention of calcium oxalate calculi. N Engl J Med. 1986;315(22):1386-1389. doi: 10.1056/NEJM198611273152204. [PubMed 3534570]FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology guideline for the management of gout. Arthritis Care Res (Hoboken). 2020;72(6):744-760. doi:10.1002/acr.24180 [PubMed 32391934]FitzGerald JD, Mikuls TR, Neogi T, et al. Development of the American College of Rheumatology electronic clinical quality measures for gout. Arthritis Care Res (Hoboken). 2018;70(5):659-671. doi:10.1002/acr.23500 [PubMed 29649348]Gahart BL, Nazareno AR. 2012 Intravenous Medications: A Handbook for Nurses and Health Professionals. 28th ed. Elsevier/Mosby; 2012:58-59.Gelbart DR, Weinstein AB, Fajardo LF. Allopurinol-induced interstitial nephritis. Ann Intern Med. 1977;86(2):196-198. doi:10.7326/0003-4819-86-2-196 [PubMed 835946]Gupta SS, Sabharwal N, Patti R, Kupfer Y. Allopurinol-induced Stevens-Johnson syndrome. Am J Med Sci. 2019;357(4):348-351. doi:10.1016/j.amjms.2018.11.018 [PubMed 30638600]Hande KR, Noone RM, Stone WJ. Severe allopurinol toxicity. Description and guidelines for prevention in patients with renal insufficiency. Am J Med. 1984;76(1):47-56. doi:10.1016/0002-9343(84)90743-5 [PubMed 6691361]Hayes CP Jr, Metz EN, Robinson RR, Rundles RW. The use of allopurinol (HPP) to control hyperuricemia in patients on chronic intermittent hemodialysis. Trans Am Soc Artif Intern Organs. 1965;11:247-254. doi 10.1097/00002480-196504000-00047 [PubMed 14329092]Heilberg IP. Treatment of patients with uric acid stones. Urolithiasis. 2016;44(1):57-63. doi:10.1007/s00240-015-0843-8 [PubMed 26645868]Hershfield MS, Callaghan JT, Tassaneeyakul W, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing. Clin Pharmacol Ther. 2013;93(2):153-158. [PubMed 23232549]Hoeltzenbein M, Stieler K, Panse M, Wacker E, Schaefer C. Allopurinol Use during Pregnancy - Outcome of 31 Prospectively Ascertained Cases and a Phenotype Possibly Indicative for Teratogenicity. PLoS One. 2013;8(6):e66637. doi:10.1371/journal.pone.0066637 [PubMed 23840514]Hoyer D, Atti C, Nuding S, Vogt A, Sedding DG, Schott A. Toxic epidermal necrolysis caused by allopurinol: a serious but still underestimated adverse reaction. Am J Case Rep. 2021;22:e932921. doi:10.12659/AJCR.932921 [PubMed 34634004]Imai H, Kamei H, Onishi Y, et al. Successful living-donor liver transplantation for cholestatic liver failure induced by allopurinol: case report. Transplant Proc. 2015;47(9):2778-2781. doi:10.1016/j.transproceed.2015.09.038 [PubMed 26680093]Jennings CG, Mackenzie IS, Flynn R, et al; FAST study group. Up-titration of allopurinol in patients with gout. Semin Arthritis Rheum. 2014;44(1):25-30. doi:10.1016/j.semarthrit.2014.01.004 [PubMed 24560169]Jones AM, Tower C, Green D, Stepien KM. Multidisciplinary management of pregnancy and labour in a patient with glycogen storage disease type 1a. BMJ Case Rep. 2021;14(8):e241161. doi:10.1136/bcr-2020-241161 [PubMed 34380672]Kaandorp JJ, van den Broek MP, Benders MJ, et al; ALLO-trial Study Group. Rapid target allopurinol concentrations in the hypoxic fetus after maternal administration during labour. Arch Dis Child Fetal Neonatal Ed. 2014;99(2):F144-F148. doi:10.1136/archdischild-2013-304876 [PubMed 24352085]Kamilli I, Gresser U. Allopurinol and oxypurinol in human breast milk. Clin Investig. 1993;71(2):161-164. doi:10.1007/BF00179999 [PubMed 8461629]Keller SF, Lu N, Blumenthal KG, et al. Racial/ethnic variation and risk factors for allopurinol-associated severe cutaneous adverse reactions: a cohort study. Ann Rheum Dis. 2018;77(8):1187-1193. doi:10.1136/annrheumdis-2017-212905 [PubMed 29653927]Kenny JE, Goldfarb DS. Update on the pathophysiology and management of uric acid renal stones. Curr Rheumatol Rep. 2010;12(2):125-129. doi:10.1007/s11926-010-0089-y [PubMed 20425021]Khanna D, Fitzgerald JD, Khanna PP, et al; American College of Rheumatology. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012;64(10):1431-1446. [PubMed 23024028]Kliegman RM, Stanton BF, St. Gemell JW, et al, eds. Nelson Textbook of Pediatrics. 19th ed. Saunders Elsevier; 2011.Larson RA, Pui CH. Tumor lysis syndrome: Prevention and treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 10, 2019.Latourte A, Bardin T, Richette P. Prophylaxis for acute gout flares after initiation of urate-lowering therapy. Rheumatology (Oxford). 2014;53(11):1920-1926. doi:10.1093/rheumatology/keu157 [PubMed 24758886]Laube R, Paramsothy S, Leong RW. Review of pregnancy in Crohn's disease and ulcerative colitis. Therap Adv Gastroenterol. 2021;14:17562848211016242. doi:10.1177/17562848211016242 [PubMed 34046084]Li X, Zhao Z, Sun SS. Association of human leukocyte antigen variants and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: a meta-analysis. Am J Health Syst Pharm. 2017;74(9):e183-e192. doi:10.2146/ajhp160243 [PubMed 28438823]Lien YH, Logan JL. Cross-reactions between allopurinol and febuxostat. Am J Med. 2017;130(2):e67-e68. doi:10.1016/j.amjmed.2016.08.042 [PubMed 27667702]Lipkin ME, Preminger GM. Demystifying the medical management of nephrolithiasis. Rev Urol. 2011;13(1):34-38. [PubMed 21826126]Mitra S, Cohen RA. Medical management of uric acid stones. In: Han H, Mutter WP, Nasser S, eds. Nutritional and Medical Management of Kidney Stones. Springer International Publishing; 2019.National Institute for Health and Care Excellence. Drug allergy: diagnosis and management of drug allergy in adults, children and young people. https://www.nice.org.uk/guidance/cg183. Published September 2014. Accessed November 19, 2020.Ng CY, Yeh YT, Wang CW, et al. Impact of the HLA-B(*)58:01 allele and renal impairment on allopurinol-induced cutaneous adverse reactions. J Invest Dermatol. 2016;136(7):1373-1381. doi:10.1016/j.jid.2016.02.808 [PubMed 26996548]Park HJ, Yun J, Kang DY, et al. Unique clinical characteristics and prognosis of allopurinol-induced severe cutaneous adverse reactions. J Allergy Clin Immunol Pract. 2019;7(8):2739-2749.e3. doi:10.1016/j.jaip.2019.05.047 [PubMed 31201937]Patel AV, Gaffo AL. Managing gout in women: current perspectives. J Inflamm Res. 2022;15:1591-1598. doi:10.2147/JIR.S284759 [PubMed 35264868]Perez-Ruiz F. Pharmacologic urate-lowering therapy and treatment of tophi in patients with gout. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 19, 2022.Polimeni G, Cardillo R, Garaffo E, et al. Allopurinol-induced Sweet's syndrome. Int J Immunopathol Pharmacol. 2016;29(2):329-332. doi:10.1177/0394632015599705 [PubMed 26684631]Qaseem A, Harris RP, Forciea MA; Clinical Guidelines Committee of the American College of Physicians. Management of acute and recurrent gout: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2017;166(1):58-68. doi:10.7326/M16-0570 [PubMed 27802508]Quach C, Galen BT. HLA-B*5801 testing to prevent allopurinol hypersensitivity syndrome: a teachable moment. JAMA Intern Med. 2018;178(9):1260-1261. doi:10.1001/jamainternmed.2018.3556 [PubMed 30083702]Ramasamy SN, Korb-Wells CS, Kannangara DR, et al. Allopurinol hypersensitivity: a systematic review of all published cases, 1950-2012. Drug Saf. 2013;36(10):953-980. doi:10.1007/s40264-013-0084-0 [PubMed 23873481]Raper R, Ibels L, Lauer C, Barnes P, Lunzer M. Fulminant hepatic failure due to allopurinol. Aust N Z J Med. 1984;14(1):63-65. doi:10.1111/j.1445-5994.1984.tb03591.x [PubMed 6590011]Refer to manufacturer's labeling.Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2017;76(1):29-42. doi:10.1136/annrheumdis-2016-209707 [PubMed 27457514]Saito Y, Stamp LK, Caudle KE, et al; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for human leukocyte antigen B (HLA-B) genotype and allopurinol dosing: 2015 update. Clin Pharmacol Ther. 2016;99(1):36-37. doi:10.1002/cpt.161 [PubMed 26094938]Santos-Victoriano M, Brouhard BH, Cunningham RJ 3rd. Renal stone disease in children. Clin Pediatr (Phila). 1998;37(10):583-599. [PubMed 9793728]Schrijvers R, Gilissen L, Chiriac AM, Demoly P. Pathogenesis and diagnosis of delayed-type drug hypersensitivity reactions, from bedside to bench and back. Clin Transl Allergy. 2015;5:31. doi:10.1186/s13601-015-0073-8 [PubMed 26339470]Serikawa T, Abe T, Minamikawa T, et al. A case report of fatal tumor lysis syndrome after chemotherapy in a pregnant patient with Burkitt's lymphoma. J Obstet Gynaecol Res. 2011;37(8):1141-1144. doi:10.1111/j.1447-0756.2010.01485.x [PubMed 21481095]Shankar P, Aish L, Hassoun H. Allopurinol-induced pure red cell aplasia. Am J Hematol. 2003;73(1):69. doi:10.1002/ajh.10315 [PubMed 12701126]Sheikh M, Nelson-Piercy C, Duley J, Florin T, Ansari A. Successful pregnancies with thiopurine-allopurinol co-therapy for inflammatory bowel disease. J Crohns Colitis. 2015;9(8):680-684. doi:10.1093/ecco-jcc/jjv072 [PubMed 25939351]Simsek M, Opperman RCM, Mulder CJJ, Lambalk CB, de Boer NKH. The teratogenicity of allopurinol: a comprehensive review of animal and human studies. Reprod Toxicol. 2018;81:180-187. doi:10.1016/j.reprotox.2018.08.012 [PubMed 30125681]Stamp LK, Barclay ML. How to prevent allopurinol hypersensitivity reactions? Rheumatology (Oxford). 2018;57(suppl 1):i35-i41. doi:10.1093/rheumatology/kex422 [PubMed 29272508]Stamp LK, Day RO, Yun J. Allopurinol hypersensitivity: investigating the cause and minimizing the risk. Nat Rev Rheumatol. 2016;12(4):235-242. doi: 10.1038/nrrheum.2015.132. Erratum in: Nat Rev Rheumatol. 2016;12(4):i. [PubMed 26416594]Stamp LK, Taylor WJ, Jones PB, et al. Starting dose is a risk factor for allopurinol hypersensitivity syndrome: a proposed safe starting dose of allopurinol. Arthritis Rheum. 2012;64(8):2529-2536. doi:10.1002/art.34488 [PubMed 22488501]Strilchuk L, Fogacci F, Cicero AF. Safety and tolerability of available urate-lowering drugs: a critical review. Expert Opin Drug Saf. 2019;18(4):261-271. doi:10.1080/14740338.2019.1594771 [PubMed 30915866]Torrance HL, Benders MJ, Derks JB, et al. Maternal allopurinol during fetal hypoxia lowers cord blood levels of the brain injury marker S-100B. Pediatrics. 2009;124(1):350-357. doi:10.1542/peds.2008-2228 [PubMed 19564319]Torres RJ, Prior C, Puig JG. Efficacy and safety of allopurinol in patients with hypoxanthine-guanine phosphoribosyltransferase deficiency. Metabolism. 2007a;56(9):1179-1186. [PubMed 17697859]Torres RJ, Puig JG. Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome. Orphanet J Rare Dis. 2007b;2:48. [PubMed 18067674]van Veen TR, Haeri S. Gout in pregnancy: a case report and review of the literature. Gynecol Obstet Invest. 2015;79(4):217-221. doi:10.1159/000369999 [PubMed 25660596]Vargas-Santos AB, Neogi T. Management of gout and hyperuricemia in CKD. Am J Kidney Dis. 2017;70(3):422-439. doi: 10.1053/j.ajkd.2017.01.055 [PubMed 28456346]Wang CW, Dao RL, Chung WH. Immunopathogenesis and risk factors for allopurinol severe cutaneous adverse reactions. Curr Opin Allergy Clin Immunol. 2016;16(4):339-345. doi:10.1097/ACI.0000000000000286 [PubMed 27362322]World Health Organization. Breastfeeding and maternal medication: recommendations for drugs in the eleventh WHO model list of essential drugs. 2002. https://apps.who.int/iris/handle/10665/62435Wortmann RL, Macdonald PA, Hunt B, Jackson RL. Effect of prophylaxis on gout flares after the initiation of urate-lowering therapy: analysis of data from three phase III trials. Clin Ther. 2010;32(14):2386-2397. doi:10.1016/j.clinthera.2011.01.008 [PubMed 21353107]Wright DF, Doogue MP, Barclay ML, et al. A population pharmaco*kinetic model to predict oxypurinol exposure in patients on haemodialysis. Eur J Clin Pharmacol. 2017;73(1):71-78. doi:10.1007/s00228-016-2133-y [PubMed 27683090]Yang CY, Chen CH, Deng ST, et al. Allopurinol use and risk of fatal hypersensitivity reactions: a nationwide population-based study in Taiwan. JAMA Intern Med. 2015;175(9):1550-1557. doi:10.1001/jamainternmed.2015.3536 [PubMed 26193384]Yeo E, Palmer SC, Chapman PT, Frampton C, Stamp LK. Serum urate levels and therapy in adults treated with long-term dialysis: a retrospective cross-sectional study. Intern Med J. 2019;49(7):838-842. doi:10.1111/imj.14163 [PubMed 30426652]Yokose C, Lu N, Xie H, et al. Heart disease and the risk of allopurinol-associated severe cutaneous adverse reactions: a general population-based cohort study. CMAJ. 2019;191(39):E1070-E1077. doi:10.1503/cmaj.190339 [PubMed 31570545]Zyloprim (allopurinol) tablets [prescribing information]. East Brunswick, NJ: Casper Pharma LLC; August 2022.Zyloprim (allopurinol) [product monograph]. Vaughan, Ontario, Canada: AA Pharma Inc; September 2021.Topic 13339 Version 438.0

CloseOndansetron: Drug informationOndansetron: Drug information(For additional information see "Ondansetron: Patient drug information" and see "Ondansetron: Pediatric drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USZofran;Zuplenz [DSC]Brand Names: CanadaACCEL-Ondansetron;APO-Ondansetron;ATHENA-Ondansetron ODT;AURO-Ondansetron;Auro-Ondansetron ODT;CCP-Ondansetron;JAMP Ondansetron;JAMP-Ondansetron;Mar-Ondansetron;MAR-Ondansetron ODT;MINT-Ondansetron;MINT-Ondansetron ODT;MYLAN-Ondansetron;NAT-Ondansetron;Ondansetron ODT;Ondissolve ODF;PMS-Ondansetron;PMS-Ondansetron ODT;SANDOZ Ondansetron;TEVA Ondansetron;VAN-Ondansetron [DSC];Zofran;Zofran ODTPharmacologic CategoryAntiemetic;Selective 5-HT3 Receptor AntagonistDosing: AdultNote: Zuplenz has been discontinued in the United States for >1 year. Single IV doses >16 mg are no longer recommended due to the potential for QT prolongation (Ref). Avoid use in patients with congenital long-QT syndrome.Carcinoid syndrome-associated diarrhea, severe, refractoryCarcinoid syndrome-associated diarrhea, severe, refractory (alternative agent) (off-label use): Based on limited data (case reports):Oral: 8 mg 3 times daily (Wymenga 1998) or 8 mg twice daily for 3 days, followed by a maintenance dose of 4 to 8 mg/day for 4 to 12 weeks (Ref).IV: 4 to 8 mg every 8 hours (Ref).Chemotherapy-induced nausea and vomiting, preventionChemotherapy-induced nausea and vomiting, prevention:Single-day IV chemotherapy regimens:Highly emetogenic chemotherapy (>90% risk of emesis [eg, cisplatin, breast cancer regimens that include an anthracycline combined with cyclophosphamide]):Day of chemotherapy: Administer prior to chemotherapy and in combination with a neurokinin 1 (NK1) receptor antagonist, dexamethasone, and olanzapine (Ref).IV: 8 mg or 0.15 mg/kg as a single dose (Ref). Maximum: 16 mg/dose (Ref).Oral:Tablet formulations and oral solution: 8 mg twice daily for 2 doses with the first dose administered prior to chemotherapy administration (Ref) or 24 mg as a single dose (Ref).Oral soluble film: 24 mg (three 8 mg doses given together) as a single dose (Ref).Post–chemotherapy days: 5-HT3 receptor antagonist use is not necessary (other components of the antiemetic regimen are administered) (Ref).Moderately emetogenic chemotherapy (30% to 90% risk of emesis): Carboplatin-based regimens:Day of chemotherapy: Administer prior to chemotherapy and in combination with an NK1 receptor antagonist and dexamethasone (Ref).IV: 8 mg or 0.15 mg/kg as a single dose (Ref). Maximum: 16 mg/dose (Ref).Oral: 8 mg twice daily for 2 doses with the first dose administered prior to chemotherapy administration (Ref).Post–chemotherapy days: 5-HT3 receptor antagonist use is not necessary (other components of the antiemetic regimen may be administered) (Ref).Moderately emetogenic chemotherapy (30% to 90% risk of emesis): Non-carboplatin-based regimens (alternative agent): Note: ASCO guidelines and MASCC/ESMO guidelines do not state a preference for which 5-HT3 receptor antagonist should be used in this setting; however, palonosetron may be preferred (Ref).Day of chemotherapy: Administer prior to chemotherapy and in combination with dexamethasone (Ref).IV: 8 mg or 0.15 mg/kg as a single dose (Ref). Maximum: 16 mg/dose (Ref).Oral: 8 mg twice daily for 2 doses with the first dose administered prior to chemotherapy administration (Ref).Post–chemotherapy days: 5-HT3 receptor antagonist use is not necessary (other components of the antiemetic regimen may be administered) (Ref); however, if a first-generation 5-HT3 receptor antagonist (eg, ondansetron, granisetron) was used on day 1 of chemotherapy rather than palonosetron, the first-generation 5-HT3 receptor antagonist may be continued for postchemotherapy emetic prophylaxis on days 2 and 3 (Ref).Low emetogenic risk (10% to 30% risk of emesis):Note: Single-agent ondansetron is an option for prophylaxis (Ref).Day of chemotherapy: IV: 8 mg as a single dose prior to chemotherapy (Ref).Oral (off-label): 8 mg as a single dose prior to chemotherapy (Ref).Post–chemotherapy days: Prophylaxis is not necessary on subsequent days (Ref).Minimal emetogenic risk (<10% risk of emesis): Routine antiemetic prophylaxis is not generally necessary (Ref).High-dose chemotherapy with stem or bone marrow transplant: Day of chemotherapy: Administer prior to chemotherapy and in combination with a neurokinin 1 (NK1) receptor antagonist, dexamethasone, with or without olanzapine (Ref).IV: 8 mg or 0.15 mg/kg as a single dose (Ref). Maximum: 16 mg/dose (Ref).Oral: 24 mg as a single dose (Ref).Oral chemotherapy agents:High/moderate emetogenic risk oral agent (≥30% risk of emesis): Oral: 8 to 16 mg/day administered before chemotherapy and continued daily (Ref).Low/minimal emetogenic risk oral agent (<30% risk of emesis): Oral: 8 to 16 mg/day on an as-needed basis only (Ref).Gastroparesis, symptomatic treatment of nausea and vomitingGastroparesis, symptomatic treatment of nausea and vomiting (alternative agent) (off-label use): Note: For patients with persistent symptoms refractory to prokinetic therapy. No data available; recommendations for use and dose are based on expert opinion.Oral: 4 to 8 mg 3 times daily (Ref).Nausea and/or vomiting, acute, severeNausea and/or vomiting, acute, severe (off-label use): Note: Use has primarily been evaluated in patients with undifferentiated nausea/vomiting presenting to the emergency department; however, may also use for nausea/vomiting due to viral gastroenteritis, acute mountain sickness, and a variety of other medical conditions associated with severe, self-limiting acute nausea/vomiting (Ref).Oral, IV, IM: 4 mg as a single dose (Ref). Note: For parenteral therapy, IV administration is preferred over IM when possible (Ref).Prevention of vomiting (and associated increase in intraocular pressure) in patients with eye trauma: IV: 4 to 8 mg as a single dose (Ref).Postoperative nausea and vomiting, preventionPostoperative nausea and vomiting, prevention:Moderate- to high-risk patients: Note: In patients at moderate risk, may combine ondansetron with other prophylactic interventions (eg, another antiemetic agent from a different pharmacologic class, modification of anesthetic technique, acupuncture); in patients at high risk, combine 3 or more interventions (Ref).Usual dose: IV: 4 mg as a single dose at the end of surgery (Ref).Alternative strategy: Oral (oral disintegrating tablet or oral soluble film): 8 mg as a single dose given 30 to 60 minutes prior to surgery (Ref).Low-risk patients:Although prophylaxis is not always indicated in low-risk patients, consensus guidelines acknowledge that some experts may administer an antiemetic in these patients; however, clinicians are also advised that this strategy comes with the potentially unnecessary risk of rare adverse effects (Ref). If ondansetron is given, the dosing is the same as for moderate- to high-risk patients.Postdischarge management in high-risk patients: Limited data available; dosage regimen studied in a single clinical trial: Oral (oral disintegrating tablet or oral soluble film): 8 mg to be taken on discharge and in the morning of postoperative days 1 and 2 (Ref).Postoperative nausea and vomiting, treatment or rescue therapyPostoperative nausea and vomiting, treatment or rescue therapy (off-label use): IV: 4 mg as a single dose when a prophylactic agent was not utilized (treatment) or following failure of an agent utilized as prophylaxis (rescue therapy) (Ref). Note: Rescue therapy should always include an antiemetic from a different class than the one used for prophylaxis, unless a potentially inadequate dose was initially administered or the effect of the first drug has worn off (>6 hours since initial dose for most 5-HT3 receptor antagonists) (Ref). However, some experts do not recommend repeat administration of a 5-HT3 antagonist unless triple therapy has been used for prophylaxis and no alternatives are available for rescue that were not used for prophylaxis (Ref).Pregnancy-associated nausea and vomiting, severe or refractoryPregnancy-associated nausea and vomiting, severe or refractory (off-label use): Note: May be considered for adjunctive treatment of nausea and vomiting when symptoms persist following initial pharmacologic therapy (Ref).Patients without hypovolemia:Oral, IV (bolus): 4 mg every 8 hours, as needed, added to current treatment regimen (Ref). If necessary, some experts increase to a maximum of 8 mg/dose (Ref).Patients with hypovolemia:Note: For patients with persistent symptoms despite intravenous fluid replacement:IV: 8 mg administered over 15 minutes every 12 hours, added to current treatment regimen (Ref). Some experts use 4 to 8 mg administered as an IV bolus every 8 hours until stabilization (Ref).Radiation therapy-associated nausea and vomiting, preventionRadiation therapy-associated nausea and vomiting, prevention: High-emetogenic risk radiation therapy (total body irradiation): Radiation day(s):IV (off-label): 8 mg or 0.15 mg/kg (maximum: 16 mg/dose [manufacturer’s labeling]) once daily or twice daily prior to each fraction of radiation; administer in combination with dexamethasone (Ref).Oral: 8 mg once daily or twice daily administered 1 to 2 hours prior to each fraction of radiation; administer in combination with dexamethasone (Ref) or, in one clinical trial of 4 days of hyperfractionated total body irradiation, 8 mg (without dexamethasone) was administered 1.5 hours prior to every fraction of radiation (3 times daily for the first 3 days and twice daily on day 4) (Ref).Post–radiation days: IV (off-label), Oral: The appropriate duration of therapy following radiotherapy days is not well defined; ASCO guidelines recommend continuing ondansetron once daily or twice daily on the day after each day of radiation (Ref).Moderate-emetogenic risk radiation therapy (upper abdomen, craniospinal irradiation) (off-label use): Radiation day(s):IV (off-label): 8 mg or 0.15 mg/kg (maximum: 16 mg/dose [manufacturer’s labeling]) once daily or twice daily prior to each fraction of radiation; may administer with or without dexamethasone before the first 5 fractions (Ref).Oral: 8 mg once daily or twice daily administered 1 to 2 hours prior to each fraction of radiation; may administer with or without dexamethasone before the first 5 fractions (Ref) or, in clinical trials involving upper abdomen radiation (high-dose single exposure or multiple-day fractionated course), 8 mg 3 times daily (without dexamethasone) has been given; doses were administered 1 to 2 hours prior to radiation therapy (Ref).Low- (brain, head and neck, thorax, pelvis) to minimal- (extremities, breast) emetogenic risk radiation therapy:Routine prophylaxis not recommended; however, may use as rescue therapy using the following dosing with consideration of using prophylactically for the remainder of radiation therapy (Ref).IV: 8 mg or 0.15 mg/kg (Ref) (maximum: 16 mg/dose (Ref)).Oral: 8 mg (Ref).Vertigo-associated nausea and vomitingVertigo-associated nausea and vomiting (alternative agent) (off-label use):IV (preferred), IM: 4 to 8 mg once for acute symptoms (Ref).Oral: 4 mg every 8 to 12 hours as needed (Ref).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultThe renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.Altered kidney function: IV, Oral: No dose adjustments likely to be necessary, as clearance by the kidney accounts for only 5% of total clearance (Roila 1995; manufacturer’s labeling). Unlikely to be significantly dialyzed due to relatively high volume of distribution and plasma protein binding (Ref).Dosing: Hepatic Impairment: AdultMild to moderate impairment: No dosage adjustment necessary.Severe impairment (Child-Pugh class C):IV: Day 1: Maximum daily dose: 8 mg; however, according to the manufacturer, there is no experience beyond first-day administration (has not been studied beyond day 1)Oral: Maximum daily dose: 8 mgDosing: Pediatric(For additional information see "Ondansetron: Pediatric drug information")Note: Zuplenz oral film has been discontinued in the United States for >1 year.Chemotherapy-induced nausea and vomiting, preventionChemotherapy-induced nausea and vomiting, prevention: Note: Use in combination with or without dexamethasone and aprepitant or fosaprepitant depending upon patient age, chemotherapy emetogenic potential, and drug-interaction profile (refer to specific protocols or guidelines) (Ref).Guideline dosing:Highly emetogenic chemotherapy: Infants, Children, and Adolescents: IV, Oral: 0.15 mg/kg/dose (5 mg/m2/dose); administer first dose before the start of chemotherapy and then every 8 hours (Ref); usual reported maximum dose: 8 mg/dose (Ref).Moderately emetogenic chemotherapy: Infants, Children, and Adolescents: IV, Oral: 0.15 mg/kg/dose (5 mg/m2/dose); maximum dose: 8 mg/dose; administer first dose before the start of chemotherapy with subsequent doses every 12 hours (Ref).Low emetogenic chemotherapy: Infants, Children, and Adolescents: IV, Oral: 0.3 mg/kg/dose once (10 mg/m2/dose); maximum dose: 16 mg/dose; administered 30 minutes before the start of chemotherapy (Ref).Manufacturer's labeling:IV: Emetogenic chemotherapy: Infants, Children, and Adolescents (limited data available for infants <6 months): IV: 0.15 mg/kg/dose every 4 hours for a total of 3 doses beginning 30 minutes before the start of chemotherapy (manufacturer's labeling); maximum daily dose: 32 mg/day (Ref).Oral: Moderately emetogenic antineoplastic therapy:Children 4 to 11 years: Oral: 4 mg beginning 30 minutes before chemotherapy; repeat 4 and 8 hours after initial dose, then 4 mg every 8 hours for 1 to 2 days after chemotherapy completed (Ref).Children ≥12 years and Adolescents: Oral: 8 mg beginning 30 minutes before chemotherapy; repeat dose 8 hours after initial dose, then 8 mg every 12 hours for 1 to 2 days after chemotherapy completed (Ref).Single-dose regimen (low, moderate, or highly emetogenic potential): Limited data available; efficacy results variable:Infants, Children, and Adolescents: IV: 0.3 mg/kg/dose once daily; maximum dose: 16 mg/dose (Ref); dosing based on a randomized controlled study comparing a single daily IV dose of 0.3 mg/kg to standard therapy administered every 8 hours in 194 patients ages 0 to 18 years; the single daily dose was shown to be as effective as the multidose regimen in patients ≥7 years of age; however, in patients <7 years of age the every-8-hour dosing provided better control of nausea symptoms (Ref).Cyclic vomiting syndrome; treatment of acute attackCyclic vomiting syndrome (CVS); treatment of acute attack Limited data available; dosing based on case reports and clinical experience:Children >2 years and Adolescents:Low dose: IV: 0.15 mg/kg every 4 hours as needed for up to 3 doses; maximum dose: 16 mg/dose (Ref).High dose: IV: 0.3 to 0.4 mg/kg/dose every 4 to 6 hours; maximum dose: 16 mg/dose (Ref); per manufacturer labeling, should not exceed 3 doses in a 24-hour period.Gastroenteritis, acute; treatmentGastroenteritis, acute; treatment: Note: Routine use of ondansetron is not recommended in most cases of acute gastroenteritis (Ref).IV: Infants and Children: IV: 0.15 or 0.3 mg/kg/dose once; maximum dose: 16 mg/dose (Ref).Oral: Infants ≥6 months and Children ≤10 years, weighing ≥8 kg (Ref):8 to 15 kg: Oral: 2 mg/dose once.>15 to 30 kg: Oral: 4 mg/dose once.>30 kg: Oral: 8 mg/dose once.Postoperative nausea and vomiting; preventionPostoperative nausea and vomiting; prevention: Administer immediately before or following induction of anesthesia, or postoperatively if the patient is symptomatic. Repeat doses given in response to inadequate control of nausea/vomiting from preoperative doses are generally ineffective.Infants and Children:≤40 kg: IV: 0.1 mg/kg/dose as a single dose; maximum dose: 4 mg/dose.>40 kg: IV: 4 mg/dose as a single dose.Adolescents: IM, IV: 4 mg/dose as a single dose.Radiation-induced nausea and vomiting, preventionRadiation-induced nausea and vomiting, prevention: Limited data available:Weight-directed dosing: Infants ≥5 months, Children, and Adolescents: Oral: 0.2 mg/kg/dose (maximum dose: 8 mg/dose) administered every 8 hours throughout total body irradiation (TBI) prior to hematopoietic stem cell transplant (HSCT) (n=68; mean age: 6.7 years; range: 5 months to 20 years); doses were generally rounded to 4 mg/dose in children 4 to 11 years and 8 mg/dose in children ≥12 years and adolescents (Ref).Alternate weight-based dosing: Children and Adolescents: Oral: 0.15 mg/kg/dose administered 3 to 4 times daily throughout TBI (n=33; mean age: 9 years; range: 13 months to 16 years) (Ref).Fixed dose: Note: Derived from rounding weight-based (0.2 mg/kg/dose) doses (Ref).Children 4 to 11 years: Oral: 4 mg every 8 hours throughout TBI prior to HSCT.Children ≥12 years and Adolescents: Oral: 8 mg every 8 hours throughout TBI prior to HSCT.Alternate fixed-dosing: Children ≥9 years and Adolescents: Oral: 8 mg every 12 hours on days of TBI prior to bone marrow transplantation (age range: 9 to 67 years; median age range: 39 to 49 years). Note: Administered in combination with dexamethasone (Ref).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricIV: No dosage adjustment is necessary.Oral: No dosage adjustment is necessary; however, there is no experience for oral ondansetron in renal impairment beyond first-day administration (has not been studied beyond day 1)Dosing: Hepatic Impairment: PediatricThere are no pediatric-specific recommendations; based on experience in adult patients, no adjustment may be necessary for mild to moderate hepatic impairment; for severe impairment, dosing adjustment suggested.Dosing: Older AdultOral: No dosing adjustment required; refer to adult dosing.IV: Single IV doses >16 mg are no longer recommended due to the potential for QT prolongation (Ref). In patients ≥75 years, Canadian recommendations place additional restrictions to limit initial IV doses to ≤8 mg due to this risk (Ref).Dosing: Adjustment for Toxicity: AdultHypersensitivity: Discontinue ondansetron; manage as clinically indicated.Serotonin syndrome: Discontinue ondansetron and initiate supportive management.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.[DSC] = Discontinued productFilm, Oral: Zuplenz: 4 mg (30 ea [DSC]); 8 mg (30 ea [DSC])Solution, Injection, as hydrochloride [strength expressed as base]: Generic: 4 mg/2 mL (2 mL); 40 mg/20 mL (20 mL)Solution, Injection, as hydrochloride [strength expressed as base, preservative free]: Generic: 4 mg/2 mL (2 mL)Solution, Oral, as hydrochloride [strength expressed as base]: Zofran: 4 mg/5 mL (50 mL [DSC])Generic: 4 mg/5 mL (5 mL, 50 mL)Solution Prefilled Syringe, Injection, as hydrochloride: Generic: 4 mg/2 mL (2 mL)Tablet, Oral, as hydrochloride [strength expressed as base]: Zofran: 4 mg, 8 mg [DSC]Generic: 4 mg, 8 mg, 24 mgTablet Disintegrating, Oral: Generic: 4 mg, 8 mgGeneric Equivalent Available: USMay be product dependentDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Film, Oral: Ondissolve ODF: 4 mg (6 ea, 10 ea, 50 ea); 8 mg (6 ea, 10 ea, 50 ea) [contains levomenthol, polyethylene glycol (macrogol), polysorbate 80]Solution, Intravenous: Zofran: 2 mg/mL (2 mL, 4 mL, 20 mL)Generic: 2 mg/mL (2 mL, 4 mL, 5 mL, 20 mL)Solution, Oral, as hydrochloride [strength expressed as base]: Zofran: 4 mg/5 mL (50 mL) [contains alcohol, usp, sodium benzoate]Generic: 4 mg/5 mL (50 mL)Tablet, Oral, as hydrochloride [strength expressed as base]: Zofran: 4 mg, 8 mgGeneric: 4 mg, 8 mgTablet Disintegrating, Oral: Zofran ODT: 4 mg, 8 mg [contains aspartame, methylparaben sodium, propylparaben sodium]Generic: 4 mg, 8 mgProduct AvailabilityZuplenz has been discontinued in the United States for >1 year.Administration: AdultOral: Oral dosage forms should be administered 30 minutes prior to chemotherapy; 1 to 2 hours before radiation; 30 to 60 minutes prior to surgery or induction of anesthesiaOrally disintegrating tablets: Do not remove from blister until needed. Peel backing off the blister, do not attempt to push tablet through the foil. Using dry hands, place tablet on tongue and allow to dissolve. Swallow with saliva (no need to administer with liquids).Oral soluble film: Do not remove from pouch until immediately before use. Using dry hands, place film on top of tongue and allow to dissolve (4 to 20 seconds). Swallow with or without liquid. If using more than one film, each film should be allowed to dissolve completely before administering the next film.IM: Should be administered undiluted.IV:IVPB: Infuse diluted solution over 15 minutesChemotherapy-induced nausea and vomiting: Give first dose 30 minutes prior to beginning chemotherapy.IV push: Prevention of postoperative nausea and vomiting: Single doses may be administered IV injection as undiluted solution over at least 30 seconds but preferably over 2 to 5 minutesAdministration: PediatricOral (all dosage forms): May administer without regard to meals. Administer 30 minutes prior to chemotherapy, 1 to 2 hours prior to radiotherapy, and 1 hour prior to induction of anesthesia.Orally disintegrating tablet (Zofran ODT): Do not remove from blister until needed. Peel backing off the blister; do not push tablet through foil backing. Using dry hands, place tablet on tongue and allow to dissolve; swallow with saliva (no need to administer with liquids).Soluble film (Zuplenz): Do not remove from pouch until immediately before use. Using dry hands, place film on top of tongue and allow to dissolve (4 to 20 seconds). Swallow with or without liquid. If using more than one film, allow each film to dissolve completely before administering the next film.Parenteral:IV:IVPB infusion:Prevention of chemotherapy-induced nausea and vomiting: Infuse over 15 minutes.Cyclic vomiting syndrome: Infuse over 15 to 30 minutes (Ref).IV push: May be administered undiluted IV over 2 to 5 minutes for prevention of PONV.IM: Administer as undiluted injection.Use: Labeled IndicationsCancer chemotherapy-induced nausea and vomiting: IV: Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy (including high-dose cisplatin).Oral:Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy (including cisplatin ≥50 mg/m2).Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.Postoperative nausea and/or vomiting: IV, IM, Oral: Prevention of postoperative nausea and/or vomiting (PONV). If nausea/vomiting occur in a patient who had not received prophylactic ondansetron, IV ondansetron may be administered to prevent further episodes.Limitations of use: Routine prophylaxis for PONV in patients with minimal expectation of nausea and/or vomiting is not recommended, although use is recommended in patients when nausea and vomiting must be avoided in the postoperative period, even if the incidence of PONV is low.Radiotherapy-associated nausea and vomiting: Oral: Prevention of nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen.Use: Off-Label: AdultCarcinoid syndrome-associated diarrhea, severe, refractory; Gastroparesis, symptomatic treatment of nausea and vomiting (alternative agent in patients with persistent symptoms refractory to prokinetic therapy); Nausea and/or vomiting, acute, severe; Postoperative nausea and vomiting, treatment or rescue therapy; Pregnancy-associated nausea and vomiting, severe or refractory; Vertigo-associated nausea and vomitingMedication Safety IssuesSound-alike/look-alike issues: Ondansetron may be confused with dolasetron, granisetron, palonosetron Zofran may be confused with Zantac, ZosynAdverse Reactions (Significant): ConsiderationsConstipationOndansetron may commonly cause constipation (Ref). Rare cases of intestinal obstruction have also been reported (Ref).Mechanism: Likely due to blockade of 5-HT3 gut receptors which results in decreased motility (Ref). May also occur as a result of decreased colonic transit time (Ref) and inhibition of postprandial increase in tone (Ref).Onset: Varied; one reported case of constipation occurred the same day as oral ondansetron administration; intestinal obstruction resulted approximately 2 weeks after continuous twice daily dosing (Ref).Risk factors:• Preexisting liver disease (Ref)HeadacheHeadache is the most reported adverse reaction with ondansetron (Ref). Additional doses and movement (with or without postural changes) have been associated with worsening (Ref). Severe headache has led to discontinuation in reported cases (Ref).Onset: Rapid; severe headache reported to occur within minutes of administration, often lasting minutes to hours. There have been multiple case reports of children experiencing throbbing headaches for several days following ondansetron and chemotherapy (Ref). One patient reported onset of severe headache occurring within 2 hours of the first dose and continued to occur every 12 hours following repeated administration (Ref).Risk factors:• Personal or family history of migraine (Ref)• Concurrent use of propofol and/or fentanyl (Ref)• Higher doses (potential risk factor) (Ref)Hypersensitivity (immediate)Immediate hypersensitivity reactions may occur with ondansetron, including urticaria, angioedema, hypotension, bronchospasm, dyspnea, and anaphylaxis (Ref). Some patients may only present with hypotension, without any accompanying symptoms (Ref). Patients may have more severe reactions on subsequent exposure (Ref).Mechanism: Non-dose-related; immunologic; likely IgE-mediated (Ref); may be the result of direct mast cell stimulation (in some patients without previous exposure) (Ref).Onset: Rapid; immediate hypersensitivity reactions generally occur within 1 hour of administration, but may occur up to 6 hours after exposure (Ref). Reactions usually occur after the first dose during the second or third course of chemotherapy (Ref).Risk factors:• Adults with cancer (Ref); however, a few isolated cases have been reported in children (Ref)• IV route of administration; however, anaphylaxis following sublingual administration has been reported (Ref)• Cross-reaction between serotonin 5-HT3 antagonists has been described in limited case reports (Ref)QT prolongationIncreases in ECG intervals (eg, PR, QRS duration, JT); prolonged QT interval on ECG; and bradycardia have been observed with ondansetron (Ref). Cases of ventricular arrhythmias and torsades de pointes have also been reported. Rare cases of fatalities have occurred even at low doses (Ref).Mechanism: QT prolongation may occur due to HERG K+ channel-blockade (Ref). Suppression of autonomic reflexes may contribute to bradycardia, hypotension, and tachyarrhythmias (Ref).Onset: Rapid; usually occurs 1 to 2 hours after administration (Ref); however, QT prolongation peaks have been observed within ~5 to 15 minutes following administration (Ref). QTc intervals >500 ms have been recorded within 15 minutes after administration (Ref). May persist >2 hours from administered dose (Ref).Risk factors:• IV route of administration (Ref)• Single doses >16 mg IV (Ref); however, risk should be considered even with low IV doses (Ref)• Concomitant medications that prolong the QT interval (Ref)• Females (Ref)• Hypothermia (Ref)• Concomitant volatile anesthetics or cumulative high-dose anthracycline therapy (Ref)• Underlying heart disease including heart failure or acute coronary syndromes (Ref)• Electrolyte abnormalities (eg, hypokalemia, hypomagnesemia) (Ref)• History of QT prolongation, bradycardia, tachycardia, or cardiac rhythm disorders (especially ventricular arrhythmia) (Ref)• Patients receiving ondansetron following anesthesia, while in the intensive care unit, or during hospital admission (Ref)Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidence reported in adult patients unless otherwise specified.>10%:Gastrointestinal: Constipation (9% to 11%)Ondansetron: Adverse Reaction: ConstipationDrug (Ondansetron)Placebo DoseDosage FormIndicationNumber of Patients (Ondansetron)Number of Patients (Placebo)9%0.4%8 mg twice dailyOralChemotherapy-induced nausea and vomiting24226211%N/AN/AInjectionN/AN/AN/ANervous system: Fatigue (oral: ≤13%), headache (9% to 24%), malaise (oral: ≤13%)Ondansetron: Adverse Reaction: HeadacheDrug (Ondansetron)Comparator (Metoclopramide)Placebo DoseDosage FormIndicationNumber of Patients (Ondansetron)Number of Patients (Metoclopramide)Number of Patients (Placebo)24%N/A13%8 mg twice dailyOralChemotherapy-induced nausea and vomiting242N/A26217%7%15%0.15 mg/kg x 3InjectionChemotherapy-induced nausea and vomiting4191563417%N/A14%4 mg single doseIVPostoperative nausea and vomiting547N/A5479%N/A5%16 mg single doseOralPostoperative nausea and vomiting550N/A5311% to 10%:Dermatologic: Pruritus (2% to 5%), skin rash (1%)Gastrointestinal: Diarrhea (oral: 6%; IV: children 1 to 24 months of age: 2%)Genitourinary: Gynecologic disease (oral: 7%), urinary retention (oral: 5%)Hepatic: Increased serum alanine aminotransferase (>2 times ULN: 1% to 5%; transient), increased serum aspartate aminotransferase (>2 times ULN: 1% to 5%; transient)Hypersensitivity: Anaphylaxis (<2%) (Fernando 2009)Local: Injection site reaction (4%; includes burning sensation at injection site, erythema at injection site, injection site pain)Nervous system: Agitation (oral: ≤6%), anxiety (oral: ≤6%), dizziness (7%), drowsiness (IV: ≤8%), paresthesia (IV: 2%), sedated state (IV: ≤8%), sensation of cold (IV: 2%)Respiratory: Bronchospasm (<2%), hypoxia (oral: 9%)Miscellaneous: Fever (2% to 8%)<1%:Cardiovascular: HypotensionNervous system: Extrapyramidal reaction (Ritter 2003; Sprung 2003)Frequency not defined:Cardiovascular: Angina pectoris, peripheral vascular disease, tachycardiaEndocrine & metabolic: HypokalemiaNervous system: Tonic clonic epilepsyPostmarketing:Cardiovascular: Atrial fibrillation (Havrilla 2009), bradycardia (Afonso 2009; Rapp 2015), depression of ST segment on ECG, flushing, ischemic heart disease (most commonly due to coronary artery spasm and may occur with oral or IV [predominantly IV]; occurred immediately after IV administration and resolved with treatment), palpitations, prolonged QT interval on ECG (Ganjare 2013; Moffett 2016), second degree atrioventricular block, supraventricular tachycardia, syncope, torsades de pointes (Lee 2017; Patel 2019), ventricular premature contractions, ventricular tachycardiaDermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis (Saraogi 2012), urticaria (Bousquet 2005)Gastrointestinal: Hiccups, intestinal obstruction (Cohen 2014)Hematologic & oncologic: Positive lymphocyte transformation testHepatic: Hepatic failureHypersensitivity: Angioedema, fixed drug eruption (Maitra 2017), hypersensitivity reaction (Garcia Nunez 2015; Leung 2013), nonimmune anaphylaxisNervous system: Dystonic reaction (Diaz-Parlet 2015), serotonin syndrome (George 2008)Neuromuscular & skeletal: LaryngospasmOphthalmic: Accommodation disturbance, oculogyric crisis (Macachor 2014), transient blindness (lasted ≤48 hours) (Cherian 2005), transient blurred vision (following infusion)Respiratory: Dyspnea, laryngeal edema, stridorContraindicationsHypersensitivity to ondansetron or any component of the formulation; concomitant use with apomorphineWarnings/PrecautionsConcerns related to adverse effects:• Serotonin syndrome: Serotonin syndrome (SS) has been reported with 5-HT3 receptor antagonists, predominantly when used in combination with other serotonergic agents (eg, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and/or methylene blue). Some of the cases have been fatal. The majority of serotonin syndrome reports due to 5-HT3 receptor antagonist have occurred in a postanesthesia setting or in an infusion center. SS has also been reported following overdose of ondansetron. Signs/symptoms of SS include mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile BP, diaphoresis, dizziness, flushing, hyperthermia); neuromuscular changes (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures.Dosage form specific issues:• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.• Phenylalanine: Orally disintegrating tablets contain phenylalanine.Other warnings/precautions:• Chemotherapy-associated emesis: Antiemetics are most effective when used prophylactically (MASCC/ESMO [Roila 2016]). If emesis occurs despite optimal antiemetic prophylaxis, re-evaluate emetic risk, disease status, concurrent morbidities and current medications to assure antiemetic regimen is optimized (ASCO [Hesketh 2020]).Metabolism/Transport EffectsSubstrate of CYP1A2 (minor), CYP2C9 (minor), CYP2D6 (minor), CYP2E1 (minor), CYP3A4 (minor), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potentialDrug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Amiodarone: May enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modificationAmisulpride (Oral): May enhance the QTc-prolonging effect of Ondansetron. Risk C: Monitor therapyApomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine.Risk X: Avoid combinationCYP3A4 Inducers (Strong): May decrease the serum concentration of Ondansetron. Risk C: Monitor therapyDabrafenib: Ondansetron may enhance the QTc-prolonging effect of Dabrafenib.Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyDomperidone: May enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modificationFluorouracil Products: Ondansetron may enhance the QTc-prolonging effect of Fluorouracil Products.Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyHaloperidol: Ondansetron may enhance the QTc-prolonging effect of Haloperidol.Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyMetFORMIN: Ondansetron may increase the serum concentration of MetFORMIN.Risk C: Monitor therapyPanobinostat: Ondansetron may enhance the arrhythmogenic effect of Panobinostat.Risk C: Monitor therapyPentamidine (Systemic): May enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyPimozide: May enhance the QTc-prolonging effect of Ondansetron. Risk X: Avoid combinationQT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modificationQT-prolonging Antidepressants (Moderate Risk): Ondansetron may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Ondansetron may enhance the serotonergic effect of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome.Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome when these agents are combined. Patients with additional risk factors for QTc prolongation or serotonin syndrome may be at even higher risk. Risk C: Monitor therapyQT-prolonging Antipsychotics (Moderate Risk): Ondansetron may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk).Management: Monitor for QTc interval prolongation, ventricular arrhythmias, including torsades de pointes, when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyQT-prolonging Class IA Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modificationQT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyQT-prolonging Class III Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modificationQT-Prolonging Inhalational Anesthetics (Moderate Risk): Ondansetron may enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk).Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyQT-prolonging Kinase Inhibitors (Moderate Risk): Ondansetron may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk).Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyQT-prolonging Miscellaneous Agents (Moderate Risk): May enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyQT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): Ondansetron may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk).Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyQT-prolonging Quinolone Antibiotics (Moderate Risk): Ondansetron may enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk).Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyQT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapySerotonergic Agents (High Risk): Ondansetron may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome.Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapyTapentadol: Ondansetron may diminish the analgesic effect of Tapentadol.Risk C: Monitor therapyTraMADol: Ondansetron may enhance the serotonergic effect of TraMADol. This could result in serotonin syndrome. Ondansetron may diminish the therapeutic effect of TraMADol.Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and diminished tramadol efficacy when these agents are combined. Risk C: Monitor therapyFood InteractionsTablet: Food slightly increases the extent of absorption. Management: Administer without regard to meals.Pregnancy ConsiderationsOndansetron crosses the placenta (Elkomy 2014; Siu 2006).Ondansetron can be detected in fetal tissue (Siu 2006). The risk of developing a major congenital malformation following first trimester exposure is under study. Risks related to specific birth defects (eg, cardiac anomalies, oral clefts) requires confirmation; available human data are conflicting (ACOG 2018; Dormuth 2021; Kaplan 2019; Lemon 2020; Lavecchia 2018; Picot 2020). Clearance is decreased immediately after birth in neonates exposed to ondansetron in utero (Elkomy 2014).Due to pregnancy-induced physiologic changes, clearance of ondansetron may increase as pregnancy progresses (Lemon 2016). Dose adjustment is not needed when administered for the prevention of nausea and vomiting associated with cesarean delivery (Elkomy 2014).Ondansetron may be considered for the treatment of severe or refractory nausea and vomiting of pregnancy (NVP) when preferred agents have failed (ACOG 2018; Campbell 2016). Until additional information related to fetal safety is available, current guidelines suggest use prior to 10 weeks gestation be individualized (ACOG 2018). Dose-dependent QT-interval prolongation can occur with use; therefore, ECG monitoring is recommended in patients with risk factors for arrhythmia (ACOG 2018); this may include patients with electrolyte abnormalities associated with some cases of NVP (Koren 2012).Ondansetron may be considered as part of a multimodal approach to prevent nausea and vomiting associated with cesarean delivery. A combination of ≥2 antiemetics with different mechanisms of action is recommended to treat intraoperative and postoperative nausea and vomiting (Bollag 2021; Griffiths 2012; Habib 2013; Jetling 2017; Macones 2019; Zhou 2018).An international consensus panel recommends that 5-HT3 antagonists (including ondansetron) can be used when necessary in pregnant patients receiving chemotherapy for the treatment of gynecologic cancers (Amant 2019).Breastfeeding ConsiderationsIt is not known if ondansetron is present in breast milk.According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the patient.Dietary ConsiderationsSome products may contain phenylalanine.Monitoring ParametersECG if applicable (eg, high-risk or elderly patients, concurrent use of other medications known to prolong QT interval, electrolyte abnormalities [hypokalemia or hypomagnesemia], heart failure, bradyarrhythmias, and cumulative high-dose anthracycline therapy); serum potassium and magnesium levels. Monitor for signs/symptoms of serotonin syndrome and hypersensitivity; monitor for decreased bowel activity (particularly in patients at risk for bowel obstruction). Monitor for signs/symptoms of myocardial ischemia.Mechanism of ActionOndansetron is a selective 5-HT3-receptor antagonist which blocks serotonin, both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zonePharmaco*kineticsOnset of action: ~30 minutesAbsorption: Oral: 100%; nonlinear absorption occurs with increasing oral doses; Zofran ODT tablets are bioequivalent to Zofran tablets; absorption does not occur via oral mucosad*stribution: Vd:Infants and Children: Surgical patients:1 to 4 months: 3.5 L/kg5 to 24 months: 2.3 L/kg3 to 12 years: 1.65 L/kgChildren and Adolescents: Cancer patients: 4 to 18 years: 1.9 L/kgAdults: 1.9 L/kgProtein binding, plasma: 70% to 76%Metabolism: Extensively hepatic via hydroxylation, followed by glucuronide or sulfate conjugation; CYP1A2, CYP2D6, and CYP3A4 substrate; some demethylation occursBioavailability: Oral: 50% to 70% due to some first-pass metabolism; in cancer patients (adults), 85% to 87% bioavailability possibly related to changes in metabolismHalf-life elimination:Children: Cancer patients: Children and Adolescents: 4 to 18 years: 2.8 hours; Surgical patients: Infants 1 to 4 months: 6.7 hours; Infants and Children 5 months to 12 years: 2.9 hoursAdults: 3 to 6 hours; Mild-to-moderate hepatic impairment (Child-Pugh classes A and B): 12 hours; Severe hepatic impairment (Child-Pugh class C): 20 hoursTime to peak: Oral: ~2 hours; Oral soluble film: ~1 hourExcretion: Urine (44% to 60% as metabolites, ~5% as unchanged drug); feces (~25%)Clearance:Cancer patients: Children and Adolescents 4 to 18 years: 0.599 L/kg/hourSurgical patients: Infants and Children: 1 to 4 months: 0.401 L/kg/hour; 5 to 24 months: 0.581 L/kg/hour; 3 to 12 years: 0.439 L/kg/hourAdult (normal): 19 to 40 years: 0.381 L/kg/hour; 61 to 74 years: 0.319 L/kg/hour; >75 years: 0.262 L/kg/hourPharmaco*kinetics: Additional ConsiderationsAltered kidney function: Mean plasma clearance is reduced by 41% (IV) and 50% (oral) in patients with severe renal impairment (CrCl <30 mL/minute).Hepatic function impairment: In patients with mild to moderate impairment, clearance is reduced 2-fold and the mean half-life is increased to 11.6 hours (compared to 5.7 hours in subjects with normal hepatic function). Clearance is reduced 2- to 3-fold and the apparent Vd is increased, and the half-life is increased to 20 hours in patients with severe hepatic impairment (Child-Pugh class C).Older adult: In elderly patients >75 years of age, there is a reduction in clearance and an increase in elimination half-life.Sex: The extent and rate of absorption is greater in women than in men. There is slower clearance, a smaller volume of distribution, and higher bioavailability in women.Pricing: USSolution (Ondansetron HCl Injection)4 mg/2 mL (per mL): $0.28 - $1.3540 mg/20 mL (per mL): $0.30 - $1.25Solution (Ondansetron HCl Oral)4 mg/5 mL (per mL): $4.78 - $6.00Solution Prefilled Syringe (Ondansetron HCl Injection)4 mg/2 mL (per mL): $1.11Tablet, orally-disintegrating (Ondansetron Oral)4 mg (per each): $22.25 - $23.118 mg (per each): $36.66 - $38.50Tablets (Ondansetron HCl Oral)4 mg (per each): $0.54 - $24.898 mg (per each): $0.64 - $41.5324 mg (per each): $106.51Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalAntivon (CR, DO, GT, HN, NI, PA, SV);Apulset (BD);Avessa (LU);Avessaron (BE);Cedantron (ID);Cetron (AR);Danac (MX);Danset (EG);Dantron (TH, ZA);Emeset (IN, LK, RO);Emeton (UA);Emetron (HU);Emiset (BD);Emistop (ZA, ZW);Emizof (IE);Emodan (PH);Enset (PH);Finaber (PY);Frazon (ID);Glotron (ID);Invomit (ID);Izofran (CL, UY);Krindor (CR, DO, GT, HN, NI, PA, SV);Lartron (MX);Mefoz (ID);Modifical (CO, EC);Nalisen (CR, DO, GT, HN, NI, PA, SV);Narfoz (ID);Nausedron (BR);Odnatron (IL);Ofran (LK);Ondak (CO);Ondan (EG);Ondanaccord (NZ);Ondant (KR);Ondantor (HR);Ondavell (ID, MY, PH, SG, TH);Ondawi (LK);Ondran (IE);Onetic (ID);Onrex (NZ);Onsat (BD);Onset-8 (PH);Onsetron (KR);Onsett (TZ, ZW);Onsia (TH);Onzet (PH);Onzod (TW);Osetron (AU, BD, RO);Periset (BD);Setofilm (ES, GB);Setron (BH);Setronax (HK, MY, SG, VN);Trondamet (HK);Vomceran (ID);Vometron (ID);Vomiof (IN);Vomiz (TW);Yatrox (ES);Zetron (TH);Zilfujim (AU);Zofer (ZA);Zofran (AE, AR, AT, AU, BB, BE, BF, BG, BH, BJ, BM, BR, BS, BZ, CH, CI, CN, CY, CZ, DE, DK, EC, EE, EG, ES, ET, FI, GB, GH, GM, GN, GY, HK, HR, HU, ID, IE, IL, IQ, IR, IS, IT, JM, JO, JP, KE, KR, KW, LB, LR, LT, LU, LV, LY, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NL, NO, OM, PE, PH, PK, PL, PT, PY, QA, RU, SA, SC, SD, SE, SI, SK, SL, SN, SR, SY, TN, TR, TT, TW, TZ, UA, UG, VE, VN, YE, ZA, ZM, ZW);Zofran Melt (AE, BH, KW, QA, SA);Zofran ODT (BB);Zofran Zydis (KR);Zofron (GR);Zofsetron (BE);Zondaron (RO);Zophren (FR)For country code abbreviations (show table)Abas MN, Tan PC, Azmi N, Omar SZ. Ondansetron compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol. 2014;123(6):1272-1279. [PubMed 24807340]ACOG Committee on Practice Bulletins-Obstetrics. ACOG practice bulletin No. 189: nausea and vomiting of pregnancy. Obstet Gynecol. 2018;131(1):e15-e30. [PubMed 29266076]Afonso N, Dang A, Namshikar V, Kamat S, Rataboli PV. Intravenous ondansetron causing severe bradycardia: two cases. Ann Card Anaesth. 2009;12(2):172-173. doi:10.4103/0971-9784.53433 [PubMed 19602754]Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319. [PubMed 11487763]Al-Ansari K, Alomary S, Abdulateef H, et al, "Metoclopramide Versus Ondansetron for the Treatment of Vomiting in Children With Acute Gastroenteritis," J Pediatr Gastroenterol Nutr, 2011, 53(2):156-60. [PubMed 21788756]Alexandraki I, Smetana GW. Acute viral gastroenteritis in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 30, 2021.Amant F, Berveiller P, Boere IA, et al. Gynecologic cancers in pregnancy: guidelines based on a third international consensus meeting. Ann Oncol. 2019;30(10):1601-1612. doi:10.1093/annonc/mdz228 [PubMed 31435648]Andreoli CM, Gardiner MF. Open globe injuries: Emergency evaluation and initial management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 5, 2020.Anderka M, Mitchell AA, Louik C, et al, "Medications Used to Treat Nausea and Vomiting of Pregnancy and the Risk of Selected Birth Defects," Birth Defects Res A Clin Mol Teratol, 2012, 94(1):22-30. [PubMed 22102545]Apfel CC, Korttila K, Abdalla M, et al; IMPACT Investigators. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med. 2004;350(24):2441-2451. [PubMed 15190136]Applegate GL, Mittal BB, Kletzel M, et al. Outpatient total body irradiation prior to bone marrow transplantation in pediatric patients: a feasibility analysis. Bone Marrow Transplant. 1998;21(7):651-652. [PubMed 9578303]Barrett TW, DiPersio DM, Jenkins CA, et al. A randomized, placebo-controlled trial of ondansetron, metoclopramide, and promethazine in adults. Am J Emerg Med. 2011;29(3):247-255. doi: 10.1016/j.ajem.2009.09.028. [PubMed 20825792]Based on expert opinion.Blumenthal KG, Peter JG, Trubiano JA, Phillips EJ. Antibiotic allergy. Lancet. 2019;393(10167):183-198. doi:10.1016/S0140-6736(18)32218-9 [PubMed 30558872]Bollag L, Lim G, Sultan P, et al. Society for Obstetric Anesthesia and Perinatology: Consensus statement and recommendations for enhanced recovery after cesarean. Anesth Analg. 2021;132(5):1362-1377. doi:10.1213/ANE.0000000000005257 [PubMed 33177330]Bousquet PJ, Co-Minh HB, Demoly P. Isolated urticaria to ondansetron and successful treatment with granisetron. Allergy. 2005;60(4):543-544. doi:10.1111/j.1398-9995.2005.00754.x [PubMed 15727597]Braude D, Crandall C. Ondansetron versus promethazine to treat acute undifferentiated nausea in the emergency department: a randomized, double-blind, noninferiority trial. Acad Emerg Med. 2008;15(3):209-215. doi: 10.1111/j.1553-2712.2008.00060.x. [PubMed 18304050]Bredeson C, Perry G, Martens C, et al. Outpatient total body irradiation as a component of a comprehensive outpatient transplant program. Bone Marrow Transplant. 2002;29(8):667-671. [PubMed 12180111]Bryson JC. Clinical safety of ondansetron. Semin Oncol. 1992;19(6 Suppl 15):26-32. [PubMed 1485179]Bursztejn AC, Tréchot P, Cuny JF, Schmutz JL, Barbaud A. Cutaneous adverse drug reactions during chemotherapy: consider non-antineoplastic drugs. Contact Dermatitis. 2008;58(6):365-368. doi:10.1111/j.1600-0536.2007.01285.x [PubMed 18503688]Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L; American College of Gastroenterology clinical guideline: management of gastroparesis. Am J Gastroenterol. 2013;108(1):18-37. doi: 10.1038/ajg.2012.373. [PubMed 23147521]Camilleri M. Treatment of gastroparesis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 21, 2020.Campbell K, Rowe H, Azzam H, Lane CA. The management of nausea and vomiting of pregnancy. J Obstet Gynaecol Can. 2016;38(12):1127-1137. doi:10.1016/j.jogc.2016.08.009 [PubMed 27986189]Carden PA, Mitchell SL, Waters KD, et al, “Prevention of Cyclophosphamide/Cytarabine-Induced Emesis With Ondansetron in Children With Leukemia,” J Clin Oncol, 1990, 8(9):1531-5. [PubMed 2144019]Celio L, Niger M, Ricchini F, Agustoni F. Palonosetron in the prevention of chemotherapy-induced nausea and vomiting: an evidence-based review of safety, efficacy, and place in therapy. Core Evid. 2015;10:75-87. doi:10.2147/CE.S65555. [PubMed 26345982]Centers for Disease Control and Prevention (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm [PubMed 6810084]Centers for Disease Control and Prevention, "Managing Acute Gastroenteritis Among Children: Oral Rehydration, Maintenance, and Nutritional Therapy," MMWR Recomm Rep, 2003, 52(RR-16):1-16.Chandrakala R, Vijayashankara CN, Kumar KK, Sarala N. Ondansetron induced fatal ventricular tachycardia. Indian J Pharmacol. 2008;40(4):186-187. doi:10.4103/0253-7613.43168 [PubMed 20040955]Charbit B, Albaladejo P, Funck-Brentano C, Legrand M, Samain E, Marty J. Prolongation of QTc interval after postoperative nausea and vomiting treatment by droperidol or ondansetron. Anesthesiology. 2005;102(6):1094-1100. doi:10.1097/00000542-200506000-00006 [PubMed 15915019]Charbit B, Alvarez JC, Dasque E, Abe E, Démolis JL, Funck-Brentano C. Droperidol and ondansetron-induced QT interval prolongation: a clinical drug interaction study. Anesthesiology. 2008;109(2):206-212. doi:10.1097/ALN.0b013e31817fd8c8 [PubMed 18648229]Chen M, Tanner A, Gallo-Torres H. Anaphylactoid-anaphylactic reactions associated with ondansetron. Ann Intern Med. 1993;119(8):862. doi:10.7326/0003-4819-119-8-199310150-00026 [PubMed 8379613]Cherian A, Maguire M. Transient blindness following intravenous ondansetron. Anaesthesia. 2005;60(9):938-939. doi:10.1111/j.1365-2044.2005.04348.x [PubMed 16115266]Chilkoti G, Mohta M, Wadhwa R, Kumar M. The big "little problem" with postoperative nausea and vomiting prophylaxis. Indian J Anaesth. 2015;59(1):60-61. doi:10.4103/0019-5049.149464 [PubMed 25684821]Cohen R, Shlomo M, Dil DN, Dinavitser N, Berkovitch M, Koren G. Intestinal obstruction in pregnancy by ondansetron. Reprod Toxicol. 2014;50:152-153. doi:10.1016/j.reprotox.2014.10.014 [PubMed 25461913]Corapçioglu F, Sarper N. A prospective randomized trial of the antiemetic efficacy and cost-effectiveness of intravenous and orally disintegrating tablet of ondansetron in children with cancer. Pediatr Hematol Oncol. 2005;22(2):103-114. doi:10.1080/08880010590896468 [PubMed 15804995]DeCamp LR, Byerley JS, Doshi N, et al, "Use of Antiemetic Agents in Acute Gastroenteritis: A Systematic Review and Meta-analysis," Arch Pediatr Adolesc Med, 2008, 162(9):858-65. [PubMed 18762604]Demir HA, Batu ED, Yalçın B, Civelek E, Saçkesen C, Büyükpamukçu M. Anaphylactic reaction owing to ondansetron administration in a child with neuroblastoma and safe use of granisetron: a case report. J Pediatr Hematol Oncol. 2010;32(8):e341-e342. doi:10.1097/MPH.0b013e3181ea214a [PubMed 20921907]Diaz-Parlet J, Subramani S. Dystonic reaction associated with ondansetron administration in a patient with normal pressure hydrocephalus. J Clin Anesth. 2015;27(5):423-425. doi:10.1016/j.jclinane.2015.03.037 [PubMed 25935832]Dormuth CR, Winquist B, Fisher A, et al; Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Comparison of pregnancy outcomes of patients treated with ondansetron vs alternative antiemetic medications in a multinational, population-based cohort. JAMA Netw Open. 2021;4(4):e215329. doi:10.1001/jamanetworkopen.2021.5329 [PubMed 33890993]Dupuis LL, Boodhan S, Holdsworth M, et al; Pediatric Oncology Group of Ontario. Guideline for the prevention of acute nausea and vomiting due to antineoplastic medication in pediatric cancer patients. Pediatr Blood Cancer. 2013;60(7):1073-1082. [PubMed 23512831]Egerton-Warburton D, Meek R, Mee MJ, Braitberg G. Antiemetic use for nausea and vomiting in adult emergency department patients: randomized controlled trial comparing ondansetron, metoclopramide, and placebo. Ann Emerg Med. 2014;64(5):526-532.e1. doi: 10.1016/j.annemergmed.2014.03.017. [PubMed 24818542]Einarson A, Maltepe C, Navioz Y, et al, "The Safety of Ondansetron for Nausea and Vomiting of Pregnancy: A Prospective Comparative Study," BJOG, 2004, 111(9):940-3. [PubMed 15327608]Elkomy MH, Sultan P, Carvalho B, et al. Ondansetron pharmaco*kinetics in pregnant women and neonates: towards a new treatment for neonatal abstinence syndrome. Clin Pharmacol Ther. 2015;97(2):167-176. doi:10.1002/cpt.5 [PubMed 25670522]Farah RA, Aquino VM, Munoz LL, Sandler ES. Safety and cost-effectiveness of outpatient total body irradiation in pediatric patients undergoing stem cell transplantation. J Pediatr Hematol Oncol. 1998;20(4):319-321. [PubMed 9703004]FDA. FDA drug safety communication: new information regarding QT prolongation with ondansetron (Zofran). https://www.fda.gov/Drugs/DrugSafety/ucm310190.htm. Published June 29, 2012. Accessed July 10, 2013.Feinleib J, Kwan L, Yamani A. Postoperative nausea and vomiting. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 5, 2021.Fernando SL, Broadfoot AJ. Ondansetron anaphylaxis: a case report and protocol for skin testing. Br J Anaesth. 2009;102(2):285-286. doi:10.1093/bja/aen376 [PubMed 19151059]Ferreira E, Gillet M, Lelièvre J, et al, "Ondansetron Use During Pregnancy: A Case Series," J Popul Ther Clin Pharmacol, 2012, 19(1):e1-e10. [PubMed 22267256]Feyer P, Jordan K. Radiotherapy-induced nausea and vomiting: Prophylaxis and treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 5, 2020.Fleisher DR. Management of cyclic vomiting syndrome. J Pediatr Gastroenterol Nutr. 1995;21 Suppl 1:S52-S56. doi:10.1097/00005176-199501001-00015 [PubMed 8708870]Freedman SB, Adler M, Seshadri R, et al, "Oral Ondansetron for Gastroenteritis in a Pediatric Emergency Department," N Engl J Med, 2006, 354(16):1698-705. [PubMed 16625009]Freedman SB, Uleryk E, Rumantir M, Finkelstein Y. Ondansetron and the risk of cardiac arrhythmias: a systematic review and postmarketing analysis. Ann Emerg Med. 2014;64(1):19-25.e6. doi:10.1016/j.annemergmed.2013.10.026 [PubMed 24314899]Furman JM, Barton JJS. Treatment of vertigo. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 28, 2022.Furyk JS, Meek RA, Egerton-Warburton D. Drugs for the treatment of nausea and vomiting in adults in the emergency department setting. Cochrane Database Syst Rev. 2015;(9):CD010106. doi: 10.1002/14651858.CD010106.pub2. [PubMed 26411330]Gallagher SA, Hackett P. Acute mountain sickness and high altitude cerebral edema. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 18, 2018.Gan TJ, Diemunsch P, Habib AS, et al; Society for Ambulatory Anesthesia. Consensus guidelines for the management of postoperative nausea and vomiting [published corrections appear in Anesth Analg. 2015;120(2):494; Anesth Analg. 2014;118(3):689]. Anesth Analg. 2014;118(1):85-113. doi:10.1213/ANE.0000000000000002. [PubMed 24356162]Ganjare A, Kulkarni AP. Comparative electrocardiographic effects of intravenous ondansetron and granisetron in patients undergoing surgery for carcinoma breast: a prospective single-blind randomised trial. Indian J Anaesth. 2013;57(1):41-45. doi:10.4103/0019-5049.108560 [PubMed 23716765]García Núñez I, Algaba Mármol MA, Reina Ariza E. Ondansetron hypersensitivity: a clinical diagnosis protocol and cross-reactivity study. J Investig Allergol Clin Immunol. 2015;25(3):221-222. [PubMed 26182691]Garsed K, Chernova J, Hastings M, et al. A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea. Gut. 2014;63(10):1617-1625. doi:10.1136/gutjnl-2013-305989 [PubMed 24334242]George M, Al-Duaij N, O'Donnell KA, Shannon MW. Obtundation and seizure following ondansetron overdose in an infant. Clin Toxicol (Phila). 2008;46(10):1064-1066. doi:10.1080/15563650802304401 [PubMed 18803119]Gore S, Gilmore IT, Haigh CG, Brownless SM, Stockdale H, Morris AI. Colonic transit in man is slowed by ondansetron (GR38032F), a selective 5-hydroxytryptamine receptor (type 3) antagonist. Aliment Pharmacol Ther. 1990;4(2):139-144. doi:10.1111/j.1365-2036.1990.tb00458.x [PubMed 2151757]Goyal P, Paramesh K, Puranik S, Proctor M, Sanghvi M. Delayed diagnosis of anaphylaxis secondary to ondansetron: a case report. Eur J Anaesthesiol. 2016;33(2):146-147. doi:10.1097/EJA.0000000000000372 [PubMed 26555872]Griffiths JD, Gyte GM, Paranjothy S, Brown HC, Broughton HK, Thomas J. Interventions for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section. Cochrane Database Syst Rev. 2012;9(9):CD007579. doi: 10.1002/14651858.CD007579.pub2 [PubMed 22972112]Grover VK, Mathew PJ, Hegde H. Efficacy of orally disintegrating ondansetron in preventing postoperative nausea and vomiting after laparoscopic cholecystectomy: a randomised, double-blind placebo controlled study. Anaesthesia. 2009;64(6):595-600. doi: 10.1111/j.1365-2044.2008.05860.x. [PubMed 19453311]Habib AS, George RB, McKeen DM, et al. Antiemetics added to phenylephrine infusion during cesarean delivery: a randomized controlled trial. Obstet Gynecol. 2013;121(3):615-623. doi:10.1097/AOG.0b013e3182839fee [PubMed 23635626]Hafermann MJ, Namdar R, Seibold GE, Page RL 2nd. Effect of intravenous ondansetron on QT interval prolongation in patients with cardiovascular disease and additional risk factors for torsades: a prospective, observational study. Drug Healthc Patient Saf. 2011;3:53-58. doi:10.2147/DHPS.S25623 [PubMed 22046106]Havrilla PL, Kane-Gill SL, Verrico MM, Seybert AL, Reis SE. Coronary vasospasm and atrial fibrillation associated with ondansetron therapy. Ann Pharmacother. 2009;43(3):532-536. doi:10.1345/aph.1L544 [PubMed 19261954]Health Canada. Zofran (ondansetron) - dosage and administration of intravenous ondansetron in geriatrics (>65 years of age) - for health professionals - recalls and safety alerts. http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/39943a-eng.php. Published June 12, 2014. Accessed September 18, 2018.Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: ASCO guideline update. J Clin Oncol. 2020;38(24):2782-2797. doi:10.1200/JCO.20.01296 [PubMed 32658626]Hesketh PJ. Prevention and treatment of chemotherapy-induced nausea and vomiting in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 15, 2021.Hewitt M, McQuade B, Stevens R. The efficacy and safety of ondansetron in the prophylaxis of cancer-chemotherapy induced nausea and vomiting in children. Clin Oncol (R Coll Radiol). 1993;5(1):11-14. doi:10.1016/s0936-6555(05)80686-7 [PubMed 8424909]Holdsworth MT, Raisch DW, and Frost J, "Acute and Delayed Nausea and Emesis Control in Pediatric Oncology Patients," Cancer, 2006, 106(4):931-40. [PubMed 16404740]Iammatteo M, Keskin T, Jerschow E. Evaluation of periprocedural hypersensitivity reactions. Ann Allergy Asthma Immunol. 2017;119(4):349-355.e2. doi:10.1016/j.anai.2017.07.013 [PubMed 28866307]"Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics (AAP) Committee on Drugs. Pediatrics. 1997;99(2):268-278. [PubMed 9024461]Jelting Y, Klein C, Harlander T, Eberhart L, Roewer N, Kranke P. Preventing nausea and vomiting in women undergoing regional anesthesia for cesarean section: challenges and solutions. Local Reg Anesth. 2017;10:83-90. [PubMed 28860857]Kaplan YC, Richardson JL, Keskin-Arslan E, Erol-Coskun H, Kennedy D. Use of ondansetron during pregnancy and the risk of major congenital malformations: a systematic review and meta-analysis. Reprod Toxicol. 2019;86:1-13. doi:10.1016/j.reprotox.2019.03.001 [PubMed 30849498]Kataja V, de Bruijn KM. Hypersensitivity reactions associated with 5- hydroxytryptamine(3)-receptor antagonists: a class effect?. Lancet. 1996;347(9001):584-585. doi:10.1016/s0140-6736(96)91275-1 [PubMed 8596322]Kenny GN, Oates JD, Leeser J, et al. Efficacy of orally administered ondansetron in the prevention of postoperative nausea and vomiting: a dose ranging study. Br J Anaesth. 1992;68(5):466-470. [PubMed 1386523]Khan RB. Migraine-type headaches in children receiving chemotherapy and ondansetron. J Child Neurol. 2002;17(11):857-858. doi:10.1177/08830738020170111706 [PubMed 12585731]Kiesewetter B and Raderer M. Ondansetron for diarrhea associated with neuroendocrine tumors. N Engl J Med. 2013;368(20):1947-1948. doi:10.1056/NEJMc1301537. [PubMed 23675671]Koren G, "Motherisk Update. Is Ondansetron Safe for Use During Pregnancy?" Can Fam Physician, 2012, 58(10):1092-3. [PubMed 23064917]Kossey JL, Kwok KK. Anaphylactoid reactions associated with ondansetron. Ann Pharmacother. 1994;28(9):1029-1030. doi:10.1177/106002809402800906 [PubMed 7803876]Kovács G, Wachtel AE, Basharova EV, Spinelli T, Nicolas P, Kabickova E. Palonosetron versus ondansetron for prevention of chemotherapy-induced nausea and vomiting in paediatric patients with cancer receiving moderately or highly emetogenic chemotherapy: a randomised, phase 3, double-blind, double-dummy, non-inferiority study. Lancet Oncol. 2016;17(3):332-344. doi:10.1016/S1470-2045(15)00520-3 [PubMed 26795844]Lavecchia M, Chari R, Campbell S, Ross S. Ondansetron in pregnancy and the risk of congenital malformations: a systematic review. J Obstet Gynaecol Can. 2018;40(7):910-918. doi:10.1016/j.jogc.2017.10.024 [PubMed 29754832]Lebrun C, Chichmanian RM, Peyrade F, Chatel M, Frenay M. Recurrent bowel occlusion with oral ondansetron with no side effects of the intravenous route: a previously unknown adverse event. Ann Oncol. 1997;8(9):919-920. doi:10.1023/a:1008205308867 [PubMed 9358948]Lee DY, Trinh T, Roy SK. Torsades de pointes after ondansetron infusion in 2 patients. Tex Heart Inst J. 2017;44(5):366-369. doi:10.14503/THIJ-16-6040 [PubMed 29259513]Lemon LS, Bodnar LM, Garrard W, et al. Ondansetron use in the first trimester of pregnancy and the risk of neonatal ventricular septal defect. Int J Epidemiol. 2020;49(2):648-656. doi:10.1093/ije/dyz255 [PubMed 31860078]Lemon LS, Zhang H, Hebert MF, et al. Ondansetron exposure changes in a pregnant woman. Pharmacotherapy. 2016;36(9):e139-e141. doi: 10.1002/phar.1796. [PubMed 27374186]Leung J, Guyer A, Banerji A. IgE-mediated hypersensitivity to ondansetron and safe use of palonosetron. J Allergy Clin Immunol Pract. 2013;1(5):526-527. doi:10.1016/j.jaip.2013.05.004 [PubMed 24565629]Li BU, Lefevre F, Chelimsky GG, et al, "North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Consensus Statement on the Diagnosis and Management of Cyclic Vomiting Syndrome," J Pediatr Gastroenterol Nutr, 2008, 47(3):379-93. [PubMed 18728540]Li K, Vo K, Lee BK, Addo N, Coralic Z. Effect of a single dose of i.v. ondansetron on QTc interval in emergency department patients. Am J Health Syst Pharm. 2018;75(5):276-282. doi:10.2146/ajhp161070 [PubMed 29317399]Macachor JD, Kurniawan M, Loganathan SB. Ondansetron-induced oculogyric crisis. Eur J Anaesthesiol. 2014;31(12):712-713. doi:10.1097/EJA.0000000000000169 [PubMed 25303969]Macones GA, Caughey AB, Wood SL, et al. Guidelines for postoperative care in cesarean delivery: Enhanced Recovery After Surgery (ERAS) Society recommendations (part 3). Am J Obstet Gynecol. 2019;221(3):247.e1-247.e9. doi:10.1016/j.ajog.2019.04.012 [PubMed 30995461]Maitra A, Bhattacharyya S, Paik S, Pathak P, Tripathi SK. A rare case of fixed drug eruption due to ondansetron. Iran J Med Sci. 2017;42(5):497-500. [PubMed 29234184]Marty M, Pouillart P, Scholl S, et al, “Comparison of the 5-hydroxytryptamine 3 (Serotonin) Antagonist Ondansetron (GR 38032F) With High-Dose Metoclopramide in the Control of Cisplatin-Induced Emesis,” N Engl J Med, 1990, 322(12):816-21. [PubMed 2137902]Moffett PM, Cartwright L, Grossart EA, O'Keefe D, Kang CS. Intravenous ondansetron and the QT interval in adult emergency department patients: an observational study. Acad Emerg Med. 2016;23(1):102-105. doi:10.1111/acem.12836 [PubMed 26720490]Mondick JT, Johnson BM, Haberer LJ, et al, "Population Pharmaco*kinetics of Intravenous Ondansetron in Oncology and Surgical Patients Aged 1-48 Months," Eur J Clin Pharmacolm, 2010, 66(1):77-86. [PubMed 19798490]Moskowitz HS, Dinces EA. Meniere disease: Evaluation, diagnosis, and management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 2, 2022.Murray KL, Wright D, Laxton B, Miller KM, Meyers J, Englebright J. Implementation of standardized pediatric i.v. medication concentrations. Am J Health Syst Pharm. 2014;71(17):1500-1508. [PubMed 25147175]National Institute for Health and Care Excellence. Drug allergy: diagnosis and management. Published September 3, 2014. Accessed October 23, 2020. https://www.nice.org.uk/guidance/cg183Navari RM, Koeller JM. Electrocardiographic and cardiovascular effects of the 5-hydroxytryptamine3 receptor antagonists. Ann Pharmacother. 2003;37(9):1276-1286. doi:10.1345/aph.1C510 [PubMed 12921512]Navari RM, Qin R, Ruddy KJ, et al. Olanzapine for the prevention of chemotherapy-induced nausea and vomiting. N Engl J Med. 2016;375(2):134-142. doi: 10.1056/NEJMoa1515725. [PubMed 27410922]Niebyl JR. Clinical practice. Nausea and vomiting in pregnancy [published correction appears in N Engl J Med. 2010;363(21):2078]. N Engl J Med. 2010;363(16):1544-1550. doi: 10.1056/NEJMcp1003896. [PubMed 20942670]O'Donohue JW, Pereira SP, Ashdown AC, Haigh CG, Wilkinson JR, Williams R. A controlled trial of ondansetron in the pruritus of cholestasis. Aliment Pharmacol Ther. 2005;21(8):1041-1045. doi:10.1111/j.1365-2036.2005.02430.x [PubMed 15813840]Oliveira LG, Capp SM, You WB, Riffenburgh RH, Carstairs SD. Ondansetron compared with doxylamine and pyridoxine for treatment of nausea in pregnancy: a randomized controlled trial. Obstet Gynecol. 2014;124(4):735-742. [PubMed 25198265]Olver I, Paska W, Depierre A, et al. A multicentre, double-blind study comparing placebo, ondansetron and ondansetron plus dexamethasone for the control of cisplatin-induced delayed emesis. Ondansetron Delayed Emesis Study Group. Ann Oncol. 1996;7(9):945-952. doi:10.1093/oxfordjournals.annonc.a010798 [PubMed 9006746]Ondansetron Hydrochloride oral solution, USP (ondansetron hydrochloride) oral [prescribing information]. Eatontown, NJ: West Ward Pharmaceuticals Corp; September 2018.Ondansetron hydrochloride tablet [prescribing information]. Cranbury, NJ: Sun Pharmaceutical Industries, Inc; November 2018.Ondansetron injection (ondansetron hydrochloride) IV or IM [prescribing information]. E. Windsor, NJ: AuroMedics Pharma LLC; October 2021.Ondansetron injection [summary of product characteristics]. Gloucester, UK: Nexus; May 2020.Pan PH, Lee SC, Harris LC. Antiemetic prophylaxis for postdischarge nausea and vomiting and impact on functional quality of living during recovery in patients with high emetic risks: a prospective, randomized, double-blind comparison of two prophylactic antiemetic regimens. Anesth Analg. 2008;107(2):429-38. doi: 10.1213/ane.0b013e318172f992. [PubMed 18633020]Pasternak B, Svanström H, and Hviid A, "Ondansetron in Pregnancy and Risk of Adverse Fetal Outcomes," N Engl J Med, 2013, 368(9):814-23. [PubMed 23445092]Patanwala AE, Amini R, Hays DP, Rosen P. Antiemetic therapy for nausea and vomiting in the emergency department. J Emerg Med. 2010;39(3):330-336. doi:10.1016/j.jemermed.2009.08.060. [PubMed 20022195]Patel E, Rosemond D, Afzal A. Ondansetron induced torsades de pointes. Clin Case Rep. 2019;7(8):1557-1558. doi:10.1002/ccr3.2251 [PubMed 31428390]Patel P, Robinson PD, Thackray J, et al. Guideline for the prevention of acute chemotherapy-induced nausea and vomiting in pediatric cancer patients: a focused update. Pediatr Blood Cancer. 2017:e26542. doi: 10.1002/pbc.26542. [PubMed 28453189]Patka J, Wu DT, Abraham P, Sobel RM. Randomized controlled trial of ondansetron vs. prochlorperazine in adults in the emergency department. West J Emerg Med. 2011;12(1):1-5. [PubMed 21691464]Phillips RS, Gopaul S, Gibson F, et al, "Antiemetic Medication for Prevention and Treatment of Chemotherapy Induced Nausea and Vomiting in Childhood," Cochrane Database Syst Rev, 2010, (9):CD007786. [PubMed 20824866]Piche T, Vanbiervliet G, Cherikh F, et al. Effect of ondansetron, a 5-HT3 receptor antagonist, on fatigue in chronic hepatitis C: a randomised, double blind, placebo controlled study. Gut. 2005;54(8):1169-1173. doi:10.1136/gut.2004.055251 [PubMed 16009690]Picot C, Berard A, Grenet G, Ripoche E, Cucherat M, Cottin J. Risk of malformation after ondansetron in pregnancy: An updated systematic review and meta-analysis. Birth Defects Res. Published online 2020. doi:10.1002/bdr2.1705 [PubMed 32420702]Pinkerton CR, Williams D, Wootton C, et al, “5-HT3 Antagonist Ondansetron - An Effective Outpatient Antiemetic in Cancer Treatment,” Arch Dis Child, 1990, 65(8):822-5. [PubMed 2144721]Platt AJ, Heddle RM, Rake MO, et al. Ondansetron in carcinoid syndrome. Lancet. 1992;339(8806):1416. [PubMed 1375972]Popovic M, Warr DG, Deangelis C, et al. Efficacy and safety of palonosetron for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis of randomized controlled trials. Support Care Cancer. 2014;22(6):1685-1697. doi: 10.1007/s00520-014-2175-6. [PubMed 24590374]Priestman TJ, Roberts JT, Lucraft H, et al. Results of a randomized, double-blind comparative study of ondansetron and metoclopramide in the prevention of nausea and vomiting following high-dose upper abdominal irradiation. Clin Oncol (R Coll Radiol). 1990;2(2):71-75. [PubMed 1702012]Priestman TJ, Roberts JT, Upadhyaya BK. A prospective randomized double-blind trial comparing ondansetron versus prochlorperazine for the prevention of nausea and vomiting in patients undergoing fractionated radiotherapy. Clin Oncol (R Coll Radiol). 1993;5(6):358-363. [PubMed 8305355]Rapp JH, Yuen M, Abraham T. Bradycardia after intravenous ondansetron with asystole on rechallenge: a case report. Hosp Pharm. 2015;50(10):918-921. doi:10.1310/hpj5010-918 [PubMed 27729680]Refer to manufacturer's labeling.Rice GP, Ebers GC. Ondansetron for intractable vertigo complicating acute brainstem disorders. Lancet. 1995;345(8958):1182-1183. [PubMed 7723573]Ritter MJ, Goodman BP, Sprung J, Wijdicks EF. Ondansetron-induced multifocal encephalopathy. Mayo Clin Proc. 2003;78(9):1150-1152. doi:10.4065/78.9.1150 [PubMed 12962170]Roila F, Del Favero A. Ondansetron clinical pharmaco*kinetics. Clin Pharmaco*kinet. 1995;29(2):95-109. doi:10.2165/00003088-199529020-00004 [PubMed 7586904]Roila F, Molassiotis A, Herrstedt J, et al. 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Ann Oncol. 2016;27(suppl 5):v119-v133. [PubMed 27664248]Ruff P, Paska W, Goedhals L, et al. Ondansetron compared with granisetron in the prophylaxis of cisplatin-induced acute emesis: a multicentre double-blind, randomised, parallel-group study. The Ondansetron and Granisetron Emesis Study Group [published correction appears in Oncology. 1994;51(3):243]. Oncology. 1994;51(1):113-118. doi:10.1159/000227321 [PubMed 8265095]Ruktrirong J, Traivaree C, Monsereenusorn C, Photia A, Lertvivatpong N, Rujkijyanont P. Single daily dosing versus divided dosing intravenous ondansetron to prevent chemotherapy-induced nausea and vomiting among children: A comparative randomized double-blind controlled trial. Pediatr Blood Cancer. Published online March 23, 2021. doi:10.1002/pbc.29002 [PubMed 33754455]Saberi A, Pourshafie SH, Kazemnejad-Leili E, Nemati S, Sutohian S, Sayad-Fathi S. Ondansetron or promethazine: which one is better for the treatment of acute peripheral vertigo? Am J Otolaryngol. 2019;40(1):10-15. doi:10.1016/j.amjoto.2018.09.010 [PubMed 30268346]Salvucci AA, Squire B, Burdick M, Luoto M, Brazzel D, Vaezazizi R. Ondansetron is safe and effective for prehospital treatment of nausea and vomiting by paramedics. Prehosp Emerg Care. 2011;15(1):34-38. doi: 10.3109/10903127.2010.519822. [PubMed 21091329]Samanta S, Jain K, Samanta S, Ghatak T. Intraoperative pulseless ventricular tachycardia after Ondansetron. J Anaesthesiol Clin Pharmacol. 2014;30(2):293-294. doi:10.4103/0970-9185.130123 [PubMed 24803784]Sandoval C, Corbi D, Strobino B, Fevzi Ozkaynak M, Tugal O, Jayabose S. Randomized double-blind comparison of single high-dose ondansetron and multiple standard-dose ondansetron in chemotherapy-naive pediatric oncology patients. Cancer Invest. 1999;17(5):309-313. doi:10.3109/07357909909032871 [PubMed 10370357]Saraogi PP, Nayak CS, Pereira RR, Dhurat RS. Inadvertent provocative oral ondansetron use leading to toxic epidermal necrolysis in an HIV-infected patient. Indian J Dermatol. 2012;57(6):503. doi:10.4103/0019-5154.103082 [PubMed 23248379]Schwörer H, Münke H, Stöckmann F, Ramadori G. Treatment of diarrhea in carcinoid syndrome with ondansetron, tropisetron, and clonidine. Am J Gastroenterol. 1995;90(4):645-648. [PubMed 7717328]Seynaeve C, Schuller J, Buser K, et al, “Comparison of the Anti-emetic Efficacy of Different Doses of Ondansetron, Given as Either a Continuous Infusion or a Single Intravenous Dose, in Acute Cisplatin-Induced Emesis,” Br J Cancer 1992, 66(1):192-7. [PubMed 1386245]Sharma R, Panda A. Ondansetron-induced headache in a parturient mimicking postdural puncture headache. Can J Anaesth. 2010;57(2):187-188. doi:10.1007/s12630-009-9226-3 [PubMed 20043218]Singh V, Sinha A, Prakash N. Ondansetron-induced migraine-type headache. Can J Anaesth. 2010;57(9):872-873. doi:10.1007/s12630-010-9350-0 [PubMed 20661681]Siu SS, Chan MT, and Lau TK, "Placental Transfer of Ondansetron During Early Human Pregnancy," Clin Pharmaco*kinet, 2006, 45(4):419-23. [PubMed 16584287]Smith JA, Fox KA. Treatment and outcome of nausea and vomiting of pregnancy. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 11, 2021.Spahr-Schopfer IA, Lerman J, Sikich N, et al, “Pharmaco*kinetics of Intravenous Ondansetron in Healthy Children Undergoing Ear, Nose, and Throat Surgery,” Clin Pharmacol Ther, 1995, 58(3):316-21. [PubMed 7554705]Spector JI, Lester EP, Chevlen EM, et al, “A Comparison of Oral Ondansetron and Intravenous Granisetron for the Prevention of Nausea and Emesis Associated With Cisplatin-Based Chemotherapy,” Oncologist, 1998, 3(6):432-438. [PubMed 10388135]Spiller R. Serotonergic modulating drugs for functional gastrointestinal diseases. Br J Clin Pharmacol. 2002;54(1):11-20. doi:10.1046/j.1365-2125.2002.01612.x [PubMed 12100220]Spitzer TR, Friedman CJ, Bushnell W, Frankel SR, Raschko J. Double-blind, randomized, parallel-group study on the efficacy and safety of oral granisetron and oral ondansetron in the prophylaxis of nausea and vomiting in patients receiving hyperfractionated total body irradiation. Bone Marrow Transplant. 2000;26(2):203-210. [PubMed 10918432]Sprung J, Choudhry FM, Hall BA. Extrapyramidal reactions to ondansetron: cross-reactivity between ondansetron and prochlorperazine?. Anesth Analg. 2003;96(5):1374-1376. doi:10.1213/01.ane.0000058845.72102.f2 [PubMed 12707136]Svanberg A, Birgegård G. Addition of aprepitant (Emend) to standard antiemetic regimen continued for 7 days after chemotherapy for stem cell transplantation provides significant reduction of vomiting. Oncology. 2015;89(1):31-36. doi: 10.1159/000371523. [PubMed 25659986]Talley NJ, Phillips SF, Haddad A, et al. GR 38032F (ondansetron), a selective 5HT3 receptor antagonist, slows colonic transit in healthy man. Dig Dis Sci. 1990;35(4):477-480. doi:10.1007/BF01536922 [PubMed 2138532]Tan J, Mehr S. Anaphylaxis to an ondansetron wafer. J Paediatr Child Health. 2012;48(6):543-544. doi:10.1111/j.1440-1754.2011.02124.x [PubMed 21679335]Tan PC and Omar SZ, "Contemporary Approaches to Hyperemesis During Pregnancy," Curr Opin Obstet Gynecol, 2011, 23(2):87-93. [PubMed 21297474]Theal JJ, Toosi MN, Girlan L, et al. A randomized, controlled crossover trial of ondansetron in patients with primary biliary cirrhosis and fatigue. Hepatology. 2005;41(6):1305-1312. doi:10.1002/hep.20698 [PubMed 15915460]Trivedi S, Schiltz B, Kanipakam R, Bos JM, Ackerman MJ, Ouellette Y. Effect of ondansetron on QT interval in patients cared for in the PICU. Pediatr Crit Care Med. 2016;17(7):e317-e323. doi:10.1097/PCC.0000000000000776 [PubMed 27387786]Veneziano M, Framarino Dei Malatesta M, Bandiera AF, Fiorelli C, Galati M, Paolucci A. Ondansetron-induced headache. Our experience in gynecological cancer. Eur J Gynaecol Oncol. 1995;16(3):203-207. [PubMed 7664768]Weiss KS. Anaphylactic reaction to ondansetron. Arch Intern Med. 2001;161(18):2263. doi:10.1001/archinte.161.18.2263 [PubMed 11575988]White L, Daly SA, McKenna CJ, et al. A comparison of oral ondansetron syrup or intravenous ondansetron loading dose regimens given in combination with dexamethasone for the prevention of nausea and emesis in pediatric and adolescent patients receiving moderately/highly emetogenic chemotherapy. Pediatr Hematol Oncol. 2000;17(6):445-455. doi:10.1080/08880010050120791 [PubMed 10989464]WHO Pharmaceuticals Newsletter. Ondansetron and serotonin syndrome. 2012; 3:16-21.Wymenga AN, de Vries EG, Leijsma MK, Kema IP, Kleibeuker JH. Effects of ondansetron on gastrointestinal symptoms in carcinoid syndrome. Eur J Cancer. 1998;34(8):1293-1294. [PubMed 9849494]Zhou C, Zhu Y, Bao Z, Wang X, Liu Q. Efficacy of ondansetron for spinal anesthesia during cesarean section: a meta-analysis of randomized trials. J Int Med Res. 2018;46(2):654-662. doi:10.1177/0300060517716502 [PubMed 28856920]Zofran injection (ondansetron) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals; April 2021.Zofran tablets and oral solution and Zofran ODT orally disintegrating tablets (ondansetron) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals; October 2021.Zuplenz (ondansetron) [prescribing information]. Warren, NJ: Aquestive Therapeutics; August 2021.Topic 9719 Version 635.0

CloseFluconazole: Pediatric drug informationFluconazole: Pediatric drug information(For additional information see "Fluconazole: Drug information" and see "Fluconazole: Patient drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USDiflucanBrand Names: CanadaACT Fluconazole;APO-Fluconazole;Diflucan;Fluconazole SDZ;MYLAN-Fluconazole;PMS-Fluconazole;PRO-Fluconazole;TARO-Fluconazole;TEVA-FluconazoleTherapeutic CategoryAntifungal Agent, SystemicDosing: NeonatalGeneral dosing, susceptible infection (Ref):Prophylaxis: IV, Oral: 3 to 6 mg/kg/dose twice weekly.Treatment: IV, Oral: Initial: 25 mg/kg on day 1, followed by 12 mg/kg/dose once daily.Candidiasis, prophylaxis for NICUs with high rates (>10%) of invasive candidiasis: Birth weight <1 kg: IV, Oral: 3 to 6 mg/kg/dose twice weekly for up to 6 weeks or until IV access is no longer required; initiate within 48 to 72 hours of birth (Ref); NICU-specific Candida sp. susceptibility patterns/minimum inhibitory concentration (MIC) distributions may be considered when selecting the dose; pharmaco*kinetic simulations suggest that the lower dose (3 mg/kg) provides adequate coverage when MICs ≤2 mcg/mL and a higher dose (6 mg/kg) is necessary when MIC >2 mcg/mL (Ref); when MICs are low within a NICU, 3 mg/kg is likely as efficacious as 6 mg/kg (Ref). Note: Prophylaxis may also be used in NICUs with lower rates of infection for patients who have risk factors (eg, central venous catheters, third-generation cephalosporins, carbapenems) for invasive candidiasis (Ref).Candidiasis, systemic (including Candidemia and invasive candidiasis), treatment: Note: Alternative treatment for patients who have not received fluconazole prophylaxis.IV, Oral: 12 mg/kg/dose once daily (Ref). Based on pharmaco*kinetic studies, a loading dose of 25 mg/kg, followed by 12 mg/kg/dose once daily achieves the desired AUC within 24 hours (Ref). Some experts have suggested 12 mg/kg/dose every 24 to 48 hours for extremely preterm infants PNA <8 days (Ref).Candidiasis, CNS infection, step-down therapy: IV, Oral: 12 mg/kg/dose once daily until all signs, symptoms, and CSF and radiological abnormalities have resolved (Ref).Candidiasis, esophageal; treatment (Ref): Note: Minimum duration of therapy is 3 weeks and for at least 2 weeks following resolution of symptoms:GA 26 to 29 weeks: IV, Oral:PNA ≤14 days: 6 mg/kg/dose every 72 hours; change to every 24 hours once beyond the first 2 weeks of life. Dose up to 12 mg/kg/dose may be used based on clinical response.PNA >14 days: 6 mg/kg/dose once daily; doses up to 12 mg/kg/dose may be used based on clinical response.GA >29 weeks: IV, Oral: 6 mg/kg/dose once daily; doses up to 12 mg/kg/dose may be used based on clinical response.Candidiasis, oropharyngeal (thrush); treatment (Ref):GA 26 to 29 weeks: IV, Oral:PNA ≤14 days: Initial: 6 mg/kg on day 1, followed by 3 to 6 mg/kg/dose every 72 hours; change to every 24 hours once beyond the first 2 weeks of life.PNA >14 days: Initial: 6 mg/kg on day 1, followed by 3 to 6 mg/kg/dose once daily for at least 2 weeks.GA >29 weeks: IV, Oral: Initial: 6 mg/kg on day 1, followed by 3 to 6 mg/kg/dose once daily for at least 2 weeks.Candidiasis, extracorporeal membrane oxygenation (ECMO) patients: Limited data available; dosing based on a pharmaco*kinetic study of pediatric patients (including neonates):Term neonates:Prophylaxis: IV: 12 mg/kg on day 1, followed by 6 mg/kg/dose once daily (Ref).Treatment: IV: 35 mg/kg on day 1, followed by 12 mg/kg/dose once daily (Ref).Coccidioidomycosis, empiric therapy: IV, Oral: 6 to 12 mg/kg/dose once daily until diagnosis is ruled out (Ref).Cryptococcal, CNS disease (meningitis):Acute treatment: Limited data in neonates, other agents preferred: Neonates ≥30 weeks: IV, Oral: 12 mg/kg/dose on day 1, followed by 6 to 12 mg/kg/day for 10 to 12 weeks after CSF culture becomes negative.Consolidation therapy (after treatment with amphotericin B and flucytosine): IV, Oral: 12 mg/kg/dose on day 1, then 10 to 12 mg/kg/dose daily for a minimum of 8 weeks (Ref).Prevention of relapse (HIV-infected patients): IV, Oral: 6 mg/kg/dose once daily (Ref).Dosing adjustment in renal impairment: There are no specific neonatal dosage adjustments provided in the manufacturer's labeling; some experts have suggested the following indication-specific dosing based on pharmaco*kinetic studies (Ref):Candidiasis, prophylaxis: IV, Oral: PNA ≥3 days: Scr ≥1.3 mg/dL: 6 mg/kg/dose once weekly; resume 6 mg/kg/dose twice weekly when Scr is ≤1 mg/dL.Dosing: PediatricGeneral dosing, susceptible infection: Infants, Children, and Adolescents: IV, Oral: Initial: 6 to 12 mg/kg/dose on day 1, followed by 3 to 12 mg/kg/dose once daily; duration and dosage depends on severity of infection; the manufacturer suggests limiting dose to 600 mg/dose; however, higher maximum doses have been used; see specific indications.Candida infections, prophylaxisCandida infections, prophylaxis:Oncology patients at high risk of invasive candidiasis (eg, AML, recurrent ALL, myelodysplastic syndrome [MDS], HSCT recipients): Limited data available: Infants, Children, and Adolescents: IV, Oral: 6 to 12 mg/kg/dose once daily; maximum dose: 400 mg/dose; duration dependent upon type of transplant and/or chemotherapy, consult institution-specific protocols (Ref).Surgical prophylaxis, high-risk patients undergoing liver, pancreas, kidney, or pancreas-kidney transplantation: Infants, Children, and Adolescents: IV: 6 mg/kg as a single dose 60 minutes before procedure; maximum dose: 400 mg/dose; time of initiation and duration varies with transplant type, consult institution-specific protocols (Ref).Candidiasis, systemic, treatmentCandidiasis, systemic (including Candidemia and invasive candidiasis), treatment: Infants, Children, and Adolescents: IV, Oral: 12 mg/kg/dose once daily; maximum dose: 800 mg/dose; continue treatment for ≥14 days after documented clearance, resolution of symptoms, and resolution of neutropenia if present (Ref). An initial loading dose of 25 mg/kg has also been suggested (Ref).Candidiasis, CNS candidiasis, step-down therapyCandidiasis, CNS candidiasis, step-down therapy: Infants, Children, and Adolescents: Oral, IV: 12 mg/kg/dose once daily following initial therapy with liposomal amphotericin B (with or without flucytosine); maximum dose: 800 mg/dose; treatment should continue until all signs, symptoms, and CSF and radiological abnormalities have resolved (Ref).Candidiasis, endophthalmitis, treatmentCandidiasis, endophthalmitis, treatment: Infants, Children, and Adolescents: Oral, IV: 12 mg/kg/dose once daily for at least 4 to 6 weeks until examination indicates resolution; maximum dose: 800 mg/dose. Note: Use in combination with intravitreal injection of voriconazole or amphotericin B deoxycholate when vitritis or macular involvement is present (Ref). An initial loading dose of 25 mg/kg has also been suggested (Ref).Candidiasis, esophagealCandidiasis, esophageal:Treatment: Infants and Children: Oral, IV: 6 to 12 mg/kg/dose once daily for 14 to 21 days (Ref); maximum dose: 600 mg/dose (Ref). Note: An initial loading dose of 25 mg/kg has also been suggested (Ref).Adolescents: Oral, IV: 6 to 12 mg/kg/dose once daily for 14 to 21 days (Ref); usual adult dose: 400 mg/dose (Ref). Note: An initial loading dose of 25 mg/kg has also been suggested (Ref).Suppressive therapy (secondary prophylaxis): Patients with HIV: Note: Not typically recommended, but can be considered if experiencing frequent severe recurrent infection (Ref).Infants and Children: Oral: 6 to 12 mg/kg/dose three times weekly; maximum dose: 600 mg/dose. If daily administration is required, maximum dose is 200 mg/dose (Ref).Adolescents: Oral: 100 to 200 mg once daily (Ref).Candidiasis, oropharyngealCandidiasis, oropharyngeal:Treatment:Infants and Children: Oral: 6 to 12 mg/kg/dose once daily for 7 to 14 days (Ref); maximum dose: 400 mg/dose (Ref).Adolescents: Oral: 6 mg/kg/dose once daily for 7 to 14 days (Ref); usual adult dose: 100 to 200 mg/dose (Ref).Suppressive therapy (secondary prophylaxis): Patients with HIV: Note: Not typically recommended, but can be considered if experiencing frequent severe recurrent infection (Ref).Infants and Children: Oral: 6 to 12 mg/kg/dose three times weekly; maximum dose: 600 mg/dose. If daily administration is required, maximum dose is 200 mg/dose (Ref).Adolescents: Oral: 100 to 200 mg once daily or three times weekly (Ref).Candidiasis, peritoneal dialysis-related infectionsCandidiasis, peritoneal dialysis-related infections (Ref):Peritonitis: Infants, Children, and Adolescents:Treatment: Intraperitoneal, IV, Oral: 6 to 12 mg/kg/dose every 24 to 48 hours; maximum dose: 400 mg/dose.Prophylaxis for high-risk situations (eg, during antibiotic therapy or PEG placement): IV, Oral: 3 to 6 mg/kg/dose every 24 to 48 hours; maximum dose: 200 mg/dose.Exit-site or tunnel infection, treatment: Infants, Children, and Adolescents: Oral: 6 mg/kg/dose every 24 to 48 hours; maximum dose: 400 mg/dose.Candidiasis, vulvovagin*l infectionCandidiasis, vulvovagin*l infection:Uncomplicated infections, treatment (independent of HIV status): Adolescents: Oral: 150 mg as a single dose (Ref).Severe infections, treatment:Non-HIV-exposed/-infected: Adolescents: Oral: 150 mg every 72 hours for 2 to 3 doses (Ref).HIV-exposed/-infected: Adolescents: Oral: 100 to 200 mg once daily for ≥7 days; may follow with chronic suppressive therapy of 150 mg once weekly (Ref).Recurrent infection, treatment:Non HIV-exposed/-infected: Adolescents: Oral: Initial: 100 to 200 mg every 72 hours for 3 doses; followed by maintenance of 100 to 200 mg once weekly for 6 months (Ref).HIV-exposed/-infected: Adolescents: Oral: 100 to 200 mg once daily for ≥ 7 days; may follow with chronic suppressive therapy of 150 mg once weekly (Ref).Coccidioidomycosis, HIV-exposed/-infectedCoccidioidomycosis, HIV-exposed/-infected (Ref):Mild to moderate non-meningeal infection (eg, focal pneumonia): Infants and Children: IV, Oral: 6 to 12 mg/kg/dose once daily; maximum dose: 400 mg/dose.Adolescents: Oral: 400 mg once daily for ≥6 months.Severe illness (diffuse pulmonary or disseminated non-meningitic disease) initial therapy if unable to use amphotericin or as step-down therapy: Infants and Children: IV, Oral: 12 mg/kg/dose once daily; maximum dose: 800 mg/dose for a total of 1 year of treatment followed by secondary prophylaxis.Meningeal infection:Infants and Children: IV, Oral: 12 mg/kg/dose once daily; maximum dose: 800 mg/dose, followed by lifelong secondary prophylaxis.Adolescents: IV, Oral: 400 to 800 mg once daily, followed by lifelong suppressive therapy.Secondary prophylaxis/chromic suppressive therapy: Infants, Children, and Adolescents: Oral: 6 mg/kg/dose once daily; maximum dose: 400 mg/dose.Cryptococcal infectionCryptococcal infection:Mild to moderate localized infection including pneumonia (not CNS), treatment:Non HIV-exposed/-infected: Infants, Children, and Adolescents: Oral: 6 to 12 mg/kg/dose once daily for 6 to 12 months. Usual adult dose is 400 mg/dose (Ref).HIV-exposed/-infected: Infants and Children: IV, Oral: 12 mg/kg on day 1, then 6 to 12 mg/kg/dose once daily; maximum dose: 600 mg/dose; duration depends on severity and clinical response (Ref).Adolescents: Oral: 400 mg daily for 12 months (Ref).CNS, severe pulmonary or disseminate infection, treatment:Induction therapy: HIV-exposed/-infected (not first-line therapy):Infants and Children: IV: 12 mg/kg on day 1, then 10 to 12 mg/kg/dose once daily in combination with amphotericin B or flucytosine for ≥14 days; maximum dose: 800 mg/dose (Ref).Adolescents: IV, Oral: 400 to 800 mg once daily in combination with flucytosine for ≥14 days or 800 mg once daily in combination with amphotericin for ≥14 days or 1,200 mg once daily as monotherapy for at least 2 weeks (Ref).Consolidation:Non-HIV-exposed/-infected: Infants, Children, and Adolescents: IV, Oral: 10 to 12 mg/kg/day once daily or in divided doses twice daily for 8 weeks; maximum dose: 800 mg/dose (Ref).HIV-exposed/-infected:Infants and Children: IV, Oral: 12 mg/kg on day 1, then 10 to 12 mg/kg/day once daily for ≥8 weeks; maximum daily dose: 800 mg/dose (Ref).Adolescents: IV, Oral: 400 mg once daily for ≥8 weeks (Ref).Secondary prophylaxis/chronic suppressive maintenance therapy: Non-HIV-exposed/-infected: Infants, Children, and Adolescents: Oral: 6 mg/kg/dose once daily for 6 to 12 months; maximum dose: 200 mg/dose (Ref).HIV-exposed/-infected: Infants, Children, and Adolescents: Oral: 6 mg/kg/dose once daily for ≥12 months; maximum dose: 200 mg/dose (Ref).HistoplasmosisHistoplasmosis: HIV-exposed/-infected patients, alternative therapy (Ref):Pulmonary, acute primary disease: Infants and Children: Oral: 3 to 6 mg/kg/dose once daily; maximum dose: 200 mg/dose.Disseminated disease, mild to moderate:Infants and Children: IV, Oral: 5 to 6 mg/kg/dose twice daily for 12 months; maximum dose: 300 mg/dose.Adolescents: Oral: 800 mg once daily.Secondary prophylaxis/chronic suppressive therapy:Infants and Children: Oral: 3 to 6 mg/kg/dose once daily for ≥12 months; maximum dose: 200 mg/dose.Adolescents: Oral: 400 mg once daily for ≥12 months.Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricNote: Dosing is based on pharmaco*kinetic parameters, limited pediatric studies, adult studies, and expert opinion (Ref).Altered kidney function:Infants, Children, and Adolescents (Ref): Note: In critically ill patients with altered kidney function, consider monitoring serum concentrations if available (Ref).CrCl ≥50 mL/minute/1.73 m2: IV, Oral: Administer the usual indication-specific dose every 24 hours.CrCl <50 mL/minute/1.73 m2: IV, Oral: Administer the usual indication-specific dose every 48 hours or administer 100% of the usual indication-specific dose or loading dose initially, followed by 50% of the usual indication-specific dose every 24 hours.Note: No dosage adjustment necessary for single-dose therapy for vagin*l candidiasis (Ref).Hemodialysis, intermittent:Note: Based on adult information, fluconazole is dialyzable (33% to 38% with low-flux dialyzers (Ref) or approximately 50% after a 3-hour session (Ref).Infants, Children, and Adolescents: IV/Oral:Dialysis days: Administer the usual indication-specific dose after each dialysis session (Ref). Note: The manufacturer's labeling recommends that in addition to 100% of the dose given after dialysis on dialysis days, patients should also receive a reduced dose according to their creatinine clearance on nondialysis days; however, based on adult data, this appears unnecessary, as fluconazole concentrations decrease only minimally during the interdialytic period (Ref).Peritoneal dialysis:Infants, Children, and Adolescents: IV, Oral: Administer 50% of the usual indication-specific dose every 24 to 48 hours (Ref).CRRT:Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Flow rates vary widely in pediatric patients. Appropriate dosing requires consideration of drug penetration to site of infection, severity of illness, and consideration of loading dose. Close monitoring of response and adverse reactions due to drug accumulation is important. Due to limited data and patient variability, monitor serum concentrations if available (target AUC24/MIC 50 to 100 or trough concentrations 10 to 15 mg/L [for MICs up to 4 mg/L] in critical illness) (Ref)­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­.CVVH/CVVHD/CVVHDF: Children and Adolescents: IV, Oral: Loading dose: 6 to 12 mg/kg once, followed by 6 to 12 mg/kg/dose (as appropriate for patient-specific indication) every 24 hours; maximum dose: 800 mg/dose. For some indications, a higher initial loading dose may be appropriate (Ref).Note: Fluconazole undergoes substantial tubular reabsorption in patients with normal kidney function. Because this reabsorption is absent in anuric patients receiving renal replacement therapy, total fluconazole clearance in adults receiving CRRT with rates of 1,500 to 3,000 mL/hour is 1.5 to 2.3 times that reported in healthy volunteers (Ref). In one case report in an adolescent receiving CVVH with a high flow rate (4,090 mL/hour), the patient required double the initial dosage (to 20 mg/kg/day) to achieve pharmacodynamic targets (Ref).Dosing: Hepatic Impairment: PediatricThere are no dosage adjustments provided in manufacturer's labeling; use with caution.Dosing: Adult(For additional information see "Fluconazole: Drug information")BlastomycosisBlastomycosis (off-label use):CNS disease (alternative agent): Step-down therapy: Oral: 800 mg once daily for ≥12 months and until resolution of cerebrospinal (CSF) abnormalities (Ref).Pulmonary disease (alternative agent if unable to tolerate itraconazole): Oral: 400 to 800 mg once daily for 6 to 12 months (Ref).Candidiasis, treatmentCandidiasis, treatment: Note: Consider weight-based dosing for patients <50 kg or >90 kg (Ref). A maximum dose has not been established, but based on a small number of patients, doses up to 1.6 g/day appear to be well tolerated (Ref).Candidemia (neutropenic and non-neutropenic patients):Initial therapy (alternative agent):Note: For use in non-neutropenic patients that are not critically ill and not at high risk of fluconazole-resistant isolate. For use in neutropenic patients that are not critically ill and have had no prior azole exposure (Ref); some experts reserve for neutropenic patients who cannot be treated with other agents and whose ANC is >500 and increasing (Ref).IV, Oral: Loading dose of 800 mg (or 12 mg/kg) on day 1, then 400 mg (or 6 mg/kg) once daily; if fluconazole-susceptible Candida glabrata isolated, transition to 800 mg (or 12 mg/kg) once daily (Ref).Step-down therapy:Isolates other than C. glabrata: Oral: 400 mg (or 6 mg/kg) once daily (Ref).Isolates of C. glabrata (if fluconazole-susceptible or susceptible dose-dependent): Oral: 800 mg (or 12 mg/kg) once daily (Ref).Duration: Continue for ≥14 days after first negative blood culture and resolution of signs/symptoms (longer duration required in patients with metastatic complications); step-down therapy to oral fluconazole (eg, after initial therapy with an echinocandin) is recommended after 5 to 7 days in stable patients with negative repeat cultures and fluconazole-susceptible isolates (Ref).Cardiac device infection (eg, implantable cardiac defibrillator, pacemaker, ventricular assist device [VAD]): Step-down therapy: IV, Oral: 400 to 800 mg (or 6 to 12 mg/kg) once daily for 4 to 6 weeks after device removal (4 weeks for infections limited to generator pockets and ≥6 weeks for infections involving wires). Note: If VAD cannot be removed, chronic suppressive therapy with fluconazole 400 to 800 mg (or 6 to 12 mg/kg) once daily should be used (Ref).Chronic, disseminated (hepatosplenic): Step-down therapy: Oral: 400 mg (or 6 mg/kg) once daily; continue until lesion resolution (usually several months) and through periods of immunosuppression (Ref).CNS: Step-down therapy (fluconazole-susceptible isolates): IV, Oral: 400 to 800 mg (or 6 to 12 mg/kg) once daily; continue until signs/symptoms and CSF/radiologic abnormalities have resolved (Ref).Endocarditis, native or prosthetic valve: Step-down therapy (fluconazole-susceptible isolates): IV, Oral: 400 to 800 mg (or 6 to 12 mg/kg) once daily for ≥6 weeks after valve replacement surgery (longer durations recommended in patients with perivalvular abscesses or other complications). Note: In patients who cannot undergo valve replacement surgery or with prosthetic valve endocarditis, chronic suppressive therapy with fluconazole 400 to 800 mg (or 6 to 12 mg/kg) once daily should be used (Ref).Endophthalmitis, endogenous (with or without vitritis) (fluconazole-susceptible isolates): IV, Oral: Loading dose of 800 mg (or 12 mg/kg) on day 1, then 400 to 800 mg (or 6 to 12 mg/kg) once daily for ≥4 to 6 weeks and until examination indicates resolution (longer duration may be needed for patients with vitritis); for patients with vitritis or macular involvement, intravitreal antifungal therapy is also recommended (Ref).Esophageal, treatment: IV, Oral: 400 mg (or 6 mg/kg) on day 1, then 200 to 400 mg (or 3 to 6 mg/kg) once daily for 14 to 21 days (Ref). Some experts increase to 800 mg once daily for those with C. albicans infection who do not respond after 1 week (Ref).Esophageal, chronic suppression for recurrent infection:Note: Suppressive therapy is usually unnecessary. Reserve for immunocompromised patients (eg, with HIV and low CD4 count) who have multiple recurrent infections (Ref).Oral: 100 to 200 mg once daily (Ref). Some experts suggest 100 to 200 mg 3 times weekly (Ref); however, resistance may be a potential concern (Ref). May discontinue once immune reconstitution occurs (Ref).Intertrigo, refractory to topical therapy (off-label use): Oral: 150 mg once weekly for 4 weeks (Ref).Intra-abdominal infection, acute, including peritonitis and/or abscess (alternative agent):Note: For empiric therapy, reserve as an alternative to an echinocandin if no previous azole exposure, noncritically ill, and not at high risk of fluconazole-resistant isolate (Ref). Step-down therapy (after patient has responded to initial therapy [eg, echinocandin]) with fluconazole is recommended in stable patients with a fluconazole-susceptible isolate (Ref).IV, Oral: 800 mg (or 12 mg/kg) on day 1, then 400 mg (or 6 mg/kg) once daily. Total antifungal duration is ≥14 days based on source control and clinical response (Ref).Oropharyngeal: Note: Reserve use for moderate to severe disease, poor response to topical treatment, or recurrent infection (Ref).IV, Oral: 200 mg on day 1, then 100 to 200 mg once daily for 7 to 14 days (Ref); some experts increase to 400 mg once daily for those who do not initially respond (Ref).Oropharyngeal, chronic suppression for recurrent infection: Note: Suppressive therapy is usually unnecessary. Reserve for immunocompromised patients (eg, with HIV and low CD4 count) who have multiple recurrent infections (Ref).Oral: 100 mg once daily (Ref). Some experts suggest 100 mg 3 times weekly (Ref); however, resistance may be a potential concern (Ref). May discontinue once immune reconstitution occurs (Ref).Osteoarticular (osteomyelitis or septic arthritis) (fluconazole-susceptible isolates): Initial or step-down therapy: IV, Oral: 400 mg (or 6 mg/kg) once daily. Duration for osteomyelitis is 6 to 12 months and for septic arthritis is 6 weeks. Course may include 2 weeks of initial treatment with a lipid formulation of amphotericin B or an echinocandin. For prosthetic joints that cannot be removed, chronic suppressive therapy with fluconazole 400 mg (or 6 mg/kg) once daily is recommended (Ref).Peritonitis, associated with peritoneal dialysis: Note: Use for empiric treatment if no prior azole exposure or for directed therapy against fluconazole-susceptible isolates (Ref):IV, Oral: 200 mg on day 1, then 100 to 200 mg once daily for 2 to 4 weeks (Ref).Thrombophlebitis, suppurative: Initial or step-down therapy: IV, Oral: 400 to 800 mg (or 6 to 12 mg/kg) once daily for ≥2 weeks after candidemia (if present) has cleared (Ref).Urinary tract infection:Candiduria (asymptomatic):Patients with neutropenia: Treat as if patient has candidemia (Ref).Patients undergoing a urologic procedure: Oral: 400 mg (or 6 mg/kg) once daily several days before and after the procedure (Ref).Cystitis (symptomatic): Oral: 200 mg (or 3 mg/kg) once daily for 2 weeks (Ref).Pyelonephritis: Oral: 200 to 400 mg (or 3 to 6 mg/kg) once daily for 2 weeks (Ref).Urinary tract infection associated with fungus balls: Oral: 200 to 400 mg (or 3 to 6 mg/kg) once daily; concomitant amphotericin B deoxycholate irrigation via nephrostomy tubes, if present, is also recommended, along with surgical management (Ref).Vulvovagin*l: Note: Not recommended for infection due to C. glabrata or C. krusei (Ref).Mild or moderate infection in immunocompetent patient: Oral: 150 mg as a single dose (Ref).Severe infection or infection in immunocompromised patient: Oral: 150 mg every 72 hours for 2 or 3 doses (Ref).Recurrent infection:Fluconazole monotherapy: Oral: 150 mg every 72 hours for 10 to 14 days, followed by 150 mg once weekly for 6 months (Ref) or 100 mg, 150 mg, or 200 mg every 72 hours for 3 doses, then 100 mg, 150 mg, or 200 mg once weekly for 6 months (Ref).Combination therapy with oteseconazole: Oral:Days 1 to 7: Fluconazole 150 mg as a single dose on days 1, 4, and 7 (Ref).Days 14 to 20: Oteseconazole 150 mg once daily (Ref).Starting on day 28: Oteseconazole 150 once weekly for 11 weeks (Ref).Candidiasis, prophylaxisCandidiasis, prophylaxis:Hematologic malignancy patients (off-label use) or hematopoietic cell transplant (HCT) recipients who do not warrant mold-active prophylaxis (off-label use): Oral: 400 mg once daily. Duration is at least until resolution of neutropenia and/or through day 75 in allogeneic HCT recipients (Ref).ICU patients (high risk) in units with a high rate (>5%) of invasive candidiasis (off-label use): Oral, IV: Loading dose of 800 mg (or 12 mg/kg) once on day 1, then 400 mg (or 6 mg/kg) once daily (Ref).Peritoneal dialysis-associated infection (concurrently treated with antibacterials), prevention of secondary fungal infection: Oral: 200 mg every other day or 100 mg once daily (Ref).Solid organ transplant recipients (selected patients at high-risk for Candida infection) (off-label use): Oral, IV: 400 mg (or 6 mg/kg) given perioperatively and continued once daily postoperatively; indications and duration vary among transplant centers (Ref).Coccidioidomycosis, treatmentCoccidioidomycosis, treatment (off-label use):Bone and/or joint infection: Initial or step-down therapy: Oral: 800 mg once daily for ≥3 years; in some cases, lifelong treatment is needed; duration depends on severity and host immunocompetence (Ref).Meningitis: Oral: 400 mg to 1.2 g once daily, depending on severity (Ref); some experts favor a starting dose of ≥800 mg once daily (Ref). Continue lifelong as there is a high relapse rate when the dose is decreased or treatment is discontinued (Ref).Pneumonia, primary infection: Note: Only for patients with significantly debilitating illness, extensive pulmonary involvement, concurrent diabetes, frailty due to age or comorbidities, or HIV (Ref):Oral: Usual dose: 400 mg once daily; IDSA guidelines state that some experts recommend 800 mg once daily. Duration of therapy is 3 to 6 months for immunocompetent patients; immunocompromised patients require a longer duration of therapy (sometimes lifelong) (Ref).Pneumonia, symptomatic chronic cavitary and/or cavitary disease in immunocompromised patients: Oral: 400 mg once daily for ≥12 months. In patients with ruptured cavities, the duration may be shorter, but depends upon the postoperative course (Ref).Soft tissue infection (not associated with bone infection): Oral: 400 mg once daily; some experts give up to 800 mg once daily; duration is for ≥6 to 12 months (Ref).Coccidioidomycosis, prophylaxisCoccidioidomycosis, prophylaxis (off-label use):Patients with HIV: Note: Primary prophylaxis is not recommended; yearly or twice-yearly serologic testing should be performed in patients living in endemic areas.Patients with a CD4 count <250 cells/mm3 who have a new positive serology: Oral: 400 mg once daily until antiretroviral therapy has fully suppressed HIV replication and the CD4 count is ≥250 cells/mm3 (Ref).Solid organ transplant recipients:Seronegative patients in endemic areas (regardless of clinical history of coccidioidomycosis): Oral: 200 mg once daily for 6 to 12 months following transplantation (Ref); some experts favor 400 mg once daily (Ref).Seropositive patients in endemic areas: Oral: 400 mg once daily for 6 to 12 months following transplantation (Ref); some experts favor 400 mg once daily for 12 months posttransplantation followed by 200 mg once daily for the duration of immunosuppressive therapy (Ref).Cryptococcal meningitisCryptococcal meningitis:Patients with HIV:Induction: Note: Induction therapy should be continued beyond the durations listed below if clinical improvement is not observed and/or if CSF cultures remain positive (Ref).Resource-rich settings, alternative regimens:If flucytosine is unavailable or not tolerated: Oral: 800 mg to 1.2 g once daily in combination with amphotericin B (lipid formulation preferred) for ≥2 weeks (Ref).If amphotericin B is unavailable or not tolerated: Oral: 800 mg to 1.2 g once daily in combination with flucytosine for ≥2 weeks (Ref).If flucytosine and amphotericin B are unavailable or not tolerated: Oral: 1.2 g once daily as monotherapy for ≥2 weeks (Ref).Resource-limited settings:Oral: 1.2 g once daily for 2 weeks in combination with flucytosine and a single dose of liposomal amphotericin B (preferred regimen) (Ref).If liposomal amphotericin B is not available: Oral: 1.2 g once daily for 1 week, started after completion of 1 week of amphotericin B deoxycholate in combination with flucytosine (Ref).If no amphotericin B formulation is available: Oral: 1.2 g once daily in combination with flucytosine for 2 weeks (Ref).If flucytosine is unavailable: Oral: 1.2 g once daily in combination with liposomal amphotericin B or amphotericin B deoxycholate for 2 weeks (Ref).Consolidation: Oral: 800 mg once daily for ≥8 weeks; may consider reducing dose to 400 mg once daily in patients who are treated with amphotericin B and flucytosine induction regimen, have negative CSF cultures after 2 weeks of induction therapy, and are initiated on antiretroviral therapy (Ref).Maintenance (suppression): Oral: 200 mg once daily for ≥12 months; may discontinue if completed induction, consolidation, and ≥12 months of maintenance therapy, patient remains asymptomatic, and CD4 count has been ≥100 cells/mm3 for ≥3 months and HIV RNA is suppressed in response to effective antiretroviral therapy (Ref).HIV-uninfected patients:Induction (alternative regimens):If flucytosine is unavailable or not tolerated: Oral: 800 mg once daily in combination with amphotericin B for 2 weeks (Ref).If amphotericin B is unavailable or not tolerated: Oral: 800 mg to 1.2 g once daily in combination with flucytosine for 2 to 10 weeks, depending on severity and response to therapy (Ref).If amphotericin B and flucytosine are unavailable or not tolerated: Oral: 1.2 g once daily as monotherapy for ≥10 weeks (Ref).Consolidation: Oral: 400 to 800 mg once daily for 8 weeks (some experts prefer 800 mg once daily for patients who receive a 2-week induction course) (Ref).Maintenance (suppression): Oral: 200 to 400 mg once daily for 6 to 12 months (Ref). A longer duration may be warranted for patients receiving very high doses of immunosuppression (eg, high-dose steroids or biologic agents [eg, alemtuzumab]) or with radiographic evidence of cryptococcoma (Ref).Cryptococcosis, pulmonary infectionCryptococcosis, pulmonary infection (off-label use):Mild to moderate symptoms (if severe pneumonia, treat like CNS infection): Immunocompetent or immunocompromised patients without diffuse pulmonary infiltrates or disseminated infection: Oral: 400 mg once daily for 6 to 12 months (Ref); for patients with HIV, some experts recommend 400 to 800 mg once daily for 10 weeks, followed by 200 mg once daily for a total of 6 months in combination with effective antiretroviral therapy (Ref). Chronic suppressive therapy may be warranted for patients with ongoing immunosuppression (Ref).OnychomycosisOnychomycosis (alternative agent) (off-label use):Note: For patients unable to use preferred agents (Ref).Oral: 150 to 450 mg once weekly. Usual duration of therapy: 3 months (fingernail) or 6 to 12 months (toenail) (Ref).Tinea infectionsTinea infections (alternative agent) (off-label use): Note: For disease that is extensive or refractory to topical therapy (Ref).Tinea corporis/tinea cruris: Oral: 150 to 200 mg once weekly for 2 to 4 weeks (Ref).Tinea pedis/tinea manuum: Oral: 150 mg once weekly for 2 to 6 weeks (Ref).Tinea versicolor: Oral: 300 mg once weekly for 2 weeks (Ref).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultThe renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.Altered kidney function: Note: Renal function estimated using the co*ckcroft-Gault formula.No adjustment for vagin*l candidiasis single-dose therapy.For multiple dosing, administer 100% of the indication-specific loading/initial dose recommended in the adult dosing section, then adjust daily doses as follows: IV, Oral (Ref):CrCl >50 mL/minute: No dosage adjustment necessary.CrCl ≤50 mL/minute: Reduce dose by 50%.Hemodialysis, intermittent (thrice weekly): IV, Oral: Dialyzable (33% to 38% with low-flux dialyzers (Ref):Three-times-weekly (postdialysis) dosing: No dosage adjustment necessary for indication-specific loading/initial or maintenance dose recommended in the adult dosing section; however, only administer maintenance doses 3 times/week (on dialysis days) after the dialysis session (Ref).Note: The manufacturer's labeling recommends that in addition to 100% of the dose given after dialysis on dialysis days, patients should also receive a reduced dose according to their creatinine clearance on nondialysis days; however, this appears unnecessary, as fluconazole concentrations decrease only minimally during the interdialytic period (Ref).Once-daily dosing (may be considered when a more convenient dosing regimen is preferred [eg, hospitalized patients]): Administer 100% of the indication-specific loading/initial dose recommended in the adult dosing section, then reduce maintenance dose by 50% and administer once daily; when scheduled dose falls on a dialysis day, administer after dialysis (Ref).Peritoneal dialysis:IV, Oral: Initial: Administer 100% of the indication-specific loading/initial dose recommended in the adult dosing section; reduce maintenance doses by 50% (Ref).CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour), unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions due to drug accumulation is important.CVVH/CVVHD/CVVHDF: IV, Oral:If the usual recommended dose is 200 mg once daily, administer 400 mg once daily (Ref) (see note regarding increased clearance in patients receiving renal replacement therapy below).If the usual recommended dose is 400 mg once daily, administer an 800 mg loading dose, followed by maintenance doses of 800 mg/day in 1 to 2 divided doses (Ref).If the usual recommended dose is 800 mg once daily, administer a 1.2 g loading dose, followed by maintenance doses of 1.2 g/day in 1 to 2 divided doses (Ref) (see note regarding increased clearance in patients receiving renal replacement therapy below).Note: Fluconazole undergoes substantial tubular reabsorption in patients with normal kidney function. Because this reabsorption is absent in anuric patients receiving renal replacement therapy, total fluconazole clearance during CRRT with rates of 1,500 to 3,000 mL/hour is 1.5 to 2.3 times that reported in healthy volunteers (Ref).PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions due to drug accumulation is important.PIRRT (effluent flow rate 4 to 5 L/hour, 8- to 10-hour session given every day):IV, Oral:Loading dose:Administer 100% of the recommended indication-specific loading dose recommended in the adult dosing section.Maintenance dose: Note: Optimal dose not well established. Select dose based on pathogen, minimum inhibitory concentration, immunocompromised state, and disease severity.400 mg once (Ref) or twice daily (Ref).Dosing: Hepatic Impairment: AdultThere are no dosage adjustments provided in the manufacturer's labeling; use with caution.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.[DSC] = Discontinued productSolution, Intravenous: Generic: 200 mg (100 mL); 200 mg/100 mL in NaCl 0.9% (100 mL); 400 mg (200 mL)Solution, Intravenous [preservative free]: Generic: 100 mg/50 mL in NaCl 0.9% (50 mL); 200 mg (100 mL [DSC]); 200 mg/100 mL in NaCl 0.9% (100 mL); 400 mg (200 mL); 400 mg/200 mL in NaCl 0.9% (200 mL)Suspension Reconstituted, Oral: Diflucan: 10 mg/mL (35 mL); 40 mg/mL (35 mL) [orange flavor]Generic: 10 mg/mL (35 mL); 40 mg/mL (35 mL)Tablet, Oral: Diflucan: 50 mg [DSC], 100 mg, 150 mg, 200 mg [contains fd&c red #40(allura red ac)aluminum lake]Generic: 50 mg, 100 mg, 150 mg, 200 mgGeneric Equivalent Available: USYesDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution, Intravenous: Diflucan: 2-0.9 MG/ML-% (100 mL)Generic: 2-0.9 MG/ML-% (100 mL)Suspension Reconstituted, Oral: Diflucan: 10 mg/mL (35 mL) [contains sodium benzoate]Tablet, Oral: Generic: 50 mg, 100 mg, 200 mgAdministration: PediatricOral: Administer without regard to meals; shake suspension well before use.Parenteral: Do not use if cloudy or precipitated. Administered by IV infusion over approximately 1 to 2 hours at a rate not to exceed 200 mg/hour. The following infusion times were described in pediatric clinical trials:Neonatal: Loading doses (25 mg/kg) have been infused over 2 hours (Ref); doses ranging from 3 to 12 mg/kg/dose have been infused over 1 to 2 hours including extremely low birth weight neonates (Ref).Pediatric: Doses up to 8 to 10 mg/kg were infused over 2 hours (Ref).Administration: AdultIV: Do not use if cloudy or precipitated. Infuse over ~1 to 2 hours; do not exceed 200 mg/hour.Oral: May be administered without regard to meals.Hazardous Drugs Handling ConsiderationsHazardous agent (NIOSH 2016 [group 3]).Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.NIOSH recommends single gloving for administration of intact tablets or capsules. NIOSH recommends double gloving, a protective gown, and (if there is a potential for vomit or spit up) eye/face protection for administration of an oral liquid/feeding tube administration. For IV compounding, double gloves, a protective gown, ventilated engineering controls (a class II biological safety cabinet or a compounding aseptic containment isolator), and closed system transfer devices (CSTDs) are recommended. Double gloving and a gown are required during IV administration (NIOSH 2016). Premixed solutions may be excluded from some hazardous drug handling requirements. Assess risk to determine appropriate containment strategy (USP-NF 2017).Storage/StabilityTablet: Store at <30°C (86°F).Powder for oral suspension: Store dry powder at <30°C (86°F). Following reconstitution, store at 5°C to 30°C (41°F to 86°F). Discard unused portion after 2 weeks. Do not freeze. Injection: Store injection in glass at 5°C to 30°C (41°F to 86°F). Store injection in plastic flexible containers with overwrap at 20°C to 25°C (68°F to 77°F). Do not freeze. Do not unwrap unit until ready for use.UseTreatment of candidiasis (vagin*l, oropharyngeal, esophageal, urinary tract infections, peritonitis, pneumonia, and systemic infections); cryptococcal meningitis; antifungal prophylaxis in allogeneic bone marrow transplant recipients (All indications: FDA approved in all ages); has also been used as prophylaxis and treatment of peritonitis and treatment of exit-site and tunnel infections in patients with peritoneal dialysis catheters.Medication Safety IssuesSound-alike/look-alike issues: Fluconazole may be confused with flecainide, FLUoxetine, furosemide, itraconazole, voriconazoleDiflucan may be confused with diclofenac, Diprivan, disulfiramInternational issues:Canesten (oral capsules) [Great Britain] may be confused with Canesten brand name for clotrimazole (various dosage forms) [multiple international markets]; Cenestin brand name estrogens (conjugated A/synthetic) [US, Canada] Adverse Reactions (Significant): ConsiderationsCardiovascular effectsDysrhythmias: Azole antifungals, including fluconazole, have been associated with prolonged QT interval on ECG, which may lead to torsades de pointes (TdP) or polymorphic ventricular arrhythmias. Numerous probable cases of TdP have been reported with fluconazole in patients with additional risk factors (Ref). Drug-drug interactions commonly play a role in risk related to cardiac effects with fluconazole either by an additive pharmacodynamic effect, reducing the clearance of fluconazole, or by lowering potassium and/or magnesium concentrations (Ref).Vascular: Another rare cardiac effect with fluconazole is hypersensitivity coronary syndrome (ie, allergic angina or Kounis syndrome) (Ref).Mechanism:Dysrhythmias: One proposed mechanism is that azole antifungals may block the IKr channel (Ref). Another possible mechanism is depression of rapidly activating delayed rectifier potassium channels (Ref).Vascular: Kounis syndrome is thought to be caused by an allergen mediated-IgE and mast cell activation and degranulation causing histamine release (Ref).Onset:Dysrhythmias: Rapid; QT prolongation occurred within the first 24 hours to a couple of days after initiation, dependent on drug-drug interactions (Ref).Vascular: Kounis syndrome may occur immediately after the first dose (Ref).Risk factors:Drug-induced QTc prolongation/TdP (in general):• Females (Ref)• Age >65 years (Ref)• Structural heart disease (eg, history of myocardial infarction or heart failure with reduced ejection fraction) (Ref)• Genetic defects of cardiac ion channels (Ref)• History of drug-induced TdP (Ref)• Congenital long QT syndrome (Ref)• Longer baseline QTc interval (eg, >450 msec) or lengthening of the QTc by ≥60 msec (Ref)• Electrolyte disturbances (eg, hypocalcemia, hypokalemia, hypomagnesemia) (Ref)• Bradycardia (Ref)• Hepatic impairment (Ref)• Kidney impairment (Ref)• Diuretic use (Ref)• Sepsis (Ref)• Concurrent administration of multiple medications (≥2) that prolong the QT interval or medications with drug interactions that increase serum concentrations of QT-prolonging medications (Ref)Dermatologic reactionsDermatologic reactions are usually mild and include maculopapular skin rash (Ref), fixed drug eruption (FDE) (Ref), alopecia (Ref) and symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) (Ref). Rare reports of severe cutaneous adverse reactions (SCARs) include Stevens-Johnson syndrome (SJS) (Ref), toxic epidermal necrolysis (TEN) (Ref), drug reaction with eosinophilia and systemic symptoms (DRESS) (Ref), and acute generalized exanthematous pustulosis (AGEP) (Ref). Other cutaneous reactions include Sweet’s syndrome (Ref).Mechanism: Non–dose-related; immunologic. Maculopapular eruptions, FDE, SDRIFE, and SCARs are T-cell-mediated (Ref).Onset: Delayed hypersensitivity reactions: Varied. Maculopapular rash usually occurs 5 to 21 days after start of therapy (Ref), although can occur after 1 dose, especially in previously sensitized patients (Ref). FDE lesions can develop within 15 minutes to 2 days after drug administration (Ref). SCARs usually occur 1 to 8 weeks after initiation (Ref); reexposure may lead to more rapid onset (usually within 1 to 4 days) (Ref).Risk factors:• Cross-reactivity: Cross-reactivity among oral azole antifungals has not been consistently reported. Possible cross-reactivity between fluconazole and itraconazole has been suggested (Ref). However, lack of cross-reactivity has been documented between fluconazole and itraconazole, as well as between fluconazole and ketoconazole (Ref). In addition, no cross-reactivity was noted between fluconazole and voriconazole (Ref).HepatotoxicityAzole antifungals, including fluconazole, may cause hepatotoxicity (ranging from mild and asymptomatic liver abnormalities to hepatic failure) (Ref). From a 2010 meta-analysis, fluconazole users had increased serum transaminases that did not require discontinuation (Ref). Hepatotoxicity may also occur as part of drug rash eosinophilia with systemic symptoms (DRESS) (Ref). Fluconazole liver injury is usually hepatocellular hepatitis, but may present as cholestatic hepatitis or hepatitis (mixed) (Ref). Most cases of hepatotoxicity are self-limited; although, recovery may take up to 3 to 4 months (Ref).Mechanism: Not well known; possible mechanisms include mitochondrial dysfunction, idiosyncratic, and immunologic (Ref).Onset: Varied; most cases occur within 1 to 2 months of initiation (Ref).Risk factors:• Fluconazole-induced liver injury has been reported as both dose- and non–dose-dependent (Ref)• Preexisting liver disease (Ref)• Concurrent hepatotoxic agents and drug interactions (Ref)• Kidney impairment (Ref)• HIV (Ref)• Cross-reactivity among oral azole antifungals has not been consistently reported in patients with histories of hepatotoxicity (Ref)• Acute liver injury is less common with fluconazole than other azoles (voriconazole, posaconazole) (Ref)Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.>10%: Nervous system: Headache (adults: 2% to 13%)1% to 10%:Dermatologic: Skin rash (adults: 2%)Gastrointestinal: Abdominal pain (2% to 6%), diarrhea (2% to 3%), dysgeusia (adults: 1%), dyspepsia (adults: 1%), nausea (adults: 4% to 7%; children and adolescents: 2%), vomiting (2% to 5%)Nervous system: Dizziness (adults: 1%)Frequency not defined: Hepatic: Increased serum alkaline phosphatasePostmarketing:Cardiovascular: Prolonged QT interval on ECG, torsades de pointes (Poluzzi 2010)Dermatologic: Acute generalized exanthematous pustulosis (Alsadhan 2002; Di Lernia 2015), alopecia (Pappas 1995), diaphoresis, exfoliative dermatitis, Stevens-Johnson syndrome (Craythorne 2009, Monastirli 2008), Sweet’s syndrome (Adler 2018), toxic epidermal necrolysis (George 2012, Islam 2014)Endocrine & metabolic: Hypercholesterolemia, hypertriglyceridemia, hypokalemiaGastrointestinal: XerostomiaHematologic & oncologic: Agranulocytosis (Murakami 1992), leukopenia, neutropenia, thrombocytopenia (Murakami 1992)Hepatic: Cholestatic hepatitis (Joseph 2019), hepatic failure (Gayam 2018), hepatitis (mixed) (Joseph 2019), hepatocellular hepatitis (Joseph 2019), hepatotoxicity (Kyriakidis 2017, Song 2005), increased serum transaminases (Wang 2010)Hypersensitivity: Anaphylaxis (Neuhaus 1991), angioedema, fixed drug eruption (Nakai 2013, Quint 2019)Immunologic: Drug reaction with eosinophilia and systemic symptoms (Benjamin Lash 2016, Su 2003)Nervous system: Drowsiness, fatigue, insomnia, malaise, paresthesia, seizure, vertigoNeuromuscular & skeletal: Asthenia, myalgia, tremorMiscellaneous: FeverContraindicationsHypersensitivity to fluconazole or any component of the formulation (cross-reaction with other azole antifungal agents may occur, but has not been established; use caution); coadministration with CYP3A4 substrates, which may lead to QTc prolongation (eg, erythromycin, pimozide, quinidine).Warnings/PrecautionsConcerns related to adverse effects:• CNS effects: May occasionally cause dizziness or seizures; use caution driving or operating machinery.Disease-related concerns:• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment may be necessary.Dosage form specific issues:• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP 1997; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.• Sucrose: Oral suspension contains sucrose; avoid use in patients with fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency.Metabolism/Transport EffectsInhibits CYP2C19 (strong), CYP2C9 (moderate), CYP3A4 (moderate)Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions programAbemaciclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Abemaciclib.Management: Monitor for increased abemaciclib toxicities if combined with moderate CYP3A4 inhibitors. Consider reducing the abemaciclib dose in 50 mg decrements if necessary. Risk C: Monitor therapyAbrocitinib: Fluconazole may increase the serum concentration of Abrocitinib.Risk X: Avoid combinationAcalabrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Acalabrutinib.Management: Reduce acalabrutinib dose to 100 mg once daily with concurrent use of a moderate CYP3A4 inhibitor. Monitor patient closely for both acalabrutinib response and evidence of adverse effects with any concurrent use. Risk D: Consider therapy modificationAlfentanil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Alfentanil.Management: If use of alfentanil and moderate CYP3A4 inhibitors is necessary, consider dosage reduction of alfentanil until stable drug effects are achieved. Frequently monitor patients for respiratory depression and sedation when these agents are combined. Risk D: Consider therapy modificationAlfuzosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Alfuzosin.Risk C: Monitor therapyAlitretinoin (Systemic): CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Alitretinoin (Systemic).Management: Consider reducing the alitretinoin dose to 10 mg when used together with moderate CYP2C9 inhibitors. Monitor for increased alitretinoin effects/toxicities if combined with a moderate CYP2C9 inhibitor. Risk D: Consider therapy modificationALPRAZolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ALPRAZolam.Management: Consider alternatives to this combination when possible. If combined, consider an alprazolam dose reduction and monitor for increased alprazolam effects and toxicities (eg, sedation, lethargy). Risk D: Consider therapy modificationAmiodarone: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Amiodarone. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Amiodarone.Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modificationAmisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapyAmitriptyline: May enhance the QTc-prolonging effect of Fluconazole. Fluconazole may increase the serum concentration of Amitriptyline. Risk C: Monitor therapyAmLODIPine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of AmLODIPine.Risk C: Monitor therapyAmphotericin B: Antifungal Agents (Azole Derivatives, Systemic) may diminish the therapeutic effect of Amphotericin B.Risk C: Monitor therapyApixaban: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Apixaban.Risk C: Monitor therapyAprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Aprepitant.Risk X: Avoid combinationARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole.Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapyARIPiprazole Lauroxil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole Lauroxil.Risk C: Monitor therapyAstemizole: Fluconazole may enhance the QTc-prolonging effect of Astemizole. Fluconazole may increase the serum concentration of Astemizole.Risk X: Avoid combinationAsunaprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Asunaprevir.Risk X: Avoid combinationAtazanavir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Atazanavir.Risk C: Monitor therapyAtogepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Atogepant.Risk C: Monitor therapyAtorvastatin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Atorvastatin.Risk C: Monitor therapyAvacopan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avacopan.Risk C: Monitor therapyAvanafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avanafil.Management: The maximum avanafil dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects (eg, hypotension, syncope, priapism). Risk D: Consider therapy modificationAvapritinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avapritinib.Management: Avoid use of moderate CYP3A4 inhibitors with avapritinib. If this combination cannot be avoided, reduce the avapritinib dose to 100 mg daily for the treatment of GIST or to 50 mg daily for the treatment of advanced systemic mastocytosis. Risk D: Consider therapy modificationAvatrombopag: Fluconazole may increase the serum concentration of Avatrombopag.Management: For chronic immune thrombocytopenia, reduce initial avatrombopag dose to 20 mg 3 times per week. No dosage reduction needed for patients with chronic liver disease-associated thrombocytopenia using altrombopag prior to a procedure. Risk D: Consider therapy modificationAxitinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Axitinib.Risk C: Monitor therapyBarnidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Barnidipine.Risk C: Monitor therapyBelzutifan: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Belzutifan.Risk C: Monitor therapyBenidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Benidipine.Risk C: Monitor therapyBenzhydrocodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased.Risk C: Monitor therapyBlonanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Blonanserin.Risk C: Monitor therapyBortezomib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bortezomib.Risk C: Monitor therapyBosentan: Fluconazole may increase the serum concentration of Bosentan.Risk X: Avoid combinationBosutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib.Risk X: Avoid combinationBrexpiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole.Management: The brexpiprazole dose should be reduced to 25% of usual if used together with both a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Risk C: Monitor therapyBrigatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brigatinib.Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inhibitors when possible. If such a combination cannot be avoided, reduce the dose of brigatinib by approximately 40% (ie, from 180 mg to 120 mg, from 120 mg to 90 mg, or from 90 mg to 60 mg). Risk D: Consider therapy modificationBrivaracetam: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Brivaracetam.Risk C: Monitor therapyBromocriptine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bromocriptine.Management: The bromocriptine dose should not exceed 1.6 mg daily with use of a moderate CYP3A4 inhibitor. The Cycloset brand specifically recommends this dose limitation, but other bromocriptine products do not make such specific recommendations. Risk D: Consider therapy modificationBudesonide (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Oral Inhalation).Risk C: Monitor therapyBudesonide (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic).Management: Avoid the concomitant use of CYP3A4 inhibitors and oral budesonide. If patients receive both budesonide and CYP3A4 inhibitors, they should be closely monitored for signs and symptoms of corticosteroid excess. Risk D: Consider therapy modificationBudesonide (Topical): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Topical).Risk X: Avoid combinationBuprenorphine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Buprenorphine.Risk C: Monitor therapyBusPIRone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of BusPIRone.Risk C: Monitor therapyCabozantinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cabozantinib.Risk C: Monitor therapyCannabis: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol serum concentrations may be increased.Risk C: Monitor therapyCannabis: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased.Risk C: Monitor therapyCarBAMazepine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of CarBAMazepine.Risk C: Monitor therapyCariprazine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Cariprazine. Specifically, concentrations of didesmethylcariprazine (DDCAR), the primary active metabolite of cariprazine, may increase. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cariprazine.Risk C: Monitor therapyCarisoprodol: CYP2C19 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Carisoprodol. CYP2C19 Inhibitors (Strong) may increase the serum concentration of Carisoprodol.Risk C: Monitor therapyCarvedilol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased.Risk C: Monitor therapyCelecoxib: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Celecoxib.Risk C: Monitor therapyCeritinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Ceritinib. Ceritinib may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Ceritinib.Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyCilostazol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cilostazol.Management: Decrease the dose of cilostazol to 50 mg twice daily when combined with moderate CYP3A4 inhibitors. Risk D: Consider therapy modificationCisapride: Fluconazole may enhance the QTc-prolonging effect of Cisapride. Fluconazole may increase the serum concentration of Cisapride.Risk X: Avoid combinationCitalopram: Fluconazole may enhance the QTc-prolonging effect of Citalopram. Fluconazole may increase the serum concentration of Citalopram.Management: Limit citalopram dose to a maximum of 20 mg/day if used with fluconazole, which is a strong CYP2C19 inhibitor. Patients using this combination should be monitored closely for citalopram toxicities, including serotonin syndrome and QT prolongation. Risk D: Consider therapy modificationClindamycin (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Clindamycin (Systemic).Risk C: Monitor therapyCloBAZam: CYP2C19 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of CloBAZam. CYP2C19 Inhibitors (Strong) may increase the serum concentration of CloBAZam.Risk C: Monitor therapyClopidogrel: CYP2C19 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Clopidogrel.Management: Consider alternatives to this combination whenever possible. If such a combination must be used, monitor patients closely for evidence of a diminished response to clopidogrel. Risk D: Consider therapy modificationCobimetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cobimetinib.Management: Avoid this combination when possible. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose from 60 mg to 20 mg daily. Avoid concomitant use in patients already receiving reduced cobimetinib doses. Risk D: Consider therapy modificationCodeine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Codeine.Risk C: Monitor therapyColchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine.Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. See interaction monograph for details. Use extra caution in patients with impaired renal and/or hepatic function. Risk D: Consider therapy modificationConivaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Conivaptan.Risk C: Monitor therapyCopanlisib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Copanlisib.Risk C: Monitor therapyCrizotinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Crizotinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Crizotinib.Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyCyclophosphamide: Fluconazole may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, serum bilirubin and serum creatinine may be increased. Fluconazole may increase the serum concentration of Cyclophosphamide.Risk C: Monitor therapyCycloSPORINE (Systemic): Fluconazole may increase the serum concentration of CycloSPORINE (Systemic).Risk C: Monitor therapyDabigatran Etexilate: Fluconazole may enhance the anticoagulant effect of Dabigatran Etexilate.Risk C: Monitor therapyDabrafenib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Dabrafenib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Dabrafenib.Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and dabrafenib adverse effects when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyDapoxetine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dapoxetine.Management: The dose of dapoxetine should be limited to 30 mg per day when used together with a moderate inhibitor of CYP3A4. Risk D: Consider therapy modificationDaridorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Daridorexant.Management: Limit the daridorexant dose to 25 mg, no more than once per night, when combined with moderate CYP3A4 inhibitors. Risk D: Consider therapy modificationDarifenacin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Darifenacin.Risk C: Monitor therapyDeflazacort: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Deflazacort.Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. Risk D: Consider therapy modificationDexAMETHasone (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DexAMETHasone (Systemic).Risk C: Monitor therapyDexlansoprazole: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Dexlansoprazole.Risk C: Monitor therapyDiazePAM: CYP2C19 Inhibitors (Strong) may increase the serum concentration of DiazePAM.Risk C: Monitor therapyDichlorphenamide: Antifungal Agents (Azole Derivatives, Systemic) may enhance the hypokalemic effect of Dichlorphenamide.Risk C: Monitor therapyDiclofenac (Systemic): CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Diclofenac (Systemic).Risk C: Monitor therapyDilTIAZem: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DilTIAZem.Risk C: Monitor therapyDOCEtaxel: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOCEtaxel.Risk C: Monitor therapyDomperidone: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Domperidone. Risk X: Avoid combinationDOXOrubicin (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional).Risk X: Avoid combinationDronabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Dronabinol.Risk C: Monitor therapyDronabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dronabinol.Risk C: Monitor therapyDronedarone: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Dronedarone. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Dronedarone.Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modificationEbastine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ebastine.Risk C: Monitor therapyElbasvir and Grazoprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Elbasvir and Grazoprevir.Risk C: Monitor therapyEletriptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eletriptan.Risk X: Avoid combinationElexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor.Management: When combined with moderate CYP3A4 inhibitors, twoelexacaftor/tezacaftor/ivacaftor (100 mg/50 mg/75 mg) tablets should be given in the morning, every other day. Ivacaftor (150 mg) should be given in the morning, every other day on alternate days. Risk D: Consider therapy modificationEliglustat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eliglustat.Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with moderate CYP3A4 inhibitors. Avoid use of moderate CYP3A4 inhibitors in CYP2D6 IMs or PMs. Use in CYP2D6 EMs or IMs also taking strong or moderate CYP2D6 inhibitors is contraindicated. Risk D: Consider therapy modificationEncorafenib: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Encorafenib. Management: Avoid use of encorafenib and moderate CYP3A4 inhibitors when possible. If combined, decrease encorafenib dose from 450 mg to 225 mg; 300 mg to 150 mg; and 225 mg or 150 mg to 75 mg. Monitor closely for QT interval prolongation. Risk D: Consider therapy modificationEntrectinib: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Entrectinib. Risk X: Avoid combinationEplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone.Management: If coadministered with moderate CYP3A4 inhibitors, the max dose of eplerenone is 25 mg daily if used for heart failure; if used for hypertension initiate eplerenone 25 mg daily, titrate to max 25 mg twice daily. Risk D: Consider therapy modificationErdafitinib: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Erdafitinib.Management: Avoid concomitant use of erdafitinib and moderate CYP2C9 inhibitors when possible. If combined, monitor closely for erdafitinib adverse reactions and consider dose modifications accordingly. Risk D: Consider therapy modificationErgot Derivatives (Vasoconstrictive CYP3A4 Substrates): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates).Risk C: Monitor therapyErlotinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Erlotinib.Risk C: Monitor therapyErythromycin (Systemic): Fluconazole may enhance the QTc-prolonging effect of Erythromycin (Systemic). Fluconazole may increase the serum concentration of Erythromycin (Systemic).Risk X: Avoid combinationEscitalopram: May enhance the QTc-prolonging effect of Fluconazole. Fluconazole may increase the serum concentration of Escitalopram. Risk C: Monitor therapyEszopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eszopiclone.Risk C: Monitor therapyEtizolam: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Etizolam.Risk C: Monitor therapyEtravirine: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Etravirine.Risk C: Monitor therapyEverolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus.Risk C: Monitor therapyFedratinib: Fluconazole may increase the serum concentration of Fedratinib.Risk X: Avoid combinationFelodipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Felodipine.Risk C: Monitor therapyFentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL.Management: Consider fentanyl dose reductions when combined with a moderate CYP3A4 inhibitor. Monitor for respiratory depression and sedation. Upon discontinuation of a CYP3A4 inhibitor, consider a fentanyl dose increase; monitor for signs and symptoms of withdrawal. Risk D: Consider therapy modificationFexinidazole: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Fexinidazole. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may decrease serum concentrations of the active metabolite(s) of Fexinidazole.Management: Consider alternatives to this combination. If combined, monitor for QT interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QT prolongation may be at even higher risk. Also monitor for reduced fexinidazole efficacy. Risk D: Consider therapy modificationFinerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Finerenone.Risk C: Monitor therapyFlibanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Flibanserin.Management: Use of flibanserin with moderate CYP3A4 inhibitors is contraindicated. If starting flibanserin, start 2 weeks after the last dose of the CYP3A4 inhibitor. If starting a CYP3A4 inhibitor, start 2 days after the last dose of flibanserin. Risk X: Avoid combinationFluorouracil Products: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Fluorouracil Products.Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyFlurbiprofen (Systemic): CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Flurbiprofen (Systemic).Risk C: Monitor therapyFluticasone (Nasal): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fluticasone (Nasal).Risk C: Monitor therapyFluticasone (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fluticasone (Oral Inhalation).Risk C: Monitor therapyFluvastatin: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Fluvastatin.Management: Fluvastatin should be used at the lowest effective dose and should not exceed 20 mg twice daily when combined with moderate CYP2C9 inhibitors. Monitor patients closely for increased fluvastatin toxicities when combined. Risk D: Consider therapy modificationFosamprenavir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fosamprenavir.Risk C: Monitor therapyFosaprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fosaprepitant.Risk X: Avoid combinationFosphenytoin-Phenytoin: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Fosphenytoin-Phenytoin.Risk C: Monitor therapyGlasdegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Glasdegib.Risk C: Monitor therapyGuanFACINE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of GuanFACINE.Management: Reduce the extended-release guanfacine dose 50% when combined with a moderate CYP3A4 inhibitor. Monitor for increased guanfacine toxicities when these agents are combined. Risk D: Consider therapy modificationHaloperidol: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol.Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyHYDROcodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of HYDROcodone.Risk C: Monitor therapyIbrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ibrutinib.Management: When treating B-cell malignancies, decrease ibrutinib to 280 mg daily when combined with moderate CYP3A4 inhibitors. When treating graft versus host disease, monitor patients closely and reduce the ibrutinib dose as needed based on adverse reactions. Risk D: Consider therapy modificationIbuprofen: Fluconazole may increase the serum concentration of Ibuprofen.Risk C: Monitor therapyIfosfamide: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide.Risk C: Monitor therapyIloperidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Iloperidone.Risk C: Monitor therapyInfigratinib: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Infigratinib.Risk X: Avoid combinationIrinotecan Products: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, the serum concentration of SN-38 may be increased. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Irinotecan Products.Risk C: Monitor therapyIsavuconazonium Sulfate: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Moderate) may increase isavuconazole serum concentrations.Risk C: Monitor therapyIsradipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Isradipine.Risk C: Monitor therapyItraconazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Itraconazole.Risk C: Monitor therapyIvabradine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivabradine.Risk X: Avoid combinationIvacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor.Management: Ivacaftor dose reductions may be required; consult full drug interaction monograph content for age- and weight-specific dosage recommendations. Risk D: Consider therapy modificationIvosidenib: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Ivosidenib. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modificationIxabepilone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ixabepilone.Risk C: Monitor therapyLansoprazole: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Lansoprazole.Risk C: Monitor therapyLapatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lapatinib.Risk C: Monitor therapyLarotrectinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Larotrectinib.Risk C: Monitor therapyLefamulin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lefamulin.Management: Monitor for lefamulin adverse effects during coadministration of lefamulin tablets with moderate CYP3A4 inhibitors. Risk C: Monitor therapyLemborexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lemborexant.Risk X: Avoid combinationLercanidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lercanidipine.Risk C: Monitor therapyLesinurad: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Lesinurad.Risk C: Monitor therapyLevamlodipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levamlodipine.Risk C: Monitor therapyLevoketoconazole: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Levoketoconazole. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Levoketoconazole.Risk X: Avoid combinationLevoketoconazole: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Levoketoconazole.Risk X: Avoid combinationLevomethadone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levomethadone.Risk C: Monitor therapyLevomilnacipran: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levomilnacipran.Risk C: Monitor therapyLidocaine (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Lidocaine (Systemic). Specifically, concentrations of monoethylglycinexylidide (MEGX) may be increased. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lidocaine (Systemic).Risk C: Monitor therapyLomitapide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide.Risk X: Avoid combinationLonafarnib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lonafarnib.Risk X: Avoid combinationLopinavir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lopinavir.Risk C: Monitor therapyLorlatinib: Fluconazole may increase the serum concentration of Lorlatinib.Management: Avoid use of lorlatinib with fluconazole whenever possible. If the combination cannot be avoided, reduce the lorlatinib dose from 100 mg once daily to 75 mg once daily. Risk D: Consider therapy modificationLornoxicam: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Lornoxicam.Risk C: Monitor therapyLosartan: CYP2C9 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Losartan. CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Losartan.Risk C: Monitor therapyLovastatin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lovastatin.Risk C: Monitor therapyLumateperone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lumateperone.Management: Limit the lumateperone dose to 21 mg once daily when used with a moderate CYP3A4 inhibitor. Risk D: Consider therapy modificationLurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone.Management: US labeling recommends reducing lurasidone dose by 50% with a moderate CYP3A4 inhibitor and initiating 20 mg/day, max 80 mg/day. Some non-US labels recommend initiating lurasidone 20 mg/day, max 40 mg/day. Avoid concurrent use of grapefruit products. Risk D: Consider therapy modificationLurbinectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurbinectedin.Management: Avoid concomitant use of lurbinectedin and moderate CYP3A4 inhibitors when possible. If combined, consider a lurbinectedin dose reduction as clinically indicated. Risk D: Consider therapy modificationMacitentan: Fluconazole may increase the serum concentration of Macitentan.Risk X: Avoid combinationManidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Manidipine.Risk C: Monitor therapyMaraviroc: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Maraviroc.Risk C: Monitor therapyMavacamten: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Mavacamten.Risk X: Avoid combinationMeloxicam: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Meloxicam.Risk C: Monitor therapyMeperidine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Meperidine.Risk C: Monitor therapyMethadone: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Methadone. Management: Consider alternatives to this drug combination. If combined, monitor for increased methadone toxicities (eg, respiratory depression, QTc interval prolongation). Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modificationMethylPREDNISolone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of MethylPREDNISolone.Risk C: Monitor therapyMethysergide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Methysergide.Risk X: Avoid combinationMidazolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Midazolam.Management: Avoid concomitant use of nasal midazolam and moderate CYP3A4 inhibitors. Consider alternatives to use with oral midazolam whenever possible and consider using lower midazolam doses. Monitor patients for sedation and respiratory depression if combined. Risk D: Consider therapy modificationMiFEPRIStone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of MiFEPRIStone.Risk C: Monitor therapyMirodenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mirodenafil.Risk C: Monitor therapyMitapivat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mitapivat.Management: When coadministered with moderate CYP3A4 inhibitors, doses of mitapivat should not exceed 20 mg twice daily. Additionally, patients should be monitored for changes in hemoglobin response and increased mitapivat adverse effects. Risk D: Consider therapy modificationMizolastine: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Mizolastine.Risk X: Avoid combinationMobocertinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Mobocertinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentrations of the active metabolite(s) of Mobocertinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Mobocertinib.Management: Avoid use of QT prolonging moderate CYP3A4 inhibitors with mobocertinib when possible. If combined, the mobocertinib dose should be reduced by approximately 50% (ie, from 160 mg to 80 mg, 120 mg to 40 mg, or 80 mg to 40 mg). Monitor QTc interval closely. Risk D: Consider therapy modificationMoclobemide: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Moclobemide.Risk C: Monitor therapyNaldemedine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naldemedine.Risk C: Monitor therapyNalfurafine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nalfurafine.Risk C: Monitor therapyNaloxegol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol.Management: The use of naloxegol and moderate CYP3A4 inhibitors should be avoided. If concurrent use is unavoidable, reduce naloxegol dose to 12.5 mg once daily and monitor for signs of opiate withdrawal (eg, hyperhidrosis, chills, diarrhea, anxiety, irritability). Risk D: Consider therapy modificationNateglinide: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Nateglinide.Risk C: Monitor therapyNelfinavir: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Nelfinavir.Risk C: Monitor therapyNeratinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Neratinib.Risk C: Monitor therapyNevirapine: Fluconazole may increase the serum concentration of Nevirapine.Risk C: Monitor therapyNIFEdipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NIFEdipine.Risk C: Monitor therapyNiMODipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NiMODipine.Risk C: Monitor therapyNisoldipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nisoldipine.Risk X: Avoid combinationNitrendipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nitrendipine.Risk C: Monitor therapyOlaparib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olaparib.Management: Avoid use of moderate CYP3A4 inhibitors with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib tablets should be reduced to 150 mg twice daily and the dose of olaparib capsules should be reduced to 200 mg twice daily. Risk D: Consider therapy modificationOliceridine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Oliceridine.Risk C: Monitor therapyOlmutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olmutinib.Risk C: Monitor therapyOmeprazole: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Omeprazole.Risk C: Monitor therapyOndansetron: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyOrelabrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Orelabrutinib.Risk X: Avoid combinationOspemifene: Fluconazole may increase the serum concentration of Ospemifene.Risk X: Avoid combinationOxyCODONE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased.Risk C: Monitor therapyPAcl*taxel (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of PAcl*taxel (Conventional).Risk C: Monitor therapyPAcl*taxel (Protein Bound): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of PAcl*taxel (Protein Bound).Risk C: Monitor therapyPacritinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pacritinib.Risk X: Avoid combinationPalbociclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Palbociclib.Risk C: Monitor therapyPalovarotene: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Palovarotene.Risk C: Monitor therapyPanobinostat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Panobinostat.Risk C: Monitor therapyParecoxib: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Parecoxib. Specifically, serum concentrations of the active moiety valdecoxib may be increased.Management: Use the lowest effective dose of parecoxib and consider a dose reduction in patients taking moderate CYP2C9 inhibitors. Risk D: Consider therapy modificationPAZOPanib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of PAZOPanib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of PAZOPanib.Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyPemigatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pemigatinib.Management: If combined use cannot be avoided, reduce the pemigatinib dose from 13.5 mg daily to 9 mg daily, or from 9 mg daily to 4.5 mg daily. Resume prior pemigatinib dose after stopping the moderate inhibitor once 3 half-lives of the inhibitor has passed. Risk D: Consider therapy modificationPentamidine (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyPexidartinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pexidartinib.Management: Avoid use of pexidartinib with moderate CYP3A4 inhibitors if possible. If combined, the pexidartinib dose should be reduced. Decrease 800 mg or 600 mg daily doses to 200 mg twice daily. Decrease doses of 400 mg per day to 200 mg once daily. Risk D: Consider therapy modificationPimavanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimavanserin.Risk C: Monitor therapyPimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus.Risk C: Monitor therapyPimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combinationPONATinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of PONATinib.Risk C: Monitor therapyPrazepam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Prazepam.Risk C: Monitor therapyPraziquantel: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Praziquantel.Risk C: Monitor therapyProguanil: CYP2C19 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Proguanil. CYP2C19 Inhibitors (Strong) may increase the serum concentration of Proguanil.Risk C: Monitor therapyQT-prolonging Antidepressants (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Risk C: Monitor therapyQT-prolonging Antipsychotics (Moderate Risk): QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk).Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyQT-prolonging Class IA Antiarrhythmics (Highest Risk): Fluconazole may enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk).Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modificationQT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyQT-prolonging Class III Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Class III Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modificationQT-Prolonging Inhalational Anesthetics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyQT-prolonging Kinase Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Kinase Inhibitors (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modificationQT-prolonging Kinase Inhibitors (Moderate Risk): QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Kinase Inhibitors (Moderate Risk).Risk C: Monitor therapyQT-prolonging Miscellaneous Agents (Highest Risk): Fluconazole may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Fluconazole.Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modificationQT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Moderate Risk).Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyQT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): Fluconazole may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk).Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyQT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyQT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of Fluconazole. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modificationQT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): Fluconazole may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk).Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyQUEtiapine: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QUEtiapine. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QUEtiapine.Management: Monitor for increased quetiapine toxicities including QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyQuiNIDine: Fluconazole may enhance the QTc-prolonging effect of QuiNIDine. Fluconazole may increase the serum concentration of QuiNIDine.Risk X: Avoid combinationQuinidine (Non-Therapeutic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Quinidine (Non-Therapeutic).Risk C: Monitor therapyRamelteon: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Ramelteon.Risk C: Monitor therapyRanolazine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ranolazine.Management: Limit the ranolazine dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors. Monitor for increased ranolazine effects and toxicities during concomitant use. Risk D: Consider therapy modificationRed Yeast Rice: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Red Yeast Rice.Risk C: Monitor therapyRegorafenib: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Regorafenib.Risk C: Monitor therapyRifabutin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rifabutin.Risk C: Monitor therapyRifAMPin: May decrease the serum concentration of Fluconazole. Fluconazole may increase the serum concentration of RifAMPin. Management: Consider increasing the dose of fluconazole when used concurrently with rifampin. When combined, monitor for both reduced clinical efficacy of fluconazole and increased rifampin toxicities. Risk D: Consider therapy modificationRifapentine: May decrease the serum concentration of Fluconazole. Risk C: Monitor therapyRimegepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rimegepant.Management: If taking rimegepant for the acute treatment of migraine, avoid a second dose of rimegepant within 48 hours when used concomitantly with moderate CYP3A4 inhibitors. No dose adjustment needed if using rimegepant for prevention of episodic migraine. Risk D: Consider therapy modificationRisperiDONE: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of RisperiDONE.Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapyRitonavir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ritonavir.Risk C: Monitor therapyRivaroxaban: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rivaroxaban. This warning is more specifically for drugs that are inhibitors of both CYP3A4 and P-glycoprotein.For erythromycin, refer to more specific erythromycin-rivaroxaban monograph recommendations.Risk C: Monitor therapyRoflumilast-Containing Products: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Roflumilast-Containing Products.Risk C: Monitor therapyRupatadine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rupatadine.Risk C: Monitor therapyRuxolitinib (Systemic): Fluconazole may increase the serum concentration of Ruxolitinib (Systemic).Management: Avoid fluconazole doses over 200 mg/day in combination with ruxolitinib. Dose adjustments are required in some circ*mstances. See full interaction monograph for details. Risk D: Consider therapy modificationSaccharomyces boulardii: Antifungal Agents (Systemic, Oral) may diminish the therapeutic effect of Saccharomyces boulardii.Risk X: Avoid combinationSalmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol.Risk C: Monitor therapySAXagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SAXagliptin.Risk C: Monitor therapySelpercatinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Selpercatinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Selpercatinib.Management: Avoid combination if possible. If use is necessary, reduce selpercatinib dose as follows: from 120mg twice/day to 80mg twice/day, or from 160mg twice/day to 120mg twice/day. Monitor QT interval more closely for QTc interval prolongation and arrhythmias. Risk D: Consider therapy modificationSelumetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Selumetinib.Management: Avoid concomitant use when possible. If combined, selumetinib dose reductions are recommended and vary based on body surface area and selumetinib dose. For details, see the full drug interaction monograph or selumetinib prescribing information. Risk D: Consider therapy modificationSertindole: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Sertindole. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Sertindole.Risk X: Avoid combinationSildenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sildenafil.Risk C: Monitor therapySilodosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Silodosin.Risk C: Monitor therapySimeprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.Risk X: Avoid combinationSimvastatin: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simvastatin.Risk C: Monitor therapySiponimod: Fluconazole may increase the serum concentration of Siponimod.Risk X: Avoid combinationSirolimus (Conventional): Fluconazole may increase the serum concentration of Sirolimus (Conventional).Management: Monitor for increased serum concentrations of sirolimus if combined with fluconazole. Lower initial sirolimus doses or sirolimus dose reductions will likely be required. Risk D: Consider therapy modificationSirolimus (Protein Bound): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sirolimus (Protein Bound).Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a moderate CYP3A4 inhibitor. Risk D: Consider therapy modificationSolifenacin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Solifenacin.Risk C: Monitor therapySonidegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sonidegib.Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible.When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions). Risk D: Consider therapy modificationSulfonylureas: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Sulfonylureas.Risk C: Monitor therapySUNItinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of SUNItinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of SUNItinib.Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapySuvorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Suvorexant.Management: The recommended dose of suvorexant is 5 mg daily in patients receiving a moderate CYP3A4 inhibitor. The dose can be increased to 10 mg daily (maximum dose) if necessary for efficacy. Risk D: Consider therapy modificationTacrolimus (Systemic): Fluconazole may increase the serum concentration of Tacrolimus (Systemic).Management: Monitor tacrolimus concentrations closely and adjust oral tacrolimus dose as necessary when concomitantly administered with fluconazole. Reduced doses of tacrolimus will likely be required. Risk D: Consider therapy modificationTadalafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tadalafil.Risk C: Monitor therapyTamsulosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin.Risk C: Monitor therapyTazemetostat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tazemetostat.Management: Avoid when possible. If combined, reduce tazemetostat dose from 800 mg twice daily to 400 mg twice daily, from 600 mg twice daily to 400 mg in AM and 200 mg in PM, or from 400 mg twice daily to 200 mg twice daily. Risk D: Consider therapy modificationTelithromycin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Telithromycin.Risk C: Monitor therapyTemsirolimus: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be increased.Risk C: Monitor therapyTerfenadine: Fluconazole may enhance the QTc-prolonging effect of Terfenadine. Fluconazole may increase the serum concentration of Terfenadine.Management: Concomitant use of fluconazole at doses of 400 mg/day or greater and terfenadine is contraindicated and should be avoided. If lower doses of fluconazole and terfenadine are combined, monitor patients for QT-prolongation. Risk D: Consider therapy modificationTetrahydrocannabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol.Risk C: Monitor therapyTetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol.Risk C: Monitor therapyTetrahydrocannabinol and Cannabidiol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. Specifically, concentrations of tetrahydrocannabinol may be increased.Risk C: Monitor therapyTetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol.Risk C: Monitor therapyTezacaftor and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tezacaftor and Ivacaftor.Management: If combined with moderate CYP3A4 inhibitors, give tezacaftor/ivacaftor in the morning, every other day; give ivacaftor in the morning, every other day on alternate days. Tezacaftor/ivacaftor dose depends on age and weight; see full Lexi-Interact monograph Risk D: Consider therapy modificationTheophylline Derivatives: Fluconazole may increase the serum concentration of Theophylline Derivatives.Risk C: Monitor therapyThiotepa: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Thiotepa.Risk C: Monitor therapyTicagrelor: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ticagrelor.Risk C: Monitor therapyTipranavir: Fluconazole may increase the serum concentration of Tipranavir.Management: Limit fluconazole adult maximum dose to 200 mg/day in patients treated with tipranavir. Risk D: Consider therapy modificationTofacitinib: Fluconazole may increase the serum concentration of Tofacitinib.Management: Tofacitinib dose reductions are recommended when combined with fluconazole. Recommended dose adjustments vary by tofacitinib formulation and therapeutic indication. See full Lexi Interact monograph for details. Risk D: Consider therapy modificationTolterodine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolterodine.Risk C: Monitor therapyTolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan.Management: Avoid this combination with Samsca brand of tolvaptan. Reduce dose for Jynarque brand: 90 mg AM and 30 mg PM, reduce to 45 mg AM and 15 mg PM; 60 mg AM and 30 mg PM, reduce to 30 mg AM and 15 mg PM; 45 mg AM and 15 mg PM, reduce to 15 mg AM and PM. Risk D: Consider therapy modificationTorsemide: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Torsemide.Risk C: Monitor therapyTrabectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin.Risk C: Monitor therapyTraMADol: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of TraMADol. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of TraMADol.Risk C: Monitor therapyTraZODone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of TraZODone.Risk C: Monitor therapyTretinoin (Systemic): Fluconazole may increase the serum concentration of Tretinoin (Systemic).Risk C: Monitor therapyTriazolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Triazolam.Management: Consider triazolam dose reduction in patients receiving concomitant moderate CYP3A4 inhibitors. Risk D: Consider therapy modificationUbrogepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ubrogepant.Management: Use an initial ubrogepant dose of 50 mg and avoid a second dose for 24 hours when used with moderate CYP3A4 inhibitors. Risk D: Consider therapy modificationUdenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Udenafil.Risk C: Monitor therapyUlipristal: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ulipristal.Risk C: Monitor therapyValbenazine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Valbenazine.Risk C: Monitor therapyVardenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vardenafil.Management: Limit Levitra (vardenafil) dose to a single 5 mg dose within a 24-hour period if combined with moderate CYP3A4 inhibitors. Avoid concomitant use of Staxyn (vardenafil) and moderate CYP3A4 inhibitors. Combined use is contraindicated outside of the US. Risk D: Consider therapy modificationVenetoclax: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Venetoclax.Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with moderate CYP3A4 inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of moderate CYP3A4 inhibitors. Risk D: Consider therapy modificationVerapamil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Verapamil.Risk C: Monitor therapyVilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone.Risk C: Monitor therapyVinBLAStine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of VinBLAStine.Risk C: Monitor therapyVinCRIStine: Fluconazole may increase the serum concentration of VinCRIStine.Risk C: Monitor therapyVinCRIStine (Liposomal): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of VinCRIStine (Liposomal).Risk C: Monitor therapyVindesine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vindesine.Risk C: Monitor therapyVinflunine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Vinflunine. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vinflunine.Risk C: Monitor therapyVitamin K Antagonists (eg, warfarin): Fluconazole may increase the serum concentration of Vitamin K Antagonists.Management: Consider alternatives when possible. If combined, consider reducing the vitamin K antagonist dose by 10% to 20% if combined with fluconazole. Monitor for increased anticoagulant effects (ie, increased INR, bleeding) to guide further dose adjustments. Risk D: Consider therapy modificationVoclosporin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Voclosporin.Management: Decrease the voclosporin dose to 15.8 mg in the morning and 7.9 mg in the evening when combined with moderate CYP3A4 inhibitors. Risk D: Consider therapy modificationVorapaxar: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vorapaxar.Risk C: Monitor therapyVoriconazole: Fluconazole may enhance the QTc-prolonging effect of Voriconazole. Fluconazole may increase the serum concentration of Voriconazole.Risk X: Avoid combinationZanubrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zanubrutinib.Management: Decrease the zanubrutinib dose to 80 mg twice daily during coadministration with a moderate CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details. Risk D: Consider therapy modificationZopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zopiclone.Risk C: Monitor therapyReproductive ConsiderationsBased on human data, in utero exposure to high doses of fluconazole may cause fetal harm. According to the manufacturer, patients who may become pregnant and who are taking higher doses (≥400 mg/day) should use effective contraception during therapy and for ~1 week after the final fluconazole dose.Pregnancy ConsiderationsBased on human data, in utero exposure to high doses of fluconazole may cause fetal harm. Following exposure during the first trimester, malformations have been noted in humans when maternal fluconazole was used in higher doses (≥400 mg/day). Abnormalities reported include brachycephaly, abnormal facies, abnormal calvarial development, cleft palate, femoral bowing, thin ribs and long bones, arthrogryposis, and congenital heart disease. Fetal outcomes following exposure to lower doses is less clear and additional study is needed to confirm an association between maternal use of low dose fluconazole and an increased risk of birth defects. However, epidemiological studies of fluconazole ≤150 mg as a single dose or repeated doses in the first trimester suggest a potential risk of spontaneous abortion and malformations (Budani 2021; Diflucan [fluconazole oral] prescribing information).Oral fluconazole for the treatment of vagin*l candidiasis is not recommended during pregnancy. Topical therapy for oral or vagin*l candidiasis is recommended in pregnant patients (HHS [OI adult 2020]; Workowski [CDC 2021]). Secondary prophylaxis or chronic maintenance therapy using oral or IV fluconazole should not be initiated during pregnancy for esophageal, oropharyngeal, or vagin*l candidiasis; fluconazole should be discontinued if pregnancy occurs during therapy (HHS [OI adult 2020]). Fluconazole is not the treatment of choice for invasive candidiasis in pregnant patients (IDSA [Pappas 2016]). Fluconazole may be used for the treatment of cryptococcosis or coccidioidomycosis after the first trimester if otherwise appropriate (HHS [OI adult 2020]; IDSA [Galgiani 2016]; Pastick 2020).Monitoring ParametersPeriodic liver function (AST, ALT, alkaline phosphatase), renal function tests, serum potassium, CBC with differential and platelet count; conjugated bilirubin in neonates (Egunsola 2013)Mechanism of ActionInterferes with fungal cytochrome P450 activity (lanosterol 14-α-demethylase), decreasing ergosterol synthesis (principal sterol in fungal cell membrane) and inhibiting cell membrane formationPharmaco*kinetics (Adult data unless noted)Absorption: Oral: Well absorbed; food does not affect extent of absorptionDistribution: Vd: ~0.6 L/kg; widely throughout body with good penetration into CSF, eye, peritoneal fluid, sputum, skin, and urineRelative diffusion blood into CSF: Adequate with or without inflammation (exceeds usual MICs)CSF:blood level ratio: Normal meninges: 50% to 90%; Inflamed meninges: ~80%Protein binding, plasma: 11% to 12%Bioavailability: Oral: >90%Half-life elimination: Normal renal function: ~30 hours (range: 20 to 50 hours); Elderly: 46.2 hours; Neonates (gestational age 26 to 29 weeks): 73.6 to 46.6 hours (decreases with increasing postnatal age); Pediatric patients 9 months to 15 years: 19.5 to 25 hoursTime to peak, serum: Oral: 1 to 2 hours Excretion: Urine (80% as unchanged drug)Pharmaco*kinetics: Additional ConsiderationsAltered kidney function: Pharmaco*kinetics are markedly affected; there is an inverse relationship between half-life and creatinine clearance.Additional InformationDosing equivalency suggested by the manufacturer's labeling: Pediatric patients 3 mg/kg = Adults 100 mg Pediatric patients 6 mg/kg = Adults 200 mg Pediatric patients 12 mg/kg = Adults 400 mg Pricing: USSolution (Fluconazole in Sodium Chloride Intravenous)100 mg/50 mL 0.9% (per mL): $0.12200 mg/100 mL 0.9% (per mL): $0.05 - $0.58400 mg/200 mL 0.9% (per mL): $0.03 - $0.42Suspension (reconstituted) (Diflucan Oral)10 mg/mL (per mL): $0.5840 mg/mL (per mL): $0.96Suspension (reconstituted) (Fluconazole Oral)10 mg/mL (per mL): $0.99 - $1.0340 mg/mL (per mL): $3.59 - $3.73Tablets (Diflucan Oral)50 mg (per each): $1.36100 mg (per each): $1.36150 mg (per each): $73.05200 mg (per each): $75.11Tablets (Fluconazole Oral)50 mg (per each): $0.49 - $5.60100 mg (per each): $8.75 - $8.80150 mg (per each): $1.29 - $14.01200 mg (per each): $14.32 - $14.40Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalAfungil (CR, DO, GT, HN, MX, NI, PA, SV);Apicon (BD);Asperlican (VN);Avezol (MY);Baten (DO, EC, GT, HN, PA, SV);Beagyne (FR);Biozole (MY);Burnax (EC);Canazole (BD);Candid (BD);Candifix (ES);Candinil (LK);Candivast (BH);Canesoral (AU);Canesten Oral (GB);Cryptal (ID);Damicol (AR);Diflazole (IE);Diflazon (UA, VN);Diflucan (AT, AU, BB, BE, BF, BG, BH, BJ, BM, BS, BZ, CH, CI, CL, CN, CR, CZ, DE, DK, DO, EE, EG, ES, ET, FI, GB, GH, GM, GN, GT, GY, HK, HN, HR, HU, ID, IE, IS, IT, JM, JO, JP, KE, KR, KW, LB, LR, LT, LU, LV, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NI, NL, NO, NZ, PA, PE, PH, PL, PT, QA, RO, RU, SA, SC, SD, SE, SI, SK, SL, SN, SR, SV, TH, TN, TR, TT, TW, TZ, UG, VE, ZA, ZM);Difluvid (MY, PH);Difluzol (UA);Difluzole (KR);Difnazol (KR);Dimycon (HR);Dizole (AU);Dofil (CR, DO, GT, HN, NI, PA, SV);Duflucan (UA);Dyzolor (PH);Eapacon (ET);Exomax (BH, HK, ZA);FCZ Infusion (ID);Flocan (KR);FLU-D (TW);Flucan (TR);Flucand (BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE);Flucanol (IL, ZW);Flucazol (AE, BR, CH, CY, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE);Flucazole (NZ);Flucogus (TW);Flucol (IE);Flucon (KR, MY);Flucona (KR);Flucona-Denk (TZ);Fluconal (BD);Fluconaz (PH);Flucoral (BH, ID);Flucoran (NZ);Flucoxan (MX);Flucozal (BR, LK, MT, PK);Flucozol (MY);Fludicon (HK);Fludizol (TH);Fluken (ZW);Flumax (KR);Flumyc (ZW);Flunazol (CY);Flunazole (TW);Flunco (TH);Fluxar (ID);Fluzin (KR);Fluzole (AU, LK);Fluzoral (TH);Forcan (CZ, IN, LV, VN);f*ckole (MY, PH);Fumay (TW);Funa (TH);Funazol (KR);Funex (CO);Fungata (DE);Fungicon (ZW);Fungostatin (GR);Fungoz (ID);Funzela (PH);Funzol (JO, LB, QA, SA);Fuzolan (ID);Fuzolsel (VN);Glonaz (PH);Insep (ZA);Jenfunga (EG);Klevaflu (VN);Kyrin (TH);Medoflucon (CN, SG);Mutum (AR, PE);Mycocyst (BM, BS, BZ, GY, JM, SR, TT, UA);Mycomox (LV);Mycorest (SG);Mycosyst (HU);Mycozole (PH);Neoconal (KR);Nobzol-1 (CO);Nobzol-2 (CO);Odaft (MY, PH);Omastin (SG);Onecan (LK);Oneflu (KR);Oramax (AE, ET, KW, LB, QA, SA);Oxifungol (MX);Oxole (AU);Reforce (PT);Sixanol (PY, UY);Solona (SE);Spirolac (PY);Stabilanol (ET, IL);Stalene (TH);Syscan (ET, IN);Tavor (EC);Tinazole (KR);Treflucan (AE, CY, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE);Triconal (EG);Triflucan (FR, IL, TR);Trigal (BD);Uzol (TW);Zemyc (ID);Zocol (MY);Zoldicam (MX);Zoleshot (PH);Zolmed (VN)For country code abbreviations (show table)<800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 40-NF 35). Rockville, MD: United States Pharmacopeia Convention; 2017:83-102.Adler NR, Lin MJ, Cameron R, Gin D. Fluconazole-induced Sweet's syndrome: A novel association. Australas J Dermatol. 2018;59(2):e160-e161. doi:10.1111/ajd.12709 [PubMed 28891066]Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319. [PubMed 11487763]Aleck KA, Bartley DL. Multiple malformation syndrome following fluconazole use in pregnancy: report of an additional patient. Am J Med Genet. 1997;72(3):253-256. [PubMed 9332650]Alobaid AS, Wallis SC, Jarrett P, et al. Effect of obesity on the population pharmaco*kinetics of fluconazole in critically ill patients. Antimicrob Agents Chemother. 2016;60(11):6550-6557. doi:10.1128/AAC.01088-16 [PubMed 27550344]Alsadhan A, Taher M, Krol A. Acute generalized exanthematous pustulosis induced by oral fluconazole. J Cutan Med Surg. 2002;6(2):122-124. doi:10.1007/s10227-001-0035-8 [PubMed 11992184]Ameen M, Lear JT, Madan V, Mohd Mustapa MF, Richardson M. British Association of Dermatologists' guidelines for the management of onychomycosis 2014. Br J Dermatol. 2014;171(5):937-958. doi:10.1111/bjd.13358 [PubMed 25409999]American Academy of Pediatrics (AAP). In: Kimberlin DW, Brady MT, Jackson MA, Long SA, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. American Academy of Pediatrics; 2018.American Academy of Pediatrics Committee on Drugs. "Inactive" ingredients in pharmaceutical products: update (subject review). Pediatrics. 1997;99(2):268-278. [PubMed 9024461]Ampel NM. Coccidioidomycosis in compromised hosts. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 21, 2020.Anaissie EJ, Kontoyiannis DP, Huls C, et al. Safety, plasma concentrations, and efficacy of high-dose fluconazole in invasive mold infections. J Infect Dis. 1995;172(2):599-602. doi:10.1093/infdis/172.2.599 [PubMed 7622915]Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016;100(1):42-52. doi:10.1002/cpt.377 [PubMed 27060684]Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th ed. American College of Physicians; 2007.Ashbee HR, Barnes RA, Johnson EM, Richardson MD, Gorton R, Hope WW. Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology. J Antimicrob Chemother. 2014;69(5):1162-1176. doi:10.1093/jac/dkt508 [PubMed 24379304]Aslam S, Rotstein C; AST Infectious Disease Community of Practice. Candida infections in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13623. doi:10.1111/ctr.13623 [PubMed 31155770]Baddley JW, Forrest GN; AST Infectious Diseases Community of Practice. Cryptococcosis in solid organ transplantation-guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13543. doi:10.1111/ctr.13543 [PubMed 30900315]Based on expert opinion.Bavbek S, Yilmaz İ, Sözener ZÇ. Fixed drug eruption caused by ornidazole and fluconazole but not isoconazole, itraconazole, ketoconazole and metronidazole. J Dermatol. 2013;40(2):134-135. doi:10.1111/1346-8138.12023 [PubMed 23110686]Benitez LL, Carver PL. Adverse effects associated with long-term administration of azole antifungal agents. Drugs. 2019;79(8):833-853. doi:10.1007/s40265-019-01127-8 [PubMed 31093949]Benjamin Lash D, Jolliff J, Munoz A, Heidari A. Cross-reactivity between voriconazole, fluconazole and itraconazole. J Clin Pharm Ther. 2016;41(5):566-567. doi:10.1111/jcpt.12417 [PubMed 27430151]Berens P, Eglash A, Malloy M, Steube AM. ABM clinical protocol #26: persistent pain with breastfeeding. Breastfeed Med. 2016;11(2):46-53. doi:10.1089/bfm.2016.29002.pjb [PubMed 26881962]Bergner R, Hoffmann M, Riedel KD, et al. Fluconazole dosing in continuous veno-venous haemofiltration (CVVHF): need for a high daily dose of 800 mg. Nephrol Dial Transplant. 2006;21(4):1019-1023. [PubMed 16311263]Berl T, Wilner KD, Gardner M, et al. Pharmaco*kinetics of fluconazole in renal failure. J Am Soc Nephrol. 1995;6(2):242-247. [PubMed 7579091]Blair JE, Ampel NM. Coccidioidal meningitis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 24, 2020.Bodley V, Powers D. Long-term treatment of a breastfeeding mother with fluconazole-resolved nipple pain caused by yeast: a case study. J Hum Lact.1997;13(4):307-311. doi:10.1177/089033449701300416 [PubMed 9429366]Bradley JS, Nelson JD, Barnett ED, et al, eds. Nelson's Pediatric Microbial Therapy. 27th ed. American Academy of Pediatrics; 2021.Bradsher RW. Treatment of blastomycosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 21, 2020.Brammer KW, Farrow PR, Faulkner JK. Pharmaco*kinetics and tissue penetration of fluconazole in humans. Rev Infect Dis. 1990;12(suppl 3):S318-S326. doi:10.1093/clinids/12.supplement_3.s318 [PubMed 2184510]Bratzler DW, Dellinger EP, Olsen KM, et al; American Society of Health-System Pharmacists; Infectious Diseases Society of America; Surgical Infection Society; Society for Healthcare Epidemiology of America. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013;70(3):195-283. doi: 10.2146/ajhp120568. [PubMed 23327981]Brent NB. Thrush in the breastfeeding dyad: results of a survey on diagnosis and treatment. Clin Pediatr (Phila). 2001;40(9):503-506. doi: 10.1177/000992280104000905. [PubMed 11583049]Brockow K, Przybilla B, Aberer W, et al. Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM). Allergo J Int. 2015;24(3):94-105. doi:10.1007/s40629-015-0052-6 [PubMed 26120552]Brodell RT, Dolohanty LB. Intertrigo. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 23, 2021.Budani MC, Fensore S, Di Marzio M, Tiboni GM. Maternal use of fluconazole and congenital malformations in the progeny: a meta-analysis of the literature. Reprod Toxicol. 2021;100:42-51. doi:10.1016/j.reprotox.2020.12.018 [PubMed 33383164]Burkart JM, Bleyer A. Peritoneal catheter exit-site and tunnel infections in peritoneal dialysis in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 11, 2018.Candidiasis (Mucocutaneous). In: US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/Adult_OI.pdf. Updated May 26, 2020. Accessed June 16, 2021.Centers for Disease Control (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm. [PubMed 6810084]Centers for Disease Control and Prevention (CDC). Guidelines for Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Adults and Adolescents. Recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009;58(RR-4):1-207. [PubMed 19357635]Chakravarty C, Singh PM, Trikha A, Arora MK. Fluconazole-induced recurrent ventricular fibrillation leading to multiple cardiac arrests. Anaesth Intensive Care. 2009;37(3):477-480. doi:10.1177/0310057X0903700311 [PubMed 19499872]Chapman SW, Dismukes WE, Proia LA, et al; Infectious Diseases Society of America. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(12):1801-1812. [PubMed 18462107]Chen CM, Ho MW, Yu WL, Wang JH. Fungal peritonitis in peritoneal dialysis patients: effect of fluconazole treatment and use of the twin-bag disconnect system. J Microbiol Immunol Infect. 2004;37(2):115-120. [PubMed 15181494]Chen SC, Korman TM, Slavin MA, et al; Australia and New Zealand Mycoses Interest Group (ANZMIG) Cryptococcus Study. Antifungal therapy and management of complications of cryptococcosis due to Cryptococcus gattii. Clin Infect Dis. 2013;57(4):543-551. doi: 10.1093/cid/cit341. [PubMed 23697747]Chetwynd EM, Ives TJ, Payne PM, Edens-Bartholomew N. Fluconazole for postpartum candidal mastitis and infant thrush. J Hum Lact. 2002;18(2):168-171. [PubMed 12033079]Cohen LG, DiBiasio A, Lisco SJ, Hurford WE. Fluconazole serum concentrations and pharmaco*kinetics in an obese patient. Pharmacotherapy. 1997;17(5):1023-1026. [PubMed 9324192]Coldiron BM, Manders SM. Persistent Candida intertrigo treated with fluconazole. Arch Dermatol. 1991;127(2):165-166. [PubMed 1990982]Como JA, Dismukes WE. Oral Azole Drugs as Systemic Antifungal Therapy. N Engl J Med. 1993;330(4):263-272.Cousin L, Berre ML, Launay-Vacher V, Izzedine H, Deray G. Dosing guidelines for fluconazole in patients with renal failure. Nephrol Dial Transplant. 2003;18(11):2227-2231. [PubMed 14551347]Cox GM, Perfect JR. Cryptococcus neoformans meningoencephalitis in persons with HIV: Treatment and prevention. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 18, 2022a.Cox GM, Perfect JR. Cryptococcus neoformans: Treatment of meningoencephalitis and disseminated infection in patients without HIV. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 18, 2022b.Cox GM, Perfect JR. Cryptococcus neoformans infection outside the central nervous system. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 21, 2020.Craythorne E, Creamer D. Stevens-Johnson syndrome due to prophylactic fluconazole in two patients with liver failure. Clin Exp Dermatol. 2009;34(7):e389-e390. doi:10.1111/j.1365-2230.2009.03365.x [PubMed 19548943]Davis MR, Nguyen MH, Donnelley MA, Thompson Iii GR. Tolerability of long-term fluconazole therapy. J Antimicrob Chemother. 2019;74(3):768-771. doi:10.1093/jac/dky501 [PubMed 30535104]Demir S, Cetin EA, Unal D, et al. Generalized fixed drug eruption induced by fluconazole without cross-reactivity to itraconazole: lymphocyte transformation test confirms the diagnosis. Drug Saf Case Rep. 2018;5(1):2. doi:10.1007/s40800-017-0067-7 [PubMed 29294202]Di Leo E, Nettis E, Priore MG, Ferrannini A, Vacca A. Maculopapular rash due to fluconazole. Clin Exp Dermatol. 2009;34(3):404. doi:10.1111/j.1365-2230.2008.02895.x [PubMed 18627382]Di Lernia V, Ricci C. Fluconazole-induced acute generalized exanthematous pustulosis. Indian J Dermatol. 2015;60(2):212. doi:10.4103/0019-5154.152572 [PubMed 25814733]Diflucan (fluconazole) [prescribing information]. New York, NY: Roerig, Division of Pfizer Inc; March 2022.Diflucan (fluconazole in Dextrose injection and fluconazole in Sodium Chloride injection) [prescribing information]. New York, NY: Pfizer; March 2022.Douglas P. Overdiagnosis and overtreatment of nipple and breast candidiasis: a review of the relationship between diagnoses of mammary candidiasis and Candida albicans in breastfeeding women. Womens Health (Lond). 2021;17:17455065211031480. doi:10.1177/17455065211031480 [PubMed 34269140]Drake L, Babel D, Stewart DM, et al. Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the fingernail. J Am Acad Dermatol. 1998;38(6, pt 2):S87-S94. doi:10.1016/s0190-9622(98)70491-8 [PubMed 9631990]Driessen M, Ellis JB, Cooper PA, et al. Fluconazole vs. amphotericin B for the treatment of neonatal fungal septicemia: a prospective randomized trial. Pediatr Infect Dis J. 1996;15(12):1107-1112. [PubMed 8970221]Durand ML, Kauffman CA. Treatment of endogenous endophthalmitis due to Candida species. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 24, 2022.Duswald KH, Penk A, Pittrow L. High-dose therapy with fluconazole > or = 800 mg day-1. Mycoses. 1997;40(7-8):267-277. doi:10.1111/j.1439-0507.1997.tb00231.x [PubMed 9476509]Egunsola O, Adefurin A, Fakis A, Jacqz-Aigrain E, Choonara I, Sammons H. Safety of fluconazole in paediatrics: a systematic review. Eur J Clin Pharmacol. 2013;69(6):1211-1221. [PubMed 23325436]Eichenwald EC, ed. Cloherty and Stark's Manual of Neonatal Care. 8th ed. Lippincott Williams & Wilkins; 2017.Fishman JA, Alexander BD. Prophylaxis of infections in solid organ transplantation. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 23, 2020.Fluconazole. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; May 21, 2017. [PubMed 31643623]Fluconazole injection (fluconazole in sodium chloride, IV infusion, USP) [prescribing information]. Deerfield, IL: Baxter Healthcare Corp; May 2018.Fluconazole injection [prescribing information]. Berkeley Heights, NJ: Hikma Pharmaceuticals USA Inc; July 2021.Fluconazole injection [prescribing information]. Eatontown, NJ: West-Ward Pharmaceutical Corp; December 2018.Foo H, Gottlieb T. Lack of cross-hepatotoxicity between voriconazole and posaconazole. Clin Infect Dis. 2007;45(6):803-805. doi:10.1086/521174 [PubMed 17712772]Force RW. Fluconazole concentrations in breast milk. Pediatr Infect Dis J. 1995;14(3):235-236. [PubMed 7761190]Galgiani JN, Ampel NM, Blair JE, et al. 2016 Infectious Diseases Society of America (IDSA) clinical practice guideline for the treatment of coccidioidomycosis. Clin Infect Dis. 2016;63(6):e112-e146. doi:10.1093/cid/ciw360 [PubMed 27470238]Gandhi PJ, Menezes PA, Vu HT, Rivera AL, Ramaswamy K. Fluconazole- and levofloxacin-induced torsades de pointes in an intensive care unit patient. Am J Health Syst Pharm. 2003;60(23):2479-2483. doi:10.1093/ajhp/60.23.2479 [PubMed 14686224]Gayam V, Khalid M, Dahal S, Garlapati P, Gill A. Hyperacute liver injury following intravenous fluconazole: a rare case of dose-independent hepatotoxicity. J Family Med Prim Care. 2018;7(2):451-454. doi:10.4103/jfmpc.jfmpc_330_17 [PubMed 30090793]George J, Sharma A, Dixit R, Chhabra N, Sharma S. Toxic epidermal necrolysis caused by fluconazole in a patient with human immunodeficiency virus infection. J Pharmacol Pharmacother. 2012;3(3):276-278. doi:10.4103/0976-500X.99445 [PubMed 23129968]Georgiadou SP, Tarrand J, Sipsas NV, Kontoyiannia DP. Candiduria in haematologic malignancy patients without a urinary catheter: nothing more than a frailty marker? Mycoses. 2013;56(3):311-314 doi:10.1111/myc.12024 [PubMed 23170870]Gharibian KN, Mueller BA. Fluconazole dosing predictions in critically-ill patients receiving prolonged intermittent renal replacement therapy: a Monte Carlo simulation approach. Clin Nephrol. 2016;86(7):43-50. doi:10.5414/CN108824 [PubMed 27251341]Glasmacher A, Cornely O, Ullmann AJ, et al; Itraconazole Research Group of Germany. An open-label randomized trial comparing itraconazole oral solution with fluconazole oral solution for primary prophylaxis of fungal infections in patients with haematological malignancy and profound neutropenia. J Antimicrob Chemother. 2006;57(2):317-325. [PubMed 16339606]Glickman JD, Cox GM, Kauffman CA. Fungal peritonitis in peritoneal dialysis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 24, 2022.Goldman M, Cloud GA, Wade KD, et al. A randomized study of the use of fluconazole in continuous versus episodic therapy in patients with advanced HIV infection and a history of oropharyngeal candidiasis: AIDS Clinical Trials Group Study 323/Mycoses Study Group Study 40. Clin Infect Dis. 2005;41(10):1473-1480. doi:10.1086/497373 [PubMed 16231260]Goldstein AO, Goldstein BG. Dermatophyte (tinea) infections. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 24, 2022a.Goldstein BG, Goldstein AO. Tinea versicolor (pityriasis versicolor). Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 12, 2022b.Gómez-López A. Antifungal therapeutic drug monitoring: focus on drugs without a clear recommendation. Clin Microbiol Infect. 2020;26(11):1481-1487. doi:10.1016/j.cmi.2020.05.037 [PubMed 32535150]Gould FK, Denning DW, Elliott TS, et al. Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother. 2012;67(2):269-89. doi:10.1093/jac/dkr450 [PubMed 22086858]Gupta AK, Cooper EA. Update in antifungal therapy of dermatophytosis. Mycopathologia. 2008;166(5-6):353-367. doi:10.1007/s11046-008-9109-0 [PubMed 18478357]Healy CM, Baker CJ. Fluconazole Prophylaxis in the Neonatal Intensive Care Unit. Pediatr Infect Dis J. 2009;28(1):49-52. [PubMed 19106754]Heintz BH, Matzke GR, Dager WE. Antimicrobial dosing concepts and recommendations for critically ill adult patients receiving continuous renal replacement therapy or intermittent hemodialysis. Pharmacotherapy. 2009;29(5):562-577. doi:10.1592/phco.29.5.562 [PubMed 19397464]Hoetzenecker W, Nägeli M, Mehra ET, et al. Adverse cutaneous drug eruptions: current understanding. Semin Immunopathol. 2016;38(1):75-86. doi:10.1007/s00281-015-0540-2 [PubMed 26553194]Hope WW, Castagnola E, Groll AH, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: prevention and management of invasive infections in neonates and children caused by Candida spp. Clin Microbiol Infect. 2012;18(suppl 7):38-52. [PubMed 23137136]Hornik CD, Bondi DS, Greene NM, Cober MP, John B. Review of fluconazole treatment and prophylaxis for invasive Candidiasis in neonates. J Pediatr Pharmacol Ther. 2021;26(2):115-122. doi:10.5863/1551-6776-26.2.115 [PubMed 33603574]Islam S, Singer M, Kulhanjian JA. Toxic epidermal necrolysis in a neonate receiving fluconazole. J Perinatol. 2014;34(10):792-794. doi:10.1038/jp.2014.92 [PubMed 25263725]Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126. doi:10.1056/NEJM200007133430208 [PubMed 10891521]Jaroszewski D, Blair JE, Ampel NM. Management of pulmonary sequelae and complications of coccidioidomycosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 7, 2020.Jarvis JN, Lawrence DS, Meya DB, et al; Ambition Study Group. Single-dose liposomal amphotericin B treatment for cryptococcal meningitis. N Engl J Med. 2022;386(12):1109-1120. doi:10.1056/NEJMoa2111904 [PubMed 35320642]Jick SS. Pregnancy outcomes after maternal exposure to fluconazole. Pharmacotherapy. 1999;19(2):221-222. [PubMed 10030772]Joseph M, Brady R, Attridge R, et al. Critically ill recipients of weight-based fluconazole meeting drug-induced liver injury network criteria. Hosp Pharm. 2019;54(6):378-384. doi:10.1177/0018578718802583 [PubMed 31762485]Kao WY, Su CW, Huang YS, et al. Risk of oral antifungal agent-induced liver injury in Taiwanese. Br J Clin Pharmacol. 2014;77(1):180-189. doi:10.1111/bcp.12178 [PubMed 23750489]Karakas M, Durdu M, Memişoğlu HR. Oral fluconazole in the treatment of tinea versicolor. J Dermatol. 2005;32(1):19-21. [PubMed 15841655]Kauffman CA. Esophageal candidiasis in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 23, 2021c.Kauffman CA. Candida infections of the abdomen and thorax. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 24, 2022d.Kauffman CA. Oropharyngeal candidiasis in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 17, 2021e.Khazan M, Mathis AS. Probable case of torsades de pointes induced by fluconazole. Pharmacotherapy. 2002;22(12):1632-1637. doi:10.1592/phco.22.17.1632.34129 [PubMed 12495173]Kishino S, Koshinami Y, Hosoi T, et al. Effective fluconazole therapy for liver transplant recipients during continuous hemodiafiltration. Ther Drug Monit. 2001;23(1):4-8. [PubMed 11206042]Kotogyan A, Harmanyeri Y, Tahsin Gunes A, et al. Efficacy and safety of oral fluconazole in the treatment of patients with tinea corporis, cruris or pedis or cutaneous candidosis: a multicentre, open, noncomparative study. Clin Drug Investig. 1996;12(2):59-66. doi:10.2165/00044011-199612020-00001 [PubMed 24610666]Kumar S, Bhale G, Brar BK. Symmetrical drug related intertriginous and flexural exanthema (SDRIFE) induced by fluconazole: An uncommon side effect of a commonly used drug. Dermatol Ther. 2019;32(6):e13130. doi:10.1111/dth.13130 [PubMed 31659833]Kyriakidis I, Tragiannidis A, Munchen S, Groll AH. Clinical hepatotoxicity associated with antifungal agents. Expert Opin Drug Saf. 2017;16(2):149-165. doi:10.1080/14740338.2017.1270264 [PubMed 27927037]Lawson C, Karlowsky JA, Zhanel GG. Fluconazole-induced hepatotoxicity: review of published case reports. The Canadian Journal of Hospital Pharmacy. 1998;51(2):61-63.Lee J, Kim HS, Shin SH, et al. Efficacy and safety of fluconazole prophylaxis in extremely low birth weight infants: multicenter pre-post cohort study. BMC Pediatr. 2016;16:67. [PubMed 27184665]Lee JM, Graciano AL, Dabrowski L, Kuzmic B, Tablizo MA. Coccidioidomycosis in infants: A retrospective case series. Pediatr Pulmonol. 2016;51(8):858-862. [PubMed 26829719]Lee JW, Seibel NL, Amantea M, et al. Safety and Pharmaco*kinetics of Fluconazole in Children With Neoplastic Diseases. J Pediatr. 1992;120(6):987-993. [PubMed 1593362]Leonart LP, Tonin FS, Ferreira VL, Tavares da Silva Penteado S, de Araújo Motta F, Pontarolo R. Fluconazole doses used for prophylaxis of invasive fungal infection in neonatal intensive care units: a network meta-analysis. J Pediatr. 2017;185:129-135.e6. doi:10.1016/j.jpeds.2017.02.039 [PubMed 28285752]Leroux S, Jacqz-Aigrain E, Elie V, et al. Pharmaco*kinetics and safety of fluconazole and micafungin in neonates with systemic candidiasis: a randomized, open-label clinical trial. Br J Clin Pharmacol. 2018;84(9):1989-1999. [PubMed 29744900]Li PK, Szeto CC, Piraino B, et al. ISPD peritonitis recommendations: 2016 update on prevention and treatment [published correction appears in Perit Dial Int. 2018;38(4):313]. Perit Dial Int. 2016;36(5):481-508. doi:10.3747/pdi.2016.00078 [PubMed 27282851]Lo Re V 3rd, Carbonari DM, Lewis JD, et al. Oral azole antifungal medications and risk of acute liver injury, overall and by chronic liver disease status. Am J Med. 2016;129(3):283-91.e5. doi:10.1016/j.amjmed.2015.10.029 [PubMed 26597673]Lopez ND, Phillips KM. Fluconazole pharmaco*kinetics in a morbidly obese, critically ill patient receiving continuous venovenous hemofiltration. Pharmacotherapy. 2014;34(9):e162-e168. doi: 0.1002/phar.1470 [PubMed 25074285]Malani PN, McNeil SA, Bradley SF, Kauffman CA. Candida albicans sternal wound infections: a chronic and recurrent complication of median sternotomy. Clin Infect Dis. 2002;35(11):1316-1320. [PubMed 12439793]Martínez-Alonso JC, Domínguez-Ortega FJ, Fuentes-Gonzalo MJ. Urticaria and angioedema due to itraconazole. Allergy. 2003;58(12):1317-1318. doi:10.1046/j.0105-4538.2003.00316.x [PubMed 14616112]Mazuski JE, Tessier JM, May AK, et al. The Surgical Infection Society revised guidelines on the management of intra-abdominal infection. Surg Infect (Larchmt). 2017;18(1):1-76. doi:10.1089/sur.2016.261 [PubMed 28085573]McMahon JH, Grayson ML. Torsades de pointes in a patient receiving fluconazole for cerebral cryptococcosis. Am J Health Syst Pharm. 2008;65(7):619-623. doi:10.2146/ajhp070203 [PubMed 18359968]Miller R, Assi M; AST Infectious Diseases Community of Practice. Endemic fungal infections in solid organ transplant recipients-guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13553. doi:10.1111/ctr.13553 [PubMed 30924967]Molloy SF, Kanyama C, Heyderman RS, et al; ACTA Trial Study Team. Antifungal combinations for treatment of cryptococcal meningitis in Africa. N Engl J Med. 2018;378(11):1004-1017. doi: 10.1056/NEJMoa1710922. [PubMed 29539274]Momper JD, Capparelli EV, Wade KC, et al. Population pharmaco*kinetics of fluconazole in premature infants with birth weights less than 750 grams. Antimicrob Agents Chemother. 2016;60(9):5539-5545. [PubMed 27401564]Monastirli A, Pasmatzi E, Vryzaki E, Georgiou S, Tsambaos D. Fluconazole-induced Stevens-Johnson syndrome in a HIV-negative patient. Acta Derm Venereol. 2008;88(5):521-522. doi:10.2340/00015555-0489 [PubMed 18779900]Montero-Gei F, Perera A. Therapy with fluconazole for tinea corporis, tinea cruris, and tinea pedis. Clin Infect Dis. 1992;14(suppl 1):S77-S81. [PubMed 1562699]Moorhead AM, Amir LH, O'Brien PW, Wong S. A prospective study of fluconazole treatment for breast and nipple thrush. Breastfeed Rev. 2011;19(3):25-29. [PubMed 22263374]Muhl E, Martens T, Iven H, Rob P, Bruch HP. Influence of continuous veno-venous haemodiafiltration and continuous veno-venous haemofiltration on the pharmaco*kinetics of fluconazole. Eur J Clin Pharmacol. 2000;56(9-10):671-678. [PubMed 11214774]Murakami H, Katahira H, Matsushima T, et al. Agranulocytosis during treatment with fluconazole. J Int Med Res. 1992;20(6):492-494. doi:10.1177/030006059202000607 [PubMed 1286742]Nakai N, Katoh N. Fixed drug eruption caused by fluconazole: a case report and mini-review of the literature. Allergol Int. 2013;62(1):139-141. doi:10.2332/allergolint.12-LE-0464 [PubMed 23172357]National Institute for Health and Care Excellence. Drug allergy: diagnosis and management. https://www.nice.org.uk/guidance/cg183/resources/drug-allergy-diagnosis-and-management-pdf-35109811022821. Published September 3, 2014. Accessed April 13, 2021.Nenoff P, Krüger C, Paasch U, Ginter-Hanselmayer G. Mycology - an update part 3: Dermatomycoses: topical and systemic therapy. J Dtsch Dermatol Ges. 2015;13(5):387-410; quiz 411. [PubMed 25918080]Neuhaus G, Pavic N, Pletscher M. Anaphylactic reaction after oral fluconazole. BMJ. 1991;302(6788):1341. doi:10.1136/bmj.302.6788.1341-b [PubMed 2059703]Nozickova M, Koudelkova V, Kulikova Z, Malina L, Urbanowski S, Silney W. A comparison of the efficacy of oral fluconazole, 150 mg/week versus 50 mg/day, in the treatment of tinea corporis, tinea cruris, tinea pedis, and cutaneous candidosis. Int J Dermatol. 1998;37(9):703-705. [PubMed 9762826]Nussbaum JC, Jackson A, Namarika D, et al. Combination flucytosine and high-dose fluconazole compared with fluconazole monotherapy for the treatment of cryptococcal meningitis: a randomized trial in Malawi. Clin Infect Dis. 2010;50(3):338-344. doi:10.1086/649861 [PubMed 20038244]Oualha M, Tréluyer JM, Moshous D, et al. Fluconazole exposure in plasma and bile during continuous venovenous hemodialysis. Ther Drug Monit. 2019;41(4):544-546. doi:10.1097/FTD.0000000000000641 [PubMed 31259879]Oono S, Tabei K, Tetsuka T, Asano Y. The pharmaco*kinetics of fluconazole during haemodialysis in uraemic patients. Eur J Clin Pharmacol. 1992;42(6):667-669. [PubMed 1623910]Pappas PG, Bradsher RW, Kauffman CA, et al; The National Institute of Allergy and Infectious Diseases Mycoses Study Group. Treatment of blastomycosis with higher doses of fluconazole. Clin Infect Dis. 1997;25(2):200-205. [PubMed 9332510]Pappas PG, Kauffman CA, Andes D, et al; Infectious Diseases Society of America. Clinical practice guideline for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;48(5):503-535. doi:10.1086/596757 [PubMed 19191635]Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1-e50. doi:10.1093/cid/civ933 [PubMed 26679628]Pappas PG, Kauffman CA, Perfect J, et al. Alopecia associated with fluconazole therapy. Ann Intern Med. 1995;123(5):354-357. doi:10.7326/0003-4819-123-5-199509010-00006 [PubMed 7625624]Pastick KA, Nalintya E, Tugume L, et al. Cryptococcosis in pregnancy and the postpartum period: Case series and systematic review with recommendations for management. Med Mycol. 2020;58(3):282‐292. doi:10.1093/mmy/myz084 [PubMed 31689712]Patel K, Roberts JA, Lipman J, Tett SE, Deldot ME, Kirkpatrick CM. Population pharmaco*kinetics of fluconazole in critically ill patients receiving continuous venovenous hemodiafiltration: using Monte Carlo simulations to predict doses for specified pharmacodynamic targets. Antimicrob Agents Chemother. 2011;55(12):5868-5873. doi:10.1128/AAC.00424-11 [PubMed 21930888]Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of Cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(3):291-322. doi:10.1086/649858 [PubMed 20047480]Pham CP, de Feiter PW, van der Kuy PH, van Mook WN. Long QTc interval and torsade de pointes caused by fluconazole. Ann Pharmacother. 2006;40(7-8):1456-1461. doi:10.1345/aph.1G741 [PubMed 16849620]Pinto A, Chan RC. Lack of allergic cross-reactivity between fluconazole and voriconazole. Antimicrob Agents Chemother. 2009;53(4):1715-1716. doi:10.1128/AAC.01500-08 [PubMed 19164151]Piper L, Smith PB, Hornik CP, et al. Fluconazole Loading Dose Pharmaco*kinetics and Safety in Infants. Pediatr Infect Dis J. 2011;30(5):375-378. [PubMed 21085048]Poluzzi E, Raschi E, Motola D, Moretti U, De Ponti F. Antimicrobials and the risk of torsades de pointes: the contribution from data mining of the US FDA Adverse Event Reporting System. Drug Saf. 2010;33(4):303-314. doi:10.2165/11531850-000000000-00000 [PubMed 20297862]Quint T, Wöhrl S, Kinaciyan T. Fixed drug eruption caused by fluconazole-An underdiagnosed but recurrent problem. Contact Dermatitis. 2019;80(3):172-173. doi:10.1111/cod.13149 [PubMed 30417394]Refer to manufacturer's labeling.Restrepo C, Chacon J, Manjarres G. Fungal peritonitis in peritoneal dialysis patients: successful prophylaxis with fluconazole as demonstrated by prospective randomized control trial. Perit Dial Int. 2010;30(6):619-625. doi:10.3747/pdi.2008.00189 [PubMed 20634438]Rex JH, Bennett JE, Sugar AM; Candidemia Study Group and the National Institute. A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. N Engl J Med. 1994;331(20):1325-1330. doi:10.1056/NEJM199411173312001 [PubMed 7935701]Rex JH, Pappas PG, Karchmer AW, et al; National Institute of Allergy and Infectious Diseases Mycoses Study Group. A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects. Clin Infect Dis. 2003;36(10):1221-1228. [PubMed 12746765]Rikken B, Hartwig NG, van den Hoek J. Renal candida infection in infants and neonates: report of four cases, review of the literature and treatment proposal. Curr Urol. 2007;1:113-120. doi:10.1159/000115292Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med. 2004;350(10):1013-1022. doi:10.1056/NEJMra032426 [PubMed 14999113]Salem M, Reichlin T, Fasel D, Leuppi-Taegtmeyer A. Torsade de pointes and systemic azole antifungal agents: analysis of global spontaneous safety reports. Glob Cardiol Sci Pract. 2017;2017(2):11. doi:10.21542/gcsp.2017.11 [PubMed 29644223]Scher RK, Breneman D, Rich P, et al. Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the toenail. J Am Acad Dermatol. 1998;38(6, pt 2):S77-S86. doi:10.1016/s0190-9622(98)70490-6 [PubMed 9631989]Schilling CG, Seay RE, Larson TA, Meier KR. Excretion of fluconazole inhuman breast milk [abstract]. Pharmacotherapy. 1993;13(3):287.Schneller-Pavelescu L, Ochando-Ibernón G, Vergara-de Caso E, Silvestre-Salvador JF. Herpes simplex-like fixed drug eruption induced by fluconazole without cross-reactivity to itraconazole. Dermatitis. 2019;30(2):174-175. doi:10.1097/DER.0000000000000451 [PubMed 30829805]Schrijvers R, Gilissen L, Chiriac AM, Demoly P. Pathogenesis and diagnosis of delayed-type drug hypersensitivity reactions, from bedside to bench and back. Clin Transl Allergy. 2015;5:31. doi:10.1186/s13601-015-0073-8 [PubMed 26339470]Science M, Robinson PD, MacDonald T, Rassekh SR, Dupuis LL, Sung L. Guideline for primary antifungal prophylaxis for pediatric patients with cancer or hematopoietic stem cell transplant recipients. Pediatr Blood Cancer. 2014;61(3):393-400. doi:10.1002/pbc.24847 [PubMed 24424789]Sedlak T, Shufelt C, Iribarren C, Lyon LL, Bairey Merz CN. Oral contraceptive use and the ECG: evidence of an adverse QT effect on corrected QT interval. Ann Noninvasive Electrocardiol. 2013;18(4):389-398. doi:10.1111/anec.12050 [PubMed 23879279]Silveira FP, Kusne S; AST Infectious Diseases Community of Practice. Candida infections in solid organ transplantation. Am J Transplant. 2013;13(suppl 4):220-227. doi:10.1111/ajt.12114 [PubMed 23465015]Singh Mahal H. Fluconazole-induced type 1 kounis syndrome. Am J Ther. 2016;23(3):e961-e962. doi:10.1097/MJT.0000000000000113 [PubMed 26938747]Singh N, Huprikar S, Burdette SD, Morris MI, Blair JE, Wheat LJ; American Society of Transplantation, Infectious Diseases Community of Practice, Donor-Derived Fungal Infection Working Group. Donor-derived fungal infections in organ transplant recipients: guidelines of the American Society of Transplantation, Infectious Diseases Community of Practice. Am J Transplant. 2012;12(9):2414-2428. [PubMed 22694672]Sinnollareddy MG, Roberts MS, Lipman J, Robertson TA, Peake SL, Roberts JA. Pharmaco*kinetics of fluconazole in critically ill patients with acute kidney injury receiving sustained low-efficiency diafiltration. Int J Antimicrob Agents. 2015;45(2):192-195. doi:10.1016/j.ijantimicag.2014.08.013 [PubMed 25455854]Sobel JD, Wiesenfeld HC, Martens M, et al. Maintenance fluconazole therapy for recurrent vulvovagin*l candidiasis. N Engl J Med. 2004;351(9):876-883. doi:10.1056/NEJMoa033114 [PubMed 15329425]Sobel JD. Candida vulvovaginitis: treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 27, 2021.Song JC, Deresinski S. Hepatotoxicity of antifungal agents. Curr Opin Investig Drugs. 2005;6(2):170-177. [PubMed 15751740]Spellberg B, Rieg G, Bayer A, Edwards JE Jr. Lack of cross-hepatotoxicity between fluconazole and voriconazole. Clin Infect Dis. 2003;36(8):1091-1093. doi:10.1086/374255 [PubMed 12684933]Spernovasilis N, Kofteridis DP. Pre-existing liver disease and toxicity of antifungals. J Fungi (Basel). 2018;4(4):133. doi:10.3390/jof4040133 [PubMed 30544724]Stary A, Sarnow E. Fluconazole in the treatment of tinea corporis and tinea cruris. Dermatology. 1998;196(2):237-241. doi: 10.1159/000017881. [PubMed 9568414]Stengel F, Robles-Soto M, Galimberti R, Suchil P. Fluconazole versus ketoconazole in the treatment of dermatophytoses and cutaneous candidiasis. Int J Dermatol. 1994;33(10):726-729. [PubMed 8002145]Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis. 2014;59(2):e10-52. doi: 10.1093/cid/ciu296. [PubMed 24947530]Su FW, Perumalswami P, Grammer LC. Acute hepatitis and rash to fluconazole. Allergy. 2003;58(11):1215-1216. doi:10.1046/j.0105-4538.2003.00318.x [PubMed 14616149]Takahashi T, Hitani A, Yamada H, Nakamura T, Iwamoto A. Desenitization to fluconazole in an AIDS patient. Ann Pharmacother. 2001;35(5):642-643. doi:10.1345/aph.10285 [PubMed 11346073]Taplitz RA, Kennedy EB, Bow EJ, et al. Antimicrobial prophylaxis for adult patients with cancer-related immunosuppression: ASCO and IDSA clinical practice guideline update [published online ahead of print September 4, 2018]. J Clin Oncol. doi:10.1200/JCO.18.00374 [PubMed 30179565]Tholakanahalli VN, Potti A, Hanley JF, Merliss AD. Fluconazole-induced torsade de pointes. Ann Pharmacother. 2001;35(4):432-434. doi:10.1345/aph.10210 [PubMed 11302406]Thompson GR 3rd, Krois CR, Affolter VK, et al. Examination of fluconazole-induced alopecia in an animal model and human cohort. Antimicrob Agents Chemother. 2019;63(2):e01384-18. doi:10.1128/AAC.01384-18 [PubMed 30455235]Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Can Pharm J (Ott). 2016;149(3):139-152. doi:10.1177/1715163516641136 [PubMed 27212965]Tisdale JE, Chung MK, Campbell KB, et al. Drug-induced arrhythmias: a scientific statement from the American Heart Association. Circulation. 2020;142(15):e214-e233. doi:10.1161/CIR.0000000000000905 [PubMed 32929996]Tisdale JE, Jaynes HA, Kingery JR, et al. Development and validation of a risk score to predict QT interval prolongation in hospitalized patients. Circ Cardiovasc Qual Outcomes. 2013;6(4):479-487. doi:10.1161/CIRCOUTCOMES.113.000152 [PubMed 23716032]Tomblyn M, Chiller T, Einsele H, et al; Center for International Blood and Marrow Research; National Marrow Donor Program; American Society of Blood and Marrow Transplantation; et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15(10):1143-1238. doi:10.1016/j.bbmt.2009.06.019 [PubMed 19747629]Toon S, Ross CE, Gokal R, Rowland M. An assessment of the effects of impaired renal function and haemodialysis on the pharmaco*kinetics of fluconazole. Br J Clin Pharmacol. 1990;29(2):221-226. [PubMed 2306414]Trotman RL, Williamson JC, Shoemaker DM, Salzer WL. Antibiotic dosing in critically ill adult patients receiving continuous renal replacement therapy. Clin Infect Dis. 2005;41(8):1159-1166. doi:10.1086/444500 [PubMed 16163635]Tunkel AR, Hasbun R, Bhimraj A, et al. 2017 Infectious Diseases Society of America's clinical practice guidelines for healthcare-associated ventriculitis and meningitis. Clin Infect Dis. 2017;64(6):e34-e65. doi:10.1093/cid/ciw861 [PubMed 28203777]Tverdek FP, Kofteridis D, Kontoyiannis DP. Antifungal agents and liver toxicity: a complex interaction. Expert Rev Anti Infect Ther. 2016;14(8):765-776. doi:10.1080/14787210.2016.1199272 [PubMed 27275514]US Department of Health and Human Services (HHS); Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. http://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf. Updated September 2016. Accessed October 5, 2016.US Department of Health and Human Services (HHS) Panel Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-oi/guidelines-adult-adolescent-oi.pdf. Updated February 17, 2022. Accessed February 24, 2022.US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Guidelines for the prevention and treatment of opportunistic infections among HIV-exposed and HIV-infected children: recommendations from the National Institutes of Health, Centers for Disease Control and Prevention, the HIV Medicine Association of the Infectious Diseases Society of America and the Pediatric Infectious Diseases Society. July 2018. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/OI_Guidelines_Pediatrics.pdf.US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children. Department of Health and Human Services. https://clinicalinfo.hiv.gov/en/guidelines/pediatric-opportunistic-infection/whats-new. Updated January 23, 2020. Accessed April 19, 2021.US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious DiseasesSociety of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. May 2018.US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed April 30, 2020.US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/Adult_OI.pdf. Updated June 11, 2021. Accessed January 31, 2022.Valtonen M, Tiula E, Neuvonen PJ. Effect of continuous venovenous haemofiltration and haemodiafiltration on the elimination of fluconazole in patients with acute renal failure. J Antimicrob Chemother. 1997;40(5):695-700. [PubMed 9421318]Van Daele R, Wauters J, Lagrou K, et al. Pharmaco*kinetic variability and target attainment of fluconazole in critically ill patients. Microorganisms. 2021;9(10):2068. doi:10.3390/microorganisms9102068 [PubMed 34683388]van der Elst KC, Pereboom M, van den Heuvel ER, Kosterink JG, Schölvinck EH, Alffenaar JW. Insufficient fluconazole exposure in pediatric cancer patients and the need for therapeutic drug monitoring in critically ill children. Clin Infect Dis. 2014;59(11):1527-1533. doi:10.1093/cid/ciu657 [PubMed 25148892]Vas S, Oreopoulos DG. Infections in patients undergoing peritoneal dialysis. Infect Dis Clin North Am. 2001;15(3):743-774. [PubMed 11570140]Vazquez JA. Management of candidemia and invasive candidiasis in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 27, 2022.Veltri MA, Neu AM, Fivush BA, Parekh RS, Furth SL. Drug dosing during intermittent hemodialysis and continuous renal replacement therapy: special considerations in pediatric patients. Paediatr Drugs. 2004;6(1):45-65. [PubMed 14969569]Vivjoa (oteseconazole) [prescribing information]. Durham, NC: Mycovia Pharmaceuticals Inc; April 2022.Wade KC, Benjamin DK Jr, Kaufman DA, et al. Fluconazole Dosing for the Prevention or Treatment of Invasive Candidiasis in Young Infants. Pediatr Infect Dis J. 2009;28(8):717-723. [PubMed 19593252]Wang AY, Yu AW, Li PK, Leung CB, Lai KN, Lui SE. Factors predicting outcome of fungal peritonitis in peritoneal dialysis: analysis of a 9-year experience of fungal peritonitis in a single center. Am J Kidney Dis. 2000;36(6):1183-1192. doi:10.1053/ajkd.2000.19833 [PubMed 11096043]Wang JL, Chang CH, Young-Xu Y, Chan KA. Systematic review and meta-analysis of the tolerability and hepatotoxicity of antifungals in empirical and definitive therapy for invasive fungal infection. Antimicrob Agents Chemother. 2010;54(6):2409-2419. doi:10.1128/AAC.01657-09 [PubMed 20308378]Warady BA, Bakkaloglu S, Newland J, et al. Consensus guideline for the prevention and treatment of catheter-related infections and peritonitis in pediatric patients receiving peritoneal dialysis: 2012. Peritoneal Dialysis International. 2012;32:s32-86. [PubMed 22851742]Wassmann S, Nickenig G, Bohm M. Long QT syndrome and torsade de pointes in a patient receiving fluconazole. Ann Inter Med. 1999;131(10):797. [PubMed 10577320]Watt KM, Benjamin DK Jr, Cheifetz IM, et al. Pharmaco*kinetics and safety of fluconazole in young infants supported with extracorporeal membrane oxygenation. Pediatr Infect Dis J. 2012;31(10):1042-1047. [PubMed 22627870]Watt KM, Cohen-Wolkowiez M, Barrett JS, et al. Physiologically based pharmaco*kinetic approach to determine dosing on extracorporeal life support: fluconazole in children on ECMO. CPT Pharmacometrics Syst Pharmacol. 2018;7(10):629-637. doi:10.1002/psp4.12338 [PubMed 30033691]Watt KM, Gonzalez D, Benjamin DK Jr, et al. Fluconazole population pharmaco*kinetics and dosing for prevention and treatment of invasive Candidiasis in children supported with extracorporeal membrane oxygenation. Antimicrob Agents Chemother. 2015;59(7):3935-3943. doi:10.1128/AAC.00102-15 [PubMed 25896706]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007;45(7):807-825. [PubMed 17806045]Wingard JR. Prophylaxis of invasive fungal infection in adults with hematologic malignancies. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 9, 2019.Winston DJ, Busuttil RW. Randomized controlled trial of oral itraconazole solution versus intravenous/oral fluconazole for prevention of fungal infections in liver transplant recipients. Transplantation. 2002;74(5):688-695. doi: 10.1097/01.TP.0000019727.88291.F5. [PubMed 12352887]Wong SF, Leung MP, Chan MY. Pharmaco*kinetics of fluconazole in children requiring peritoneal dialysis. Clin Ther. 1997;19(5):1039-1047. doi:10.1016/s0149-2918(97)80056-2 [PubMed 9385491]World Health Organization (WHO). Breastfeeding and maternal medication, recommendations for drugs in the Eleventh WHO Model List of Essential Drugs. http://www.who.int/maternal_child_adolescent/documents/55732/en/. Published 2002.World Health Organization (WHO). Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV. https://www.who.int/publications/i/item/9789240052178. Published June 27, 2022. Accessed October 16, 2022.Workowski KA, Bachmann LH, Chan PA, et al; Centers for Disease Control and Prevention (CDC). Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1-187. doi:10.15585/mmwr.rr7004a1 [PubMed 34292926]Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015 [published correction appears in MMWR Recomm Rep. 2015;64(33):924]. MMWR Recomm Rep. 2015;64(RR-03):1-137. [PubMed 26042815]Zeuli JD, Wilson JW, Estes LL. Effect of combined fluoroquinolone and azole use on QT prolongation in hematology patients. Antimicrob Agents Chemother. 2013;57(3):1121-1127. doi:10.1128/AAC.00958-12 [PubMed 23229485]Topic 13303 Version 628.0

CloseSpironolactone: Pediatric drug informationSpironolactone: Pediatric drug information(For additional information see "Spironolactone: Drug information" and see "Spironolactone: Patient drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USAldactone;CaroSpirBrand Names: CanadaAldactone;JAMP-Spironolactone;MINT-Spironolactone;TEVA-SpironolactoneTherapeutic CategoryAntihypertensive Agent;Diuretic, Potassium SparingDosing: NeonatalNote: Although spironolactone is commercially available in a suspension, it is NOT therapeutically equivalent to the tablets; commercially available suspension results in 15% to 37% higher serum concentration compared to the tablet; pediatric dosing is based on experience with tablets and extemporaneously compounded suspension. Multiple concentrations of oral suspension exist; use extra precaution and prescribe in mg (not mL).Bronchopulmonary dysplasia (BPD): Limited data available; efficacy results variable. Although the benefits of diuretic therapy in the management of BPD are variable (eg, optimal duration of therapy, impact on pulmonary endpoints), diuretics continue to be used in clinical practice (Ref): Oral: 1.5 mg/kg/dose every 12 hours; used in combination with a thiazide diuretic (Ref); used most often in preterm neonates at a PNA >28 days (Ref)Edema (diuresis): Limited data available: Oral: 1 to 3 mg/kg/day in divided doses every 12 to 24 hours; used in combination with a thiazide diuretic (Ref)Dosing adjustment in renal impairment: Spironolactone is substantially excreted by the kidney; use with caution; monitor serum potassium closely; consider extended dosing intervals (eg, every 24 to 48 hours) for moderate renal impairment; avoid use in severe renal impairment (Ref)Dosing: PediatricNote: Although spironolactone is commercially available in a suspension, it is NOT therapeutically equivalent to the tablets; commercially available suspension results in 15% to 37% higher serum concentration compared to the tablet; pediatric dosing is based on experience with tablets and extemporaneously compounded suspension. Multiple concentrations of oral suspension exist; use extra precaution and prescribe in mg (not mL).Bronchopulmonary dysplasiaBronchopulmonary dysplasia (BPD): Limited data available; efficacy results variable. Although the benefits of diuretic therapy in the management of BPD are variable (eg, optimal duration of therapy, impact on pulmonary endpoints), diuretics continue to be used in clinical practice (Ref). Infants: Oral: 1.5 mg/kg/dose every 12 hours (Ref).EdemaEdema (diuresis): Limited data available: Infants, Children, and Adolescents: Oral: Initial: 1 to 3 mg/kg/day divided every 6 to 24 hours; titrate as needed; reported maximum daily dose range: 4 to 6 mg/kg/day in divided doses every 6 to 12 hours or 400 mg/day, whichever is less (Ref)HypertensionHypertension: Limited data available: Infants, Children, and Adolescents: Oral: Initial: 1 mg/kg/day divided every 12 to 24 hours; titrate as needed up to a maximum daily dose: 3.3 mg/kg/day or 100 mg/day, whichever is less (Ref)Primary aldosteronism, treatmentPrimary aldosteronism (caused by adrenal hyperplasia), treatment: Limited data available: Infants, Children, and Adolescents: Oral: 1 to 3 mg/kg/day; maximum daily dose: 100 mg/day (Ref)Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricThere are no dosage adjustments provided in the manufacturer's labeling; spironolactone is substantially excreted by the kidney; use with caution; monitor serum potassium closely. The following recommendations have been suggested: In pediatric patients with mild to moderate failure, consider extended dosing interval (eg, every 12 to 24 hours) and avoid use in severe renal impairment (Ref).Dosing: Hepatic Impairment: PediatricThere are no dosage adjustments provided in the manufacturer's labeling. Use with caution; minor alterations of fluid and electrolyte balance may precipitate hepatic coma.Dosing: Adult(For additional information see "Spironolactone: Drug information")Note: Suspension is not therapeutically equivalent to tablets. Suspension results in 15% to 37% higher serum concentration compared to tablets. Doses of suspension >100 mg may result in higher than expected serum concentrations. In patients requiring >100 mg/dose, use tablets only.Acne vulgaris, females, moderate to severeAcne vulgaris, females, moderate to severe (alternative agent) (off-label use): Tablet: Oral: Initial: 25 to 50 mg/day in 1 to 2 divided doses; titrate as needed based on response and tolerability to a usual effective dose of 50 to 100 mg/day in 1 to 2 divided doses; maximum dose: 200 mg/day (Ref).Ascites due to cirrhosisAscites due to cirrhosis:Note: Generally used in combination with furosemide, but may be used as monotherapy for patients with hypokalemia. For combination therapy, a dosing ratio of spironolactone 100 mg to furosemide 40 mg should generally be maintained, but can be adjusted for electrolyte abnormalities (Ref).Tablet: Oral: Initial: 100 mg once daily; titrate every 3 to 5 days based on response and tolerability; usual maximum dose: 400 mg once daily (Ref). For small-volume ascites in patients who weigh ≤50 kg, some experts recommend a starting dose of 50 mg once daily (Ref).Heart failureHeart failure:Note: When initiating therapy, verify the following: serum creatinine ≤2.5 mg/dL in men and ≤2 mg/dL in women or eGFR >30 mL/minute/1.73 m2 and serum potassium <5 mEq/L. Monitor closely and if patient develops hyperkalemia (serum potassium >5 mEq/L), reduce the dose, change to every-other-day dosing, or discontinue therapy; assess for other causes of hyperkalemia before permanent discontinuation. If renal function worsens, consider dose reduction or discontinuation (Ref).Heart failure with preserved ejection fraction (off-label use):Note: For use in patients with symptomatic heart failure with preserved ejection fraction (HFpEF) (≥45%) who have an elevated serum natriuretic peptide level or have been hospitalized for heart failure in the last 12 months (Ref). Some experts are more conservative regarding serum potassium for patients with HFpEF. They recommend initiating therapy or uptitrating the dose only if serum potassium is ≤4.7 mEq/L and eGFR is ≥30 mL/minute/1.73 m2. They recommend dose reduction or discontinuation if serum potassium is >5 mEq/L (Ref).Tablet: Oral: Initial: 12.5 mg once daily; may double the dose every 2 to 4 weeks if serum potassium and renal function are stable, up to a maximum target dose of 50 mg/day in 1 or 2 divided doses (Ref).Heart failure with reduced ejection fraction: Note: Should be considered for use in patients with symptomatic (New York Heart Association class II to IV) heart failure with reduced ejection fraction (HFrEF) (≤35%) as part of an optimal medical regimen for HFrEF (Ref).Tablet: Oral: Initial: 12.5 to 25 mg once daily; may double the dose every 4 weeks if serum potassium remains <5 mEq/L and renal function is stable, up to a maximum target dose of 50 mg/day in 1 to 2 divided doses (Ref).Suspension: Oral: Initial: 10 to 20 mg once daily. Consider a starting dose of 10 mg once daily in patients at increased risk of hyperkalemia. May titrate to 37.5 mg once daily if serum potassium remains <5 mEq/L and renal function is stable (Ref).Post-myocardial infarction, complicated by reduced ejection fraction (off-label use):Note: Should be considered for use following acute myocardial infarction (MI) in patients with left ventricular ejection fraction ≤40% plus symptoms of heart failure or diabetes. Use in addition to other pharmacologic therapies post MI (Ref).Tablet: Oral: Initial: 12.5 to 25 mg once daily; may double the dose every 4 weeks if serum potassium remains <5 mEq/L and renal function is stable, up to a maximum target dose of 50 mg/day in 1 to 2 divided doses (Ref).Suspension: Oral: Initial: 10 to 20 mg once daily. Consider a starting dose of 10 mg once daily in patients at increased risk of hyperkalemia. May titrate to 37.5 mg once daily if serum potassium remains <5 mEq/L and renal function is stable (Ref).Hirsutism, femalesHirsutism, females (alternative agent) (off-label use): Note: Typically given in addition to oral contraceptives (OCs) if inadequate response to OCs is observed after 6 months. May be considered as initial therapy for females who cannot conceive or who are using reliable contraception (Ref).Tablet: Oral: Initial: 50 mg twice daily; may increase to 100 mg twice daily as needed. Assess response at 6-month intervals before adjusting dose, adding additional agents, or switching to alternative therapy (Ref).Hormone therapy for transgender females, assigned male at birthHormone therapy for transgender females, assigned male at birth (adjunctive agent) (off-label use): Tablet: Oral: Initial: 25 mg once or twice daily in combination with other appropriate agents. Increase at 1-week intervals based on response and tolerability to a usual dose of 100 to 300 mg/day in 2 divided doses; maximum dose: 400 mg/day. Adjust dose with a goal of suppressing serum testosterone levels into the normal range for females (<50 ng/dL) (Ref).Hypertension, chronicHypertension, chronic (alternative agent):Note: Not recommended for initial management but may be considered as additional therapy for resistant hypertension in patients who do not respond adequately to combination therapy with preferred agents (Ref).Tablet: Oral: Initial: 25 mg once daily; titrate as needed after ~2 to 4 weeks based on response and tolerability up to 100 mg once daily (Ref). Some experts recommend a starting dose of 12.5 mg once daily and generally do not exceed 50 mg once daily in the absence of primary aldosteronism (Ref). Patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication titration within 1 week (Ref).Suspension: Oral: Initial: 20 mg/day in 1 or 2 divided doses; titrate as needed after ~2 to 4 weeks based on response and tolerability up to 75 mg/day in 1 or 2 divided doses. Patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication titration within 1 week (Ref).Primary aldosteronismPrimary aldosteronism:Tablet: Oral: Initial: 12.5 to 25 mg once daily (Ref); gradually titrate to the lowest effective dose; usual maximum dose: 400 mg/day (Ref). For surgical candidates, the last dose should be administered the day of surgery; discontinue spironolactone on postoperative day 1 (Ref).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultThe renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.Note: Use with caution; monitor potassium prior to initiating spironolactone and closely during therapy. In circ*mstances where treatment with spironolactone is considered necessary, interventions such as dietary counseling on a low potassium diet, loop diuretics, sodium bicarbonate to correct metabolic acidosis, and prescribing daily GI cation exchangers (eg, patiromer, zirconium cyclosilicate) have been utilized (Ref).Altered kidney function:Tablet:Ascites due to cirrhosis; hypertension; primary aldosteronism: There are no specific dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.Heart failure:eGFR >50 mL/minute/1.73 m2: No initial dosage adjustment necessary.eGFR 30 to 50 mL/minute/1.73 m2: Initial: 12.5 mg once daily or every other day; may double the dose every 4 weeks if serum potassium remains <5 mEq/L and renal function is stable, up to a maximum target dose of 25 mg/day (Ref).eGFR <30 mL/minute/1.73 m2: Use not recommended (Ref); heart failure clinical trials excluded patients with serum creatinine ≥2.5 mg/dL (Ref).Suspension:Ascites due to cirrhosis; hypertension: There are no dosage adjustments provided in the manufacturer's labeling.Heart failure:eGFR >50 mL/minute/1.73 m2: No initial dosage adjustment necessary.eGFR 30 to 50 mL/minute/1.73 m2: Initial: 10 mg once daily.eGFR <30 mL/minute/1.73 m2: Use not recommended (Ref); heart failure clinical trials excluded patients with serum creatinine ≥2.5 mg/dL (Ref).Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzed (Ref):Tablet: Not routinely recommended, but 2 small trials have demonstrated the safety of spironolactone in patients with end-stage kidney disease receiving dialysis (Ref), with a suggested maximum of 25 mg once daily (Ref). Start at lowest initial dose (eg, 12.5 mg daily or every other day) and only utilize if benefits outweigh the risks, potassium is well-controlled, and patients can be monitored closely for hyperkalemia (Ref).Peritoneal dialysis: Unlikely to be significantly dialyzed given high degree of protein binding (Ref):Tablet: Not routinely recommended, but 2 small trials have demonstrated the safety of doses up to 25 mg once daily in patients receiving peritoneal dialysis (Ref). Start at lowest initial dose (eg, 12.5 mg daily or every other day) and only utilize if benefits outweigh the risks, potassium is well-controlled, and patients can be monitored closely for hyperkalemia (Ref).Dosing: Hepatic Impairment: AdultThere are no specific dosage adjustments provided in the manufacturer's labeling; initiate with low dose and titrate slowly (cirrhosis). Use with caution; minor alterations of fluid and electrolyte balance may precipitate hepatic coma.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Suspension, Oral: CaroSpir: 25 mg/5 mL (5 mL) [contains saccharin sodium]CaroSpir: 25 mg/5 mL (118 mL, 473 mL) [contains saccharin sodium; banana flavor]Tablet, Oral: Aldactone: 25 mgAldactone: 50 mg, 100 mg [scored]Generic: 25 mg, 50 mg, 100 mgGeneric Equivalent Available: USMay be product dependentDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Tablet, Oral: Aldactone: 25 mg, 100 mgGeneric: 25 mg, 100 mgAdministration: PediatricOral: May be taken with or without food; however, consistent administration with or without food is preferred to minimize fluctuations in drug exposure.Administration: AdultOral:Tablet: Administer with or without food; however, administer consistently with respect to food.Suspension: Shake well before administering dose. Administer with or without food; however, administer consistently with respect to food.Hazardous Drugs Handling ConsiderationsHazardous agent (NIOSH 2016 [group 2]).Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.NIOSH recommends single gloving for administration of intact tablets or capsules. If manipulating tablets/capsules (eg, to prepare an oral suspension), NIOSH recommends double gloving, a protective gown, and preparation in a controlled device; if not prepared in a controlled device, respiratory and eye/face protection as well as ventilated engineering controls are recommended. NIOSH recommends double gloving, a protective gown, and (if there is a potential for vomit or spit up) eye/face protection for administration of an oral liquid/feeding tube administration (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).Storage/StabilityTablet: Store below 25°C (77°F).Suspension: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).UseAldactone and similar generics: Management of edema and sodium retention associated with heart failure unresponsive to other therapies, cirrhosis of liver accompanied by edema and/or ascites, or nephrotic syndrome unresponsive to other therapies; increase survival and to reduce hospitalization for severe heart failure (New York Heart Association class III to IV) when used in addition to standard therapy; management of hypertension unresponsive to other therapies; treatment of hypokalemia unresponsive to other therapies; prophylaxis of hypokalemia in patients taking digitalis; diagnose primary hyperaldosteronism by therapeutic trial; short-term preoperative treatment of primary hyperaldosteronism; long-term maintenance therapy for patients with discrete aldosterone-producing adrenal adenomas who are judged to be poor operative risks or who decline surgery; and long-term maintenance therapy for bilateral micro- or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism) (All indications: FDA approved in adults)CaroSpir: Treatment of edema associated with cirrhosis of liver, increase survival and to reduce hospitalization for severe heart failure (New York Heart Association class III to IV) when used in addition to standard therapy, and management of hypertension unresponsive to other therapies (All indications: FDA approved in adults)Medication Safety IssuesSound-alike/look-alike issues:Aldactone may be confused with Aldactazide.Older Adult: High-Risk Medication:Beers Criteria: Diuretics (spironolactone) are identified in the Beers Criteria as potentially inappropriate medications to be used with caution in patients 65 years and older due to the potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium concentration closely when initiating or adjusting the dose in older adults (Beers Criteria [AGS 2019]).International issues:Aldactone: Brand name for spironolactone [US, Canada, multiple international markets], but also the brand name for potassium canrenoate [Austria, Czech Republic, Germany, Hungary, Poland].Aldactone [US, Canada, multiple international markets] may be confused with Aldomet brand name for methyldopa [multiple international markets].Adverse Reactions (Significant): ConsiderationsGynecomastiaSpironolactone may cause gynecomastia in patients of any age that may affect one or both breasts (typically both) (Ref). Gynecomastia is usually reversible following discontinuation of therapy (Ref). Eplerenone, which is associated with a lower risk of gynecomastia, may be considered if continued aldosterone antagonist therapy is required (Ref).Mechanism: Dose- and time-related; due to decreased androgen production, inhibition of androgen receptor binding, displacement of estradiol from sex hormone-binding globulin and enhanced peripheral conversion of testosterone to estradiol (Ref).Onset: Delayed; may occur after 1 to 2 months to over a year of therapyRisk factors:• Higher doses (eg, ≥150 mg/day) (Ref)• Longer duration of therapy (Ref)HyperkalemiaSpironolactone may cause reversible hyperkalemia, which may result in hospitalization and in some cases death (Ref).Mechanism: Dose-related; related to the pharmacologic action. Competes with aldosterone for binding to the mineralocorticoid receptor, thereby inhibiting the exchange of sodium for potassium in the distal convoluted renal tubule and preventing potassium excretion.Onset: Intermediate; usually occurs within 4 weeks of initiation or dose titration (Ref).Risk factors:• Older age (Ref)• Kidney impairment (Ref)• Excessive potassium intake (eg, potassium supplements, potassium-containing salt substitutes)• Concomitant use of certain drugs (eg, angiotensin-converting enzyme [ACE] inhibitors, angiotensin-receptor blockers, drospirenone, nonsteroidal anti-inflammatory drugs) (Ref). Concurrent use of larger doses of ACE inhibitors (eg, lisinopril ≥10 mg daily in adults) also increases risk (Ref).• Heart failure (especially patients receiving higher doses and patients with diabetes mellitus, higher baseline serum potassium levels, and worse New York Heart Association functional class) (Ref)Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.1% to 10%: Endocrine & metabolic: Gynecomastia (9%; up to 52% in patients receiving high doses [eg, ≥150 mg/day]) (Haynes 2009; Jeunemaitre 1987; Nuttall 2015; Prisant 2005)Frequency not defined:Cardiovascular: VasculitisDermatologic: Chloasma, erythematous maculopapular rash, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticariaEndocrine & metabolic: Amenorrhea (Levitt 1970), decreased libido, hyperglycemia, hypocalcemia, hypomagnesemia, hyponatremia, hypovolemiaGastrointestinal: Abdominal cramps, diarrhea, gastritis, gastrointestinal hemorrhage, gastrointestinal ulcer, nausea, vomitingGenitourinary: Erectile dysfunction, irregular menses, mastalgia, postmenopausal bleedingHematologic & oncologic: Agranulocytosis (Whitling 1997), leukopenia, thrombocytopeniaHepatic: HepatotoxicityHypersensitivity: AnaphylaxisImmunologic: Drug reaction with eosinophilia and systemic symptomsNervous system: Ataxia, confusion, dizziness, drowsiness, headache, lethargy, nipple painNeuromuscular & skeletal: Lower limb crampRenal: Renal failure syndrome, renal insufficiencyMiscellaneous: FeverPostmarketing: Endocrine & metabolic: Gout (Ben Salem 2017), hyperkalemia (common: ≥10%) (Huang 2005; Shah 2005), hyperuricemia (Ben Salem 2017), metabolic acidosis (in patients with cirrhosis) (Feinfeld 1978; Gabow 1979), ovarian cyst (in a premature neonate) (Vachharajani 2001)ContraindicationsHyperkalemia; Addison disease; concomitant use with eplerenone.Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to spironolactone or any component of the formulation; acute renal insufficiency; severe renal impairment (eGFR <30 mL/minute/1.73 m2); anuria; concomitant use with heparin or low molecular weight heparin; pregnancy; breastfeeding.Warnings/PrecautionsConcerns related to adverse effects:• Fluid/electrolyte imbalance: Fluid and electrolyte imbalance (eg, hypomagnesemia, hyponatremia, hypocalcemia, hyperglycemia, hyperkalemia) may occur. Patients with heart failure, renal disease, or cirrhosis may be particularly susceptible. Monitor and correct electrolyte disturbances; adjust dose to avoid dehydration.• Tumorigenic: Shown to be a tumorigen in chronic toxicity animal studies. Recent retrospective and observational studies do not suggest an increased risk of prostate or breast cancer (McKenzie 2016; Rozner 2020; Sabatier 2019).Disease-related concerns:• Adrenal vein catheterization: Discontinue use prior to adrenal vein catheterization.• Heart failure: When evaluating a heart failure patient for spironolactone treatment, eGFR should be >30 mL/minute/1.73 m2 or creatinine should be ≤2.5 mg/dL (men) or ≤2 mg/dL (women) with no recent worsening and potassium <5 mEq/L with no history of severe hyperkalemia (ACCF/AHA [Yancy 2013]). Serum potassium levels require close monitoring and management if elevated. American College of Cardiology/American Heart Association recommends considering discontinuation upon the development of serum potassium >5.5 mEq/L or worsening renal function with careful evaluation of the entire medical regimen. Avoid triple therapy with the combined use of an ACE inhibitor, ARB, and spironolactone. Therapy may need to be modified during an episode of diarrhea or dehydration or when loop diuretic therapy is interrupted (ACCF/AHA [Yancy 2013]).Special populations:• Older adult: Avoid use of tablets >25 mg/day in older adult patients with heart failure or with reduced renal function (eg, CrCl <30 mL/minute or eGFR ≤30 mL/minute/1.73 m2 [ACCF/AHA (Yancy 2013)]).Other warnings/precautions:• Suspension: Suspension is NOT therapeutically equivalent to tablets. In patients requiring >100 mg/dose, use tablets (>100 mg/dose of suspension may result in spironolactone concentration higher than expected).Metabolism/Transport EffectsNone known.Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions programAbiraterone Acetate: Spironolactone may diminish the therapeutic effect of Abiraterone Acetate.Risk C: Monitor therapyAlfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyAlpha-/Beta-Agonists: Spironolactone may diminish the vasoconstricting effect of Alpha-/Beta-Agonists.Risk C: Monitor therapyAmifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine.Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modificationAMILoride: May enhance the hyperkalemic effect of Spironolactone. Risk X: Avoid combinationAmmonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis.Risk C: Monitor therapyAmphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapyAngiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapyAngiotensin-Converting Enzyme Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors.Risk C: Monitor therapyAntipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]).Risk C: Monitor therapyAspirin: May diminish the therapeutic effect of Spironolactone. Risk C: Monitor therapyAtorvastatin: May enhance the adverse/toxic effect of Spironolactone. Specifically, there is a theoretical potential for enhanced effects on reducing endogenous steroid activity. Risk C: Monitor therapyBarbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyBenperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyBrigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapyBrimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyBromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combinationCholestyramine Resin: May enhance the adverse/toxic effect of Spironolactone. Specifically, the risks of developing metabolic acidosis and hyperkalemia may be elevated with this combination. Risk C: Monitor therapyCiprofloxacin (Systemic): Spironolactone may enhance the arrhythmogenic effect of Ciprofloxacin (Systemic).Risk C: Monitor therapyCosyntropin: Spironolactone may diminish the diagnostic effect of Cosyntropin.Management: Patients receiving spironolactone should omit their pre-test dose on the day selected for cosyntropin testing. Risk D: Consider therapy modificationCycloSPORINE (Systemic): Potassium-Sparing Diuretics may enhance the hyperkalemic effect of CycloSPORINE (Systemic).Risk X: Avoid combinationCYP2C8 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Spironolactone may increase the serum concentration of CYP2C8 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors).Risk C: Monitor therapyCYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Spironolactone may increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors).Risk C: Monitor therapyDesmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin.Risk C: Monitor therapyDexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapyDiacerein: May enhance the therapeutic effect of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased. Risk C: Monitor therapyDiazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyDigoxin: Spironolactone may increase the serum concentration of Digoxin. Spironolactone (and/or its metabolites) may also interfere with the assays used to determine Digoxin concentrations, falsely increasing or decreasing Digoxin concentrations.Risk C: Monitor therapyDrospirenone-Containing Products: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapyDULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine.Risk C: Monitor therapyEplerenone: Spironolactone may enhance the hyperkalemic effect of Eplerenone.Risk X: Avoid combinationFinerenone: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of Finerenone.Risk C: Monitor therapyFludrocortisone: May diminish the therapeutic effect of Mineralocorticoid (Aldosterone) Receptor Antagonists. Mineralocorticoid (Aldosterone) Receptor Antagonists may diminish the therapeutic effect of Fludrocortisone. Risk C: Monitor therapyFlunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapyHeparin: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: Monitor serum potassium concentrations closely. The spironolactone Canadian product monograph lists its combination with heparin or low molecular weight heparins as contraindicated. Risk C: Monitor therapyHeparins (Low Molecular Weight): May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: Monitor serum potassium concentrations closely. The spironolactone Canadian product monograph lists its combination with heparin or low molecular weight heparins as contraindicated. Risk C: Monitor therapyHerbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapyHerbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyHypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents.Risk C: Monitor therapyLevodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products.Risk C: Monitor therapyLoop Diuretics: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapyLormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyMethylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapyMitotane: Spironolactone may decrease the serum concentration of Mitotane.Risk C: Monitor therapyMolsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyNaftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyNicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyNicorandil: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapyNicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyNitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside.Risk C: Monitor therapyNonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapyObinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modificationOpioid Agonists: May enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Risk C: Monitor therapyPentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyPholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine.Risk C: Monitor therapyPhosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyPotassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: Avoid coadministration of a potassium-sparing diuretic and a potassium salt. This combination should only be used in cases of significant hypokalemia, and only if serum potassium can be closely monitored. Risk D: Consider therapy modificationProstacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyQuinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyQuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine.Risk C: Monitor therapySodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced.Risk C: Monitor therapyTacrolimus (Systemic): Potassium-Sparing Diuretics may enhance the hyperkalemic effect of Tacrolimus (Systemic).Risk C: Monitor therapyTolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapyTriamterene: May enhance the hyperkalemic effect of Spironolactone. Risk X: Avoid combinationTrimethoprim: May enhance the hyperkalemic effect of Spironolactone. Risk C: Monitor therapyFood InteractionsFood increases the bioavailability of unmetabolized spironolactone by ~90% to 95%.Dietary ConsiderationsAdministration with food increases the bioavailability of spironolactone. Excessive potassium intake (eg, salt substitutes, low-salt foods, bananas, nuts) should be avoided.Reproductive ConsiderationsSpironolactone is associated with dose-dependent menstrual irregularities (AAD [Zaenglein 2016]; ES [Funder 2016]; ES [Martin 2018]; Kallistratos 2018). Some guidelines recommend use of combination oral contraception in premenopausal patients to regulate menses and prevent pregnancy (AAD [Zaenglein 2016], ES [Martin 2018]). Decreasing the dose or switching to an alternative mineralocorticoid receptor antagonist may be appropriate for some indications (AHA [Carey 2018]; ES [Funder 2016]; Kallistratos 2018).Spironolactone is associated with dose-dependent erectile dysfunction (AAD [Zaenglein 2016]; ES [Funder 2016]; ES [Martin 2018]; Kallistratos 2018). Decreasing the dose or switching to an alternative mineralocorticoid receptor antagonist may be appropriate for some indications (AHA [Carey 2018]; ES [Funder 2016]; Kallistratos 2018). The antiandrogen blocking activity of spironolactone results in decreased spontaneous erections, sperm production, and testicular volume in transgender patients undergoing feminizing therapy (ES [Hembree 2017]).Patients taking spironolactone for primary aldosteronism (PA) who are planning to become pregnant should be switched to other agents prior to conception when possible (Forestiero 2022). Patients who require use of spironolactone for the treatment of PA should use the lowest effective dose prior to a planned pregnancy, then stop treatment once their pregnancy is confirmed (Riester 2015).Patients with heart failure who are planning to become pregnant should discontinue mineralocorticoid receptor antagonists prior to conception (AHA/ACC/HFSA [Heidenreich 2022]).Pregnancy ConsiderationsSpironolactone crosses the placenta (ESC [Regitz-Zagrosek 2018]).Based on the mechanism of action and data from animal reproduction studies, in utero exposure to spironolactone during the period of embryogenesis may cause feminization of a male fetus (limited human data; Liszewski 2019). High doses late in pregnancy may be associated with intrauterine growth restriction (Riester 2015).Chronic maternal hypertension is associated with adverse events in the fetus/infant. The risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death may be increased with chronic hypertension in pregnancy. Actual risks may be related to duration and severity of maternal hypertension. The use of mineralocorticoid receptor antagonists for the treatment of hypertension in pregnancy is generally not recommended (ACOG 203 2019).The treatment of edema associated with chronic heart failure during pregnancy is similar to that of nonpregnant patients. However, the use of mineralocorticoid receptor antagonists is not recommended. Patients diagnosed after delivery can be treated according to heart failure guidelines (AHA/ACC/HFSA [Heidenreich 2022]; ESC [Bauersachs 2016]; ESC [Regitz-Zagrosek 2018]).Data specific to the treatment of primary aldosteronism (PA) in pregnancy are limited. Patients with PA should stop spironolactone before conception or during the first trimester once the pregnancy is confirmed (Riester 2015). If spironolactone is stopped and PA is not controlled, agents other than spironolactone are recommended for the adjunctive treatment of PA during pregnancy (Forestiero 2022; Sanga 2022).Case reports describe the use of potassium-sparing diuretics such as spironolactone for the adjunctive treatment of Gitleman syndrome during pregnancy (Calò 2012; Moustakakis 2012; Shahzad 2019).Monitoring ParametersBlood pressure, serum potassium, sodium, calcium (neonates) and renal function (baseline, periodically during therapy), fluid balance, bodyweight (daily: neonates, infants)Mechanism of ActionCompetes with aldosterone for receptor sites in the distal renal tubules, increasing sodium chloride and water excretion while conserving potassium and hydrogen ions; may block the effect of aldosterone on arteriolar smooth muscle as wellPharmaco*kinetics (Adult data unless noted)Note: Suspension results in 15% to 37% higher serum concentration compared to the tablet; doses of suspension >100 mg may result in higher spironolactone concentrations than expected.Duration: Tablet: 2 to 3 daysBioavailability: High-fat/-calorie meal increased the bioavailability of spironolactone ~90%.Protein binding: >90%Metabolism: Rapid and extensive; hepatic to multiple metabolites, including active metabolites canrenone, 7-alpha-spirolactone, and 6-beta-hydroxy-7-alphaHalf-life elimination:Tablet: Spironolactone: 1.4 hours; Canrenone: 16.5 hours (terminal); 7-alpha-spirolactone: 13.8 hours (terminal)Suspension: Spironolactone: 1 to 2 hours; Canrenone, 7-alpha-spirolactone, and 6-beta-hydroxy-7-alpha: 10 to 35 hours.Time to peak, serum:Tablet: 2.6 to 4.3 hours (primarily as active metabolites)Suspension: Spironolactone: 0.5 to 1.5 hours; Canrenone: 2.5 to 5 hoursExcretion: Urine (primarily as metabolites) and bile (secondary)Pharmaco*kinetics: Additional ConsiderationsHepatic function impairment: Terminal half-life is increased in patients with cirrhotic ascites.Extemporaneous Preparations5 mg/mL Oral Suspension (ASHP Standard Concentration) (ASHP 2017)A 5 mg/mL oral suspension may be made with tablets. Crush twelve 50 mg tablets in a mortar and reduce to a fine powder. Add small portions of distilled water and mix to a uniform paste; mix while adding cherry syrup to almost 120 mL; transfer to a calibrated glass bottle, rinse mortar with cherry syrup, and add quantity of cherry syrup sufficient to make 120 mL. Label "shake well" and "refrigerate." Stable for 28 days at room temperature or refrigerated (Mathur 1989).Mathur LK, Wickman A. Stability of extemporaneously compounded spironolactone suspensions. Am J Hosp Pharm. 1989;46(10):2040-2042.28169591 mg/mL Oral SuspensionA 1 mg/mL oral suspension may be made with tablets. Crush ten 25 mg tablets in a mortar and reduce to a fine powder. Add a small amount of purified water and soak for 5 minutes; add 50 mL 1.5% carboxymethylcellulose, 100 mL syrup NF, and mix to a uniform paste; mix while adding purified water in incremental proportions to almost 250 mL; transfer to a calibrated bottle, rinse mortar with purified water, and add quantity of purified water sufficient to make 250 mL. Label "shake well." Stable for 3 months at room temperature or refrigerated (Nahata 1993).Nahata MC, Morosco RS, and Hipple TF, "Stability of Spironolactone in an Extemporaneously Prepared Suspension at Two Temperatures," Ann Pharmacother. 1993, 27(10):1198-9.825168725 mg/mL Oral SuspensionA 25 mg/mL oral suspension may be made with tablets and either a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of Ora-Sweet SF and Ora-Plus. Crush one-hundred-twenty 25 mg tablets in a mortar and reduce to a fine powder. Add small portions of chosen vehicle and mix to a uniform paste; mix while adding vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Store in amber bottles; label "shake well" and "refrigerate." Stable for 60 days refrigerated (Allen 1996).Allen LV Jr and Erickson MA 3rd, "Stability of Ketoconazole, Metolazone, Metronidazole, Procainamide Hydrochloride, and Spironolactone in Extemporaneously Compounded Oral Liquids," Am J Health Syst Pharm. 1996, 53(17):2073-8.8870895Pricing: USSuspension (CaroSpir Oral)25 mg/5 mL (per mL): $4.23Tablets (Aldactone Oral)25 mg (per each): $3.1950 mg (per each): $5.60100 mg (per each): $9.38Tablets (Spironolactone Oral)25 mg (per each): $0.19 - $0.4650 mg (per each): $0.81 - $0.88100 mg (per each): $1.42 - $1.43Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalAldactin (TW);Aldacton (TR);Aldactone (AE, AT, AU, BB, BD, BE, BF, BH, BJ, BR, CH, CI, CO, CY, CZ, DE, EC, EE, ES, ET, FI, FR, GB, GH, GM, GN, GR, HK, HR, HU, ID, IE, IL, IN, IQ, IR, IS, IT, JO, KE, KR, KW, LB, LK, LR, LU, LY, MA, ML, MR, MT, MU, MW, MX, NE, NG, NO, OM, PE, PH, PK, PT, QA, RU, SA, SC, SD, SE, SG, SI, SK, SL, SN, SY, TH, TN, TZ, UG, VE, YE, ZA, ZM, ZW);Aldactone A (AR, BM, BS, BZ, CR, DO, EC, GT, GY, HN, JM, NI, PA, SR, SV, TT, UY);Aldoxol (PY);Alizar (CL);Alspiron (RO);Altone (TH);Antagerone (EG);Belactone (LK);Diulactone (PH, VN);Drimox A (AR);Epilactone (EG);Expal (AR);Finospir (PL);Huma-Spiroton (HU);Indurit (PY);Ismian (PL);Lactone (PH);Laxtone (TW);Noractone (AE, JO);Osiren (AR, AT);Osyrol (JP);Pondactone (TH);Skyton (TW);Spectone (EG);Spilac (LK);Spinolac (VN);Spiractin (AU, NZ, ZA);Spiralang (IT);Spiretic (BD);Spirix (DK, FI, NO);Spiroctan (FR, LU);Spirofar (PH);Spirola (ID);Spirolacton (ID);Spirolon (BF, BJ, CI, EC, ET, GH, GM, GN, KE, LR, MA, ML, MR, MT, MU, MW, MY, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW);Spiron (DK, HU, TW);Spirone (PE);Spironolacton-ratiopharm (LU);Spironolactone-Eurogenerics (LU);Spironolactone-Searle (LU);Spirotone (NZ, TW);Unilactone (AE, BH, CY, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE);Uractone (LU);Uractonum (SG, TR);Verospiron (BD, BG, CZ, EE, HU, LT, SK, UA);Vivitar (CR, DO, GT, HN, MX, NI, PA, SV)For country code abbreviations (show table)<800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 40-NF 35). Rockville, MD: United States Pharmacopeia Convention; 2017:83-102.2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674-694. doi:10.1111/jgs.15767 [PubMed 30693946]Agarwal R, Rossignol P, Romero A, et al. Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2019;394(10208):1540-1550. doi:10.1016/S0140-6736(19)32135-X [PubMed 31533906]Albersheim SG, Solimano AJ, Sharma AK, et al. Randomized, double-blind, controlled trial of long-term diuretic therapy for bronchopulmonary dysplasia. J Pediatr. 1989;115(4):615-620. [PubMed 2677293]Aldactone (spironolactone) [prescribing information]. New York, NY: Pfizer Inc; February 2021.Aldactone (spironolactone) [product monograph]. Kirkland, Quebec, Canada: Pfizer Canada Inc; July 2015.American College of Obstetricians and Gynecologists (ACOG). ACOG practice bulletin no. 203: chronic hypertension in pregnancy. Obstet Gynecol. 2019;133(1):e26-e50. [PubMed 30575676]Amsterdam EA, Wenger NK, Brindis RG, et al; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; American Association for Clinical Chemistry. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [published correction appears in J Am Coll Cardiol. 2014;64(24):2713-2714]. J Am Coll Cardiol. 2014;64(24):e139-e228. doi:10.1016/j.jacc.2014.09.017 [PubMed 25260718]Aronow WS, Fleg JL, Pepine CJ, et al. ACC/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus documents developed in collaboration with the American Academy of Neurology, American Geriatrics Society, American Society for Preventive Cardiology, American Society of Hypertension, American Society of Nephrology, Association of Black Cardiologists, and European Society of Hypertension. J Am Coll Cardiol. 2011;57(20):2037-2114. [PubMed 21524875]ASHP. Standardize 4 Safety Initiative Compounded Oral Liquid Version 1.01. July 2017. https://www.ashp.org/-/media/assets/pharmacy-practice/s4s/docs/s4s-ashp-oral-compound-liquids.ashx?la=en&hash=4C2E4F370B665C028981B61F6210335AD5D0D1D6.Bakris GL, Pitt B, Weir MR, et al.; AMETHYST-DN Investigators. Effect of patiromer on serum potassium level in patients with hyperkalemia and diabetic kidney disease: the AMETHYST-DN randomized clinical trial. JAMA. 2015;314(2):151-161. doi:10.1001/jama.2015.7446 [PubMed 26172895]Barbieri RL, Chang J. Management of hirsutism in premenopausal women. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 29, 2021.Barrionuevo P, Nabhan M, Altavar O, et al. Treatment options for hirsutism: a systematic review and network meta-analysis. J Clin Endocrinol Metab. 2018;103(4):1258-1264. doi:10.1210/jc.2017-02052 [PubMed 29522176]Based on expert opinion.Bauersachs J, Arrigo M, Hilfiker-Kleiner D, et al. Current management of patients with severe acute peripartum cardiomyopathy: practical guidance from the Heart Failure Association of the European Society of Cardiology Study Group on peripartum cardiomyopathy. Eur J Heart Fail. 2016;18(9):1096-1105. [PubMed 27338866]Bazoukis G, Thom*opoulos C, Tsioufis C. Effect of mineralocorticoid antagonists on blood pressure lowering: overview and meta-analysis of randomized controlled trials in hypertension. J Hypertens. 2018;36(5):987-994. doi:10.1097/HJH.0000000000001671 [PubMed 29356711]Ben Salem C, Slim R, Fathallah N, Hmouda H. Drug-induced hyperuricaemia and gout. Rheumatology (Oxford). 2017;56(5):679-688. doi:10.1093/rheumatology/kew293 [PubMed 27498351]Borlaug BA, Colucci WS. Treatment and prognosis of heart failure with preserved ejection fraction. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 10, 2022.Brook RD, Townsend RR. Treatment of resistant hypertension. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 8, 2020.Calò LA, Caielli P. Gitelman's syndrome and pregnancy: new potential pathophysiological influencing factors, therapeutic approach and materno-fetal outcome. J Matern Fetal Neonatal Med. 2012;25(8):1511-1513. doi:10.3109/14767058.2011.629254 [PubMed 21999963]Carey RM, Calhoun DA, Bakris GL, et al; American Heart Association Professional/Public Education and Publications Committee of the Council on Hypertension; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Genomic and Precision Medicine; Council on Peripheral Vascular Disease; Council on Quality of Care and Outcomes Research; and Stroke Council. Resistant hypertension: detection, evaluation, and management: a scientific statement from the American Heart Association. Hypertension. 2018;72(5):e53-e90. doi:10.1161/HYP.0000000000000084 [PubMed 30354828]Carospir (spironolactone) [prescribing information]. Farmville, NC: CMP Pharma Inc; July 2021.Charytan DM, Himmelfarb J, Ikizler TA, et al.; Hemodialysis Novel Therapies Consortium. Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): a randomized, placebo-controlled, multiple dosage trial. Kidney Int. 2019;95(4):973-982. doi:10.1016/j.kint.2018.08.034 [PubMed 30473139]Colucci WS. Secondary pharmacologic therapy in heart failure with reduced ejection fraction (HFrEF) in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 2, 2021.Deutsch MB. Guidelines for the primary and gender-affirming care of transgender and nonbinary people. Center of Excellence for Transgender Health. http://transhealth.ucsf.edu/trans?page=guidelines-home. Published June 17, 2016. Accessed January 14, 2019.De Vecchis R, Cantatrione C, Mazzei D, Barone A, Maurea N. The Impact Exerted on Clinical Outcomes of Patients With Chronic Heart Failure by Aldosterone Receptor Antagonists: A Meta-Analysis of Randomized Controlled Trials. J Clin Med Res. 2017;9(2):130-142. doi:10.14740/jocmr2851w [PubMed 28090229]Eichenwald EC, ed. Cloherty and Stark's Manual of Neonatal Care. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2017.Engelhardt B, Blalock WA, DonLevy S, Rush M, Hazinski TA. Effect of spironolactone-hydrochlorothiazide on lung function in infants with chronic bronchopulmonary dysplasia. J Pediatr. 1989;114(4 Pt 1):619-624. [PubMed 2926575]Fanaroff AA, Fanaroff JM, eds. Klaus & Fanaroff's Care of the High-Risk Neonate. 6th ed. Philadelphia, PA: Elsevier Saunders; 2013.Feinfeld DA, Carvounis CP. Fatal hyperkalemia and hyperchloremic acidosis. Association with spironolactone in the absence of renal impairment. JAMA. 1978;240(14):1516. doi:10.1001/jama.240.14.1516 [PubMed 682358]Forestiero V, Sconfienza E, Mulatero P, Monticone S. Primary aldosteronism in pregnancy. Rev Endocr Metab Disord. Published online May 10, 2022. doi:10.1007/s11154-022-09729-6 [PubMed 35536535]Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi:10.1210/jc.2015-4061 [PubMed 26934393]Gabow PA, Moore S, Schrier RW. Spironolactone-induced hyperchloremic acidosis in cirrhosis. Ann Intern Med. 1979;90(3):338-340. doi:10.7326/0003-4819-90-3-338 [PubMed 426401]Georgianos PI, Agarwal R. Pharmacotherapy of hypertension in chronic dialysis patients. Clin J Am Soc Nephrol. 2016;11(11):2062-2075. doi:10.2215/CJN.00870116 [PubMed 27797886]Giefer MJ, Murray KF, Colletti RB. Pathophysiology, diagnosis, and management of pediatric ascites. J Pediatr Gastroenterol Nutr. 2011;52(5):503-513. [PubMed 21464748]Go AS, Bauman M, King SM, et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention [published online November 15, 2013]. Hypertension. [PubMed 24243703]Goodfellow A, Alaghband-Zadeh J, Carter G, et al. Oral spironolactone improves acne vulgaris and reduces sebum excretion. Br J Dermatol. 1984;111(2):209-214. doi:10.1111/j.1365-2133.1984.tb04045.x [PubMed 6235834]Graber E. Acne vulgaris: Management of moderate to severe acne in adolescents and adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 3, 2022.Gueiros APS, Gueiros JEB, Nóbrega KT, et al. Effect of spironolactone on the progression of coronary calcification in peritoneal dialysis patients: a pilot study. J Bras Nefrol. 2019;41(3):345-355. doi:10.1590/2175-8239-jbn-2019-0009 [PubMed 31419271]Hammer F, Malzahn U, Donhauser J, et al.; MiREnDa Study Group. A randomized controlled trial of the effect of spironolactone on left ventricular mass in hemodialysis patients. Kidney Int. 2019;95(4):983-991. doi:10.1016/j.kint.2018.11.025 [PubMed 30712923]Haynes BA, Mookadam F. Male gynecomastia. Mayo Clin Proc. 2009;84(8):672. doi:10.1016/S0025-6196(11)60515-6 [PubMed 19648382]Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18):e895-e1032. doi:10.1161/CIR.0000000000001063 [PubMed 35363499]Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an Endocrine Society clinical practice guideline. Endocr Pract. 2017;23(12):1437. doi:10.4158/1934-2403-23.12.1437 [PubMed 29320642]Hoffman DJ, Gerdes JS, Abbasi S. Pulmonary function and electrolyte balance following spironolactone treatment in preterm infants with chronic lung disease: a double-blind, placebo-controlled, randomized trial. J Perinatol. 2000;20(1):41-45. [PubMed 10693099]Huang C, Noirot LA, Reichley RM, Bouselli DA, Dunagan WC, Bailey TC. Automatic detection of spironolactone - related adverse drug events. AMIA Annu Symp Proc. 2005;2005:989. [PubMed 16779276]Ito Y, Mizuno M, Suzuki Y, et al.; Nagoya Spiro Study Group. Long-term effects of spironolactone in peritoneal dialysis patients. J Am Soc Nephrol. 2014;25(5):1094-1102. doi:10.1681/ASN.2013030273 [PubMed 24335969]James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520. [PubMed 24352797]Jeunemaitre X, Chatellier G, Kreft-Jais C, et al. Efficacy and tolerance of spironolactone in essential hypertension. Am J Cardiol. 1987;60(10):820-825. doi:10.1016/0002-9149(87)91030-7 [PubMed 3661395]Juurlink DN, Mamdani MM, Lee DS, et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med. 2004;351(6):543-551. doi:10.1056/NEJMoa040135 [PubMed 15295047]Kallistratos MS, Pittaras A, Theodoulidis I, Grassos C, Poulimenos LE, Manolis AJ. Adverse effects of mineralocorticoid receptor antagonist administration. Curr Pharm Des. 2018;24(46):5537-5541. doi:10.2174/1381612825666190222144359 [PubMed 30799782]Kliegman RM, Stanton BMD, St. Geme J, Schor NF, eds. Nelson Textbook of Pediatrics. 20th ed. Philadelphia, PA: Saunders Elsevier; 2016.Levitt JI. Spironolactone therapy and amenorrhea. JAMA. 1970;211(12):2014-2015. [PubMed 5467162]Liszewski W, Boull C. Lack of evidence for feminization of males exposed to spironolactone in utero: a systematic review. J Am Acad Dermatol. 2019;80(4):1147-1148. [PubMed 30352280]Mackenzie IS, Morant SV, Wei L, Thompson AM, MacDonald TM. Spironolactone use and risk of incident cancers: a retrospective, matched cohort study. Br J Clin Pharmacol. 2017;83(3):653-663. doi:10.1111/bcp.13152 [PubMed 27735065]Maddox TM, Januzzi JL Jr, Allen LA, et al. 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021;77(6):772-810. doi:10.1016/j.jacc.2020.11.022 [PubMed 33446410]Mann JFE. Choice of drug therapy in primary (essential) hypertension. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 23, 2021.Martin KA, Anderson RR, Chang RJ, et al. Evaluation and treatment of hirsutism in premenopausal women: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(4):1233-1257. doi:10.1210/jc.2018-00241 [PubMed 29522147]Moustakakis MN, Bockorny M. Gitelman syndrome and pregnancy. Clin Kidney J. 2012;5(6):552-555. doi:10.1093/ckj/sfs126 [PubMed 26064481]Muhlemann MF, Carter GD, Cream JJ, Wise P. Oral spironolactone: an effective treatment for acne vulgaris in women. Br J Dermatol. 1986;115(2):227-232. doi:10.1111/j.1365-2133.1986.tb05722.x [PubMed 2943311]Mulatero P, Rabbia F, Milan A, Paglieri C, Morello F, Chiandussi L, Veglio F. Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism. Hypertension. 2002;40(6):897-902. [PubMed 12468576]National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Pediatrics. 2004;114(2)(suppl 4th Report):555-576. [PubMed 15286277]Nuttall FQ, Warrier RS, Gannon MC. Gynecomastia and drugs: a critical evaluation of the literature. Eur J Clin Pharmacol. 2015;71(5):569-578. doi:10.1007/s00228-015-1835-x [PubMed 25827472]O'Gara PT, Kushner FG, Ascheim DD, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(4):e362-e425. [PubMed 23247304]Oxlund CS, Henriksen JE, Tarnow L, Schousboe K, Gram J, Jacobsen IA. Low dose spironolactone reduces blood pressure in patients with resistant hypertension and type 2 diabetes mellitus: a double blind randomized clinical trial. J Hypertens. 2013;31(10):2094-2102. doi:10.1097/HJH.0b013e3283638b1a [PubMed 24107738]Park, MK. Park's Pediatric Cardiology for Practitioners. 6th ed. Philadelphia, PA: Elsevier Health Sciences; 2014.Phelps DL, Karim A. Spironolactone: relationship between concentrations of dethioacetylated metabolite in human serum and milk. J Pharm Sci. 1977;66(8):1203. [PubMed 894512]Pitt B, Pfeffer MA, Assmann SF, et al; TOPCAT Investigators. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370(15):1383-1392. doi:10.1056/NEJMoa1313731 [PubMed 24716680]Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction [published correction appears in N Engl J Med. 2003 May 29;348(22):2271]. N Engl J Med. 2003;348(14):1309-1321. doi:10.1056/NEJMoa030207 [PubMed 12668699]Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341(10):709-717. doi:10.1056/NEJM199909023411001 [PubMed 10471456]Prior JC, Vigna YM, Watson D. Spironolactone with physiological female steroids for presurgical therapy of male-to-female transsexualism. Arch Sex Behav. 1989;18(1):49-57. doi:10.1007/bf01579291 [PubMed 2540730]Prisant LM, Chin E. Gynecomastia and hypertension. J Clin Hypertens (Greenwich). 2005;7(4):245-248. doi:10.1111/j.1524-6175.2005.04105.x [PubMed 15860966]Refer to manufacturer's labeling.Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J. 2018;39(34):3165-3241. [PubMed 30165544]Riester A, Reincke M. Progress in primary aldosteronism: mineralocorticoid receptor antagonists and management of primary aldosteronism in pregnancy. Eur J Endocrinol. 2015;172(1):R23-R30. [PubMed 25163723]Rose LI, Underwood RH, Newmark SR, Kisch ES, Williams GH. Pathophysiology of spironolactone-induced gynecomastia. Ann Intern Med. 1977;87(4):398-403. doi:10.7326/0003-4819-87-4-398 [PubMed 907238]Rozner RN, Freites-Martinez A, Shapiro J, Geer EB, Goldfarb S, Lacouture ME. Safety of 5α-reductase inhibitors and spironolactone in breast cancer patients receiving endocrine therapies. Breast Cancer Res Treat. 2019;174(1):15-26. doi:10.1007/s10549-018-4996-3 [PubMed 30467659]Runyon BA. Ascites in adults with cirrhosis: Initial therapy. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 7, 2020.Runyon BA; AASLD. Introduction to the revised American Association for the Study of Liver Diseases practice guideline management of adult patients with ascites due to cirrhosis 2012. Hepatology. 2013;57(4):1651-1653. doi:10.1002/hep.26359 [PubMed 23463403]Sabatier P, Amar J, Montastruc F, et al. Breast cancer and spironolactone: an observational postmarketing study. Eur J Clin Pharmacol. 2019;75(11):1593-1598. doi:10.1007/s00228-019-02740-y [PubMed 31418056]Sabri M, Saps M, Peters JM. Pathophysiology and management of pediatric ascites. Curr Gastroenterol Rep. 2003;5(3):240-246. [PubMed 12734047]Sanga V, Rossitto G, Seccia TM, Rossi GP. Management and outcomes of primary aldosteronism in pregnancy: a systematic review. Hypertension. 2022;79(9):1912-1921. doi:10.1161/HYPERTENSIONAHA.121.18858 [PubMed 35686552]Shah KB, Rao K, Sawyer R, Gottlieb SS. The adequacy of laboratory monitoring in patients treated with spironolactone for congestive heart failure. J Am Coll Cardiol. 2005;46(5):845-849. doi:10.1016/j.jacc.2005.06.010 [PubMed 16139135]Shahzad MA, Mukhtar M, Ahmed A, Ullah W, Saeed R, Hamid M. Gitelman syndrome: a rare cause of seizure disorder and a systematic review. Case Rep Med. 2019;2019:4204907. doi:10.1155/2019/4204907 [PubMed 30867665]Shaw JC. Low-dose adjunctive spironolactone in the treatment of acne in women: a retrospective analysis of 85 consecutively treated patients. J Am Acad Dermatol. 2000;43(3):498-502. doi:10.1067/mjd.2000.105557 [PubMed 10954662]Slaughter JL, Stenger MR, Reagan PB. Variation in the use of diuretic therapy for infants with bronchopulmonary dysplasia. Pediatrics. 2013;131(4):716-723. [PubMed 23478874]Smith SC Jr, Benjamin EJ, Bonow RO, et al. AHA/ACC Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2011 Update: A Guideline From the American Heart Association and American College of Cardiology Foundation. Circulation. 2011;124(22):2458-2473. [PubMed 22052934]Spinowitz BS, Fishbane S, Pergola PE, et al.; ZS-005 Study Investigators. Sodium zirconium cyclosilicate among Individuals with hyperkalemia: a 12-month phase 3 study. Clin J Am Soc Nephrol. 2019;14(6):798-809. doi:10.2215/CJN.12651018 [PubMed 31110051]Stewart A, Brion LP, Ambrosio-Perez I. Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease. Cochrane Database Syst Rev. 2011;(9):CD001817. [PubMed 21901679]Tamirisa KP, Aaronson KD, Koelling TM. Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure. Am Heart J. 2004;148(6):971-978. doi:10.1016/j.ahj.2004.10.005 [PubMed 15632880]Thiede RM, Rastogi S, Nardone B, et al. Hyperkalemia in women with acne exposed to oral spironolactone: a retrospective study from the RADAR (Research on Adverse Drug Events and Reports) program. Int J Womens Dermatol. 2019;5(3):155-157. doi:10.1016/j.ijwd.2019.04.024 [PubMed 31360748]US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. http://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf. Updated September 2016. Accessed October 5, 2016.Vachharajani AJ, Shah JK, Paes BA. Ovarian cyst in a premature infant treated with spironolactone. Am J Perinatol. 2001;18(6):353-356. [PubMed 11607853]van der Vorst MM, Kist JE, van der Heijden AJ, Burggraaf J. Diuretics in pediatrics: current knowledge and future prospects. Paediatr Drugs. 2006;8(4):245-264. [PubMed 16898855]Vardeny O, Claggett B, Anand I, et al. Incidence, predictors, and outcomes related to hypo- and hyperkalemia in patients with severe heart failure treated with a mineralocorticoid receptor antagonist. Circ Heart Fail. 2014;7(4):573-579. doi:10.1161/CIRCHEARTFAILURE.114.001104 [PubMed 24812304]Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014;16(1):14-26. doi:10.1111/jch.12237 [PubMed 24341872]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in Hypertension. 2018;71(6):e140-e144]. Hypertension. 2018;71(6):e13-e115. doi:10.1161/HYP.0000000000000065 [PubMed 29133356]Whitling AM, Pérgola PE, Sang JL, Talbert RL. Spironolactone-induced agranulocytosis. Ann Pharmacother. 1997;31(5):582-585. doi:10.1177/106002809703100511 [PubMed 9161653]Williams B, MacDonald TM, Morant S, et al; British Hypertension Society's PATHWAY Studies Group. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015;386(10008):2059-2068. doi:10.1016/S0140-6736(15)00257-3 [PubMed 26414968]World Health Organization (WHO). Breastfeeding and maternal medication, recommendations for drugs in the eleventh WHO model list of essential drugs. 2002. https://apps.who.int/iris/handle/10665/62435Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136(6):e137-e161. doi:10.1161/CIR.0000000000000509 [PubMed 28455343]Yancy CW, Jessup M, Bozkurt B, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;128(16):e240-e327. doi:10.1161/CIR.0b013e31829e8776 [PubMed 23741058]Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Card Fail. 2017;23(8):628-651. doi:10.1016/j.cardfail.2017.04.014 [PubMed 28461259]Yemisci A, Gorgulu A, Piskin S. Effects and side-effects of spironolactone therapy in women with acne. J Eur Acad Dermatol Venereol. 2005;19(2):163-166. doi:10.1111/j.1468-3083.2005.01072.x [PubMed 15752283]Young WF Jr. Treatment of primary aldosteronism. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 10, 2020.Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945-973.e33. doi:10.1016/j.jaad.2015.12.037 [PubMed 26897386]Topic 12803 Version 419.0

CloseBictegravir, emtricitabine, and tenofovir alafenamide: Pediatric drug informationBictegravir, emtricitabine, and tenofovir alafenamide: Pediatric drug information(For additional information see "Bictegravir, emtricitabine, and tenofovir alafenamide: Drug information" and see "Bictegravir, emtricitabine, and tenofovir alafenamide: Patient drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)ALERT: US Boxed WarningPost treatment acute exacerbation of hepatitis B:Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of bictegravir/emtricitabine/tenofovir alafenamide.Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue bictegravir/emtricitabine/tenofovir alafenamide. If appropriate, anti-hepatitis B therapy may be warranted.Brand Names: USBiktarvyBrand Names: CanadaBiktarvyTherapeutic CategoryAntiretroviral, Integrase Inhibitor (Anti-HIV);Antiretroviral, Reverse Transcriptase Inhibitor, Nucleoside (Anti-HIV);Antiretroviral, Reverse Transcriptase Inhibitor, Nucleotide (Anti-HIV)Dosing: PediatricNote: Multiple tablet strengths are available and contain different amounts of each component; use caution.HIV-1 infection, treatmentHIV-1 infection, treatment: Note: Gene mutation and antiretroviral resistance patterns should be evaluated (refer to https://www.iasusa.org for more information) when necessary.Pediatric patients:Weight 14 to <25 kg: Bictegravir 30 mg/emtricitabine 120 mg/tenofovir alafenamide 15 mg per tablet: Oral: One tablet once daily. Note: In clinical trials evaluating this dose, the youngest patients were 3 years of age.Weight ≥25 kg: Bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg per tablet: Oral: One tablet once daily.Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricPediatric patients weighing ≥14 kg:CrCl ≥30 mL/minute: No dosage adjustment necessary.CrCl <30 mL/minute: Use is not recommended.End-stage renal disease on hemodialysis: There are no dosage adjustments provided in the manufacturer's labeling; however, based on data in adults with end-stage renal disease, the standard dose is recommended, with administration after hemodialysis on dialysis days.Dosing: Hepatic Impairment: PediatricPediatric patients weighing ≥14 kg:Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.Severe impairment (Child-Pugh class C): Use is not recommended (has not been studied).Dosing: Adult(For additional information see "Bictegravir, emtricitabine, and tenofovir alafenamide: Drug information")HIV-1 infection, treatmentHIV-1 infection, treatment: One tablet (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg) once daily.Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultCrCl ≥30 mL/minute: No dosage adjustment necessary.CrCl <30 mL/minute: Use is not recommended.End-stage renal disease on hemodialysis: One tablet (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg) once daily; administer after hemodialysis on dialysis days.Dosing: Hepatic Impairment: AdultMild to moderate impairment (Child-Pugh class A or B): No dosage adjustments necessary.Severe impairment (Child-Pugh class C): Use is not recommended (has not been studied).Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Tablet, Oral: Biktarvy: Bictegravir 30 mg, emtricitabine 120 mg, and tenofovir alafenamide 15 mg, Bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mgGeneric Equivalent Available: USNoDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Tablet, Oral: Biktarvy: Bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mgAdministration: PediatricOral: Administer with or without food.Bictegravir 30 mg/emtricitabine 120 mg/tenofovir alafenamide 15 mg tablet (pediatric patients weighing 14 to <25 kg): If unable to swallow tablet whole, tablet may be split and each part swallowed separately; all parts should be swallowed within ~10 minutes.Administration: AdultOral: Administer with or without food. Administer 2 hours before or 6 hours after aluminum- or magnesium-containing antacids. Administer with food with concomitant calcium- or iron-containing supplements or antacids; coadministration with or 2 hours after calcium- or iron-containing supplements or antacids is not recommended under fasting conditions.Storage/StabilityBlister pack: Store at 25°C (77°F); excursion permitted to 15°C to 30°C (59°F to 86°F); store in original blister package.Bottle: Store below 30°C (86°F); dispense in original container. Do not discard desiccant.UseTreatment of HIV-1 infection as initial therapy in those with no antiretroviral (ARV) treatment history or to replace a current stable ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) with no history of treatment failure and no known substitutions associated with resistance to the individual components (FDA approved in pediatric patients weighing ≥14 kg and adults).Adverse Reactions (Significant): ConsiderationsKidney injuryThe tenofovir alafenamide fumarate (TAF) component of bictegravir, emtricitabine, tenofovir alafenamide (BIC/FTC/TAF) is associated with kidney impairment, acute kidney injury (AKI), and proximal tubular nephropathy. Cases of TAF-associated AKI and renal tubulopathy (RT) have been reported (Ref). Syndromes reported include Fanconi syndrome (FS) (Ref), FS (Ref) and FS with nephrogenic diabetes insipidus (Ref). AKI or RT resolution occurred immediately to 3 months after discontinuation (Ref). Renal function may not return to baseline (Ref). Incidence is lower than with tenofovir disoproxil fumarate (TDF) (Ref). TAF has been used safely in patients previously diagnosed with TDF-related FS/RT (Ref).Mechanism: Dose- and time-related; tenofovir inhibition of DNA polymerase-gamma results in mitochondrial DNA (mtDNA) depletion, mitochondrial dysfunction, and cell toxicity (Ref). Proximal tubule epithelial cells are susceptible due to active uptake of tenofovir by OAT-1 and OAT-3 and efflux by MDRP-4 (Ref). Although TAF is converted to tenofovir in target lymphoid cells and hepatocytes rather than in the plasma like TDF, the proportion of the dose reaching the kidneys is similar. Proximal tubule epithelial cell exposure to tenofovir from TAF is lower than TDF (Ref).Onset: Varied; onset ranged from 1 day to 9 months, depending on associated risk factors, in reported AKI or RT cases (Ref). In some cases, patients have had prolonged prior use with TDF before initiation of TAF (Ref). AKI has been described with TDF years after TDF initiation (Ref).Risk factors:• Concurrent nephrotoxic medications (Ref)• Concurrent pharmacologic boosters (eg, cobicistat) (Ref)• Preexisting kidney disease or history of AKI (Ref)• Preexisting liver disease (eg, hepatitis C coinfection) (Ref)• HIV (especially low CD4 count) (Ref)• Diabetes (Ref)• Lower body weight (Ref)• Older age (Ref)• Previous exposure to TDF (Ref)• Genetic polymorphisms (Ref)Weight gainBictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) is associated with weight gain (Ref). Median weight gain 96 weeks after initiation in antiretroviral-naïve individuals was 3.5 kg to 3.6 kg (Ref). Median weight gain at 144 weeks was 4.1 kg to 4.4 kg (Ref). Weight gain may also plateau (Ref). Weight increases with BIC/FTC/TAF are not significantly different from those after initiation of dolutegravir (DTG) + abacavir/lamivudine (ABC/3TC) or DTG + FTC/TAF (Ref), but may be larger than weight increases with darunavir, cobicistat, emtricitabine, tenofovir alafenamide (DRV/COBI/FTC/TAF) (Ref) or efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) (Ref).Switching to an integrase strand inhibitor (INSTI)-containing regimen from EFV/FTC/TDF may be associated with greater weight gain at 18 months than switching to a protease inhibitor (PI)-based regimen or remaining on EFV/FTC/TDF (Ref). Similarly, switching from a TDF to TAF may result in weight gain (Ref). Switching virally suppressed females to ABC/DTG/3TC resulted in greater weight gain than in those remaining on TDF/FTC + nonnucleoside reverse-transcriptase inhibitor (NNRTI) at 48 weeks (Ref).INSTI-containing regimens may be associated with a greater increase in waist circumference in females (Ref) and patients of black race (Ref). Addition of or switch to an INSTI-containing regimen may be associated with increased risk of metabolic syndrome (including diabetes mellitus) in females (Ref) and an increased BMI class (Ref). INSTI-containing regimens may increase risk for obesity compared with non-INSTI-containing regimens (Ref). Some data suggest an association between weight gain and cardiovascular disease in INSTI-containing regimens (Ref).Although there is a case report of a 13 kg/m2 BMI increase reversing over 2 years with a change from elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide fumarate back to EFV/FTC/TDF (Ref), it is unclear if this is generalizable (Ref).Mechanism: Not clearly established; TAF may have less of a weight suppressive effect than other nucleos(t)ide reverse transcriptase inhibitors (NRTIs). Similarly, INSTIs such as BIC may have less of a weight suppressive effect than other anchor drugs and stimulate weight gain through effects on estrogen-mediated pathways, regulation of glucose and lipid metabolism, melanocortin stimulating system suppression, or insulin sensitivity by magnesium chelation (Ref).Onset: Delayed; weight gain and BMI increases ≥5% have been observed after 12 weeks of treatment (Ref).Risk factors:• Females (Ref)• Black or Hispanic race (Ref)• Older age (Ref)• Pre-treatment obesity (adolescents) (Ref)• Lower pre-treatment BMI (adults) (Ref)Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Also see individual agents.>10%: Hepatic: Increased serum bilirubin (17%)1% to 10%:Cardiovascular: Increased serum creatine kinase (6% to 8%)Dermatologic: Skin rash (<2%)Endocrine & metabolic: Increased LDL cholesterol (4% to 5%)Gastrointestinal: Abdominal distention (1% to 2%), abdominal pain (<2%), diarrhea (3% to 6%), dyspepsia (<2%), flatulence (<2%), increased serum amylase (3%), increased serum lipase (≤2%), nausea (3% to 6%), vomiting (<2%)Hematologic & oncologic: Decreased neutrophils (3%)Hepatic: Increased gamma-glutamyl transferase (1% to 2%), increased serum alanine aminotransferase (2% to 3%), increased serum aspartate aminotransferase (2% to 5%)Nervous system: Abnormal dreams (≤3%), depression (<2%), dizziness (2%), fatigue (2% to 3%), headache (4% to 5%), insomnia (2%), suicidal ideation (2%), suicidal tendencies (2%)Frequency not defined: Renal: Increased serum creatininePostmarketing:Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria (Sax 2017)Endocrine & metabolic: Gynecomastia (Biagi 2020), weight gain (Orkin 2020)Gastrointestinal: Pancreatitis (Simeni Njonnou 2020)Hypersensitivity: AngioedemaInfection: Reactivation of HBV (following discontinuation in coinfected HIV-1 and HBV patients)Neuromuscular & skeletal: Rhabdomyolysis (Simeni Njonnou 2020)Renal: Acute kidney injury (Ueaphongsukkit 2021), Fanconi syndrome (Bahr 2019), proximal tubular nephropathy (Ueaphongsukkit 2021), renal tubular necrosisContraindicationsCoadministration with dofetilide, rifampinCanadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to bictegravir, emtricitabine , tenofovir alafenamide, or any component of the formulation; coadministration with St John’s wortWarnings/PrecautionsConcerns related to adverse effects:• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome, resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barré syndrome, autoimmune hepatitis) later in therapy; further evaluation and treatment may be required.• Lactic acidosis/hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis, sometimes fatal, have been reported with the use of nucleoside analogs, alone or in combination with other antiretrovirals. Suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (marked transaminase elevation may/may not accompany hepatomegaly and steatosis).Disease-related concerns:• Hepatic impairment: Use with caution in hepatic impairment; see "Dosing: Hepatic Impairment" for additional information.• Renal impairment: Use with caution in renal impairment; see "Dosing: Altered Kidney Function" for additional information.Warnings: Additional Pediatric ConsiderationsEmtricitabine-associated hyperpigmentation may occur at a higher frequency in pediatric patients compared to adults (children: 32%; adults: 2% to 6%). Bictegravir may increase SCr via inhibition of tubular secretion; it does not affect glomerular filtration.Through disruption in vitamin D metabolism, decreases in bone mineral density (BMD) have been observed with tenofovir alafenamide (TAF) after 48 weeks of treatment; however, the incidence and negative impact on BMD is less than that observed with tenofovir disoproxil fumarate (TDF). Additionally, TAF is associated with less renal toxicity than TDF but equal antiviral efficacy. A higher incidence of dyslipidemia has been reported with TAF than TDF. TAF is preferred over TDF whenever possible; do not use TAF and TDF concomitantly (HHS [pediatric] 2021).Metabolism/Transport EffectsRefer to individual components.Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions programAcyclovir-Valacyclovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Acyclovir-Valacyclovir. Risk C: Monitor therapyAdefovir: May diminish the therapeutic effect of Tenofovir Products. Adefovir may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Adefovir. Risk X: Avoid combinationAminoglycosides: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Risk C: Monitor therapyAntihepaciviral Combination Products: May increase the serum concentration of Bictegravir. Risk C: Monitor therapyAtazanavir: May increase the serum concentration of Bictegravir. Risk C: Monitor therapyBetibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Betibeglogene Autotemcel.Risk X: Avoid combinationCabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib.Risk C: Monitor therapyCalcium Salts: May decrease the serum concentration of Bictegravir. Management: Bictegravir, emtricitabine, and tenofovir alafenamide can be administered with calcium salts under fed conditions, but coadministration with or 2 hours after a calcium salt is not recommended under fasting conditions. Risk D: Consider therapy modificationCarBAMazepine: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combinationCidofovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Cidofovir. Risk C: Monitor therapyCladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine.Risk X: Avoid combinationClofarabine: OCT2 Inhibitors may increase the serum concentration of Clofarabine.Risk C: Monitor therapyCobicistat: May increase the serum concentration of Tenofovir Alafenamide. Risk C: Monitor therapyCYP3A4 Inducers (Strong): May decrease the serum concentration of Bictegravir. Risk C: Monitor therapyDalfampridine: OCT2 Inhibitors may increase the serum concentration of Dalfampridine.Management: Consider alternatives to this combination. Carefully weigh the risk of seizures against the benefit of combining OCT2 inhibitors with dalfampridine. Risk D: Consider therapy modificationDofetilide: Bictegravir may increase the serum concentration of Dofetilide.Risk X: Avoid combinationElivaldogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Elivaldogene Autotemcel.Management: Avoid use of antiretroviral medications for at least one month, or for the amount of time required for elimination of the retroviral medication, prior to stem cell mobilization and until the all apheresis cycles are finished Risk X: Avoid combinationFosphenytoin-Phenytoin: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combinationGanciclovir-Valganciclovir: Tenofovir Products may increase the serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase the serum concentration of Tenofovir Products.Risk C: Monitor therapyIron Preparations: May decrease the serum concentration of Bictegravir. Management: Bictegravir, emtricitabine, and tenofovir alafenamide can be administered with iron preparations under fed conditions, but coadministration with or 2 hours after an iron preparation is not recommended under fasting conditions. Risk D: Consider therapy modificationLumacaftor and Ivacaftor: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may decrease the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Risk C: Monitor therapyMetFORMIN: MATE1/2-K Inhibitors may increase the serum concentration of MetFORMIN.Risk C: Monitor therapyMitapivat: May decrease the serum concentration of UGT1A1 Substrates. Risk C: Monitor therapyNirmatrelvir and Ritonavir: May increase the serum concentration of Tenofovir Alafenamide. Risk C: Monitor therapyNonsteroidal Anti-Inflammatory Agents: May enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose due to a potential risk of acute renal failure. Diclofenac appears to confer the most risk. Risk D: Consider therapy modificationNonsteroidal Anti-Inflammatory Agents (Topical): May enhance the nephrotoxic effect of Tenofovir Products. Risk C: Monitor therapyOrlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapyOXcarbazepine: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combinationP-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of Tenofovir Alafenamide. Management: Consider alternatives to the use of P-gp inducers with tenofovir alafenamide. If combined, monitor for reduced tenofovir alafenamide concentrations and efficacy, and for the development of resistance. Risk D: Consider therapy modificationPHENobarbital: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combinationPolyvalent Cation Containing Products: May decrease the serum concentration of Bictegravir. Management: Administer bictegravir under fasting conditions at least 2 hours before or 6 hours after polyvalent cation containing products. Coadministration of bictegravir with or 2 hours after most polyvalent cation products is not recommended. Risk D: Consider therapy modificationPrimidone: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combinationRifabutin: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combinationRifabutin: May decrease the serum concentration of Bictegravir. Risk X: Avoid combinationRifAMPin: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combinationRifAMPin: May decrease the serum concentration of Bictegravir. Risk X: Avoid combinationRifapentine: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combinationRifapentine: May decrease the serum concentration of Bictegravir. Risk X: Avoid combinationRitonavir: May increase the serum concentration of Tenofovir Alafenamide. Risk C: Monitor therapySt John's Wort: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combinationSt John's Wort: May decrease the serum concentration of Bictegravir. Risk X: Avoid combinationTipranavir: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combinationUGT1A1 Inducers: May decrease the serum concentration of Bictegravir. Risk C: Monitor therapyReproductive ConsiderationsThe Health and Human Services (HHS) perinatal HIV guidelines note data are insufficient to recommend this fixed-dose combination for patients with HIV infection who are not yet pregnant but are trying to conceive.Viral suppression sustained below the limits of detection with antiretroviral therapy (ART) and modification of therapy (if needed) is recommended in all patients with HIV infection who are planning a pregnancy. Optimization of the health of the person who will become pregnant and a discussion of the potential risks and benefits of ART during pregnancy is also recommended prior to conception. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth.Health care providers caring for couples planning a pregnancy when one or both partners are diagnosed with HIV infection may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2021).Also refer to the emtricitabine and tenofovir alafenamide monographs for additional information specific to these components.Pregnancy ConsiderationsBictegravir crosses the placenta.Data collected by the antiretroviral registry related to the use of bictegravir in pregnancy are insufficient to evaluate teratogenicity. Refer to the emtricitabine and tenofovir alafenamide monographs for additional information specific to these components.The Health and Human Services (HHS) perinatal HIV guidelines note data are insufficient to recommend this fixed-dose combination for pregnant patients with HIV infection who are antiretroviral-naive, who have had antiretroviral therapy (ART) in the past but are restarting, who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen), or who become pregnant during therapy.Pharmaco*kinetic studies of bictegravir are insufficient to make dosing recommendations for pregnant patients.ART is recommended for all pregnant people with HIV infection to maximize their health, maintain the viral load below the limit of detection, and reduce the risk of perinatal transmission. Therapy should be individualized following a discussion of the potential risks and benefits of treatment during pregnancy. Patients on fully suppressive regimens prior to pregnancy generally may continue the same regimen considering known pregnancy outcomes and pharmaco*kinetic data. Monitoring of patients who are pregnant is more frequent than in patients who are not pregnant. ART initiated during pregnancy can be modified after delivery. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth.Data collection to monitor pregnancy and infant outcomes following exposure to ART is ongoing. Health care providers are encouraged to enroll patients who are pregnant exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.APRegistry.com).Health care providers caring for pregnant patients with HIV infection and their infants may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2021).Monitoring ParametersHIV: General recommendations: Management of HIV infection requires extensive monitoring; refer to current guidelines (https://clinicalinfo.hiv.gov/en/guidelines) for additional guidance. Antiretroviral (ARV) drug-resistance testing is recommended before initiation of therapy in treatment-naive patients. After initiation of or change in ARV therapy regimen, pediatric patients should be evaluated for clinical adverse effects and treatment adherence at 1 to 2 weeks, and laboratory testing for drug toxicity should occur at 2 to 4 weeks; monitor for therapy adherence, effectiveness, and toxicities every 3 to 4 months.Drug-specific monitoring: Frequency may vary based on several factors including age, concomitant therapy, and clinical response; refer to current guidelines for additional information.Screen for hepatitis B prior to starting therapy (in patients who previously demonstrated no immunity to hepatitis B). For patients with hepatitis B coinfection, monitor hepatic function and hepatitis B viral load for several months after therapy is stopped.Serum electrolytes (including anion gap), SCr, serum phosphorus, urine protein/glucose, lipid profiles, bilirubin, creatine kinase (baseline and periodically with therapy or if clinical presentation indicates need), serum lactate (if clinical presentation indicates need).Note: Bictegravir may increase SCr via inhibition of tubular secretion; it does not affect glomerular filtration.Mechanism of ActionBictegravir, an integrase inhibitor, inhibits HIV integrase by binding to the integrase-active site and blocking the strand transfer step of DNA integration. Emtricitabine is a cytidine analogue and tenofovir alafenamide is converted intracellularly to tenofovir (adenosine nucleotide analog) and subsequently phosphorylated by cellular kinases to the active moiety, tenofovir diphosphate. Emtricitabine and tenofovir alafenamide interfere with HIV viral RNA-dependent DNA polymerase activities resulting in inhibition of viral replication.Pharmaco*kinetics (Adult data unless noted)Protein binding: Bictegravir: >99%; Emtricitabine <4%; Tenofovir alafenamide ~80%Metabolism:Bictegravir: By CYP3A enzymes and hepatic glucuronidation mediated by UGT1A1Emtricitabine: Not significantly metabolizedTenofovir alafenamide: Converted intracellulary by hydrolysis (non-CYP enzymes) to tenofovir then phosphorylated by cellular kinases to the active moiety, tenofovir diphosphate; minimal extent by CYP3AHalf-life elimination: Bictegravir: 17.3 hours; Emtricitabine: 10.4 hours; Tenofovir alafenamide: 0.51 hours (active metabolite, tenofovir diphosphate: 150 to 180 hours [intracellular])Time to peak: Bictegravir: 2 to 4 hours; Emtricitabine: 1.5 to 2 hours; Tenofovir alafenamide: 0.5 to 2 hoursExcretion: Bictegravir: Feces (60.3%), urine (35%); Emtricitabine: Feces (13.7%), urine (70%); Tenofovir alafenamide: Feces (31.7%), urine (<1%)Pharmaco*kinetics: Additional ConsiderationsPediatric: Exposures to all three components were higher in pediatric patients 3 to <12 years of age as compared to adults and trough concentrations of bictegravir were lower in pediatric patients 12 to <18 years as compared to adults; differences are not considered clinically significant.Pricing: USTablets (Biktarvy Oral)30-120-15 mg (per each): $143.3550-200-25 mg (per each): $143.35Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalBiktarvy (AR, AT, AU, CZ, DE, DK, EE, FR, GB, HR, IE, IN, IS, JP, KR, LT, LV, NL, NO, NZ, PL, PT, RO, SK, TW)For country code abbreviations (show table)Aloy B, Tazi I, Bagnis CI, et al. Is tenofovir alafenamide safer than tenofovir disoproxil fumarate for the kidneys? AIDS Rev. 2016;18(4):184-192. [PubMed 27438578]Asundi A, Olson A, Jiang W, et al. Integrase inhibitor use associated with weight gain in women and incident diabetes mellitus. AIDS Res Hum Retroviruses. 2022;38(3):208-215. doi:10.1089/AID.2021.0091 [PubMed 34877881]Bahr NC, Yarlagadda SG. Fanconi syndrome and tenofovir alafenamide: A case report. Ann Intern Med. 2019;170(11):814-815. doi:10.7326/L18-0592 [PubMed 30690644]Biagi MJ, Schriever CA, Chiampas TD, Michienzi SM, Patel MC, Young JD, Badowski ME. Development of gynecomastia following initiation of bictegravir/emtricitabine/tenofovir alafenamide. Int J STD AIDS. 2020;31(4):380-382. doi:10.1177/0956462419895665 [PubMed 32041480]Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) [prescribing information]. Foster City, CA: Gilead Sciences; October 2022.Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) [prescribing information]. Foster City, CA: Gilead Sciences; November 2022.Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) [product monograph]. Mississauga, Ontario, Canada: Gilead Sciences Canada Inc; November 2021.Cho AY, Oh JH, Moon HC, et al. A severe case of tenofovir-associated acute kidney injury requiring hemodialysis in a patient with chronic hepatitis B. Kidney Res Clin Pract. 2020;39(3):373-375. doi:10.23876/j.krcp.20.018 [PubMed 32868494]Deiva A, Jayaprakash V, Jose N, Chandan Kumar KN, Jayakumar M. Acute kidney injury in a patient treated with tenofovir alafenamide fumarate for Hepatitis B virus infection. Saudi J Kidney Dis Transpl. 2021;32(2):592-594. doi:10.4103/1319-2442.335480 [PubMed 35017362]Emond B, Rossi C, Rogers R, Lefebvre P, Lafeuille MH, Donga P. Real-world analysis of weight gain and body mass index increase among patients with HIV-1 using antiretroviral regimen containing tenofovir alafenamide, tenofovir disoproxil fumarate, or neither in the United States. J Health Econ Outcomes Res. 2022;9(1):39-49. doi:10.36469/jheor.2022.31825 [PubMed 35233432]Goldberg RN, Kania AT, Michienzi SM, Patel M, Badowski ME. Weight gain in incarcerated individuals living with HIV after switching to integrase strand inhibitor-based therapy. J Int Assoc Provid AIDS Care. 2021;20:2325958221996860. doi:10.1177/2325958221996860 [PubMed 33626965]Gomez M, Seybold U, Roider J, Härter G, Bogner JR. A retrospective analysis of weight changes in HIV-positive patients switching from a tenofovir disoproxil fumarate (TDF)- to a tenofovir alafenamide fumarate (TAF)-containing treatment regimen in one German university hospital in 2015-2017. Infection. 2019;47(1):95-102. doi:10.1007/s15010-018-1227-0. Erratum in: Infection. 2018. [PubMed 30269210]Hamzah L, Williams D, Bailey AC, et al; Fanconi-Tenofovir Alafenamide trial team. Early safety of tenofovir alafenamide in patients with a history of tubulopathy on tenofovir disoproxil fumarate: a randomized controlled clinical trial. HIV Med. 2020;21(3):198-203. doi:10.1111/hiv.12819 [PubMed 31679186]Herlitz LC, Mohan S, Stokes MB, Radhakrishnan J, D'Agati VD, Markowitz GS. Tenofovir nephrotoxicity: acute tubular necrosis with distinctive clinical, pathological, and mitochondrial abnormalities. Kidney Int. 2010;78(11):1171-1177. doi:10.1038/ki.2010.318 [PubMed 20811330]Heron JE, Bloch M, Vanguru V, Saunders J, Gracey DM. Renal proximal tubulopathy in an HIV-infected patient treated with tenofovir alafenamide and gentamicin: a case report. BMC Nephrol. 2020;21(1):339. doi:10.1186/s12882-020-01981-9 [PubMed 32787843]Hester EK, Greenlee S, Durham SH. Weight changes with integrase strand transfer inhibitor therapy in the management of HIV infection: A systematic review. Ann Pharmacother. 2022 Feb 8:10600280211073321. doi:10.1177/10600280211073321 [PubMed 35130714]Ibrahim F, Samarawickrama A, Hamzah L, et al; BESTT Trial Team. Bone mineral density, kidney function, weight gain and insulin resistance in women who switch from TDF/FTC/NNRTI to ABC/3TC/DTG. HIV Med. 2021;22(2):83-91. doi:10.1111/hiv.12961 [PubMed 32985122]Karris MY. Short communication: Resolution of tenofovir disoproxil fumarate induced fanconi syndrome with switch to tenofovir alafenamide fumarate in a HIV-1 and hepatitis B coinfected patient. AIDS Res Hum Retroviruses. 2017;33(7):718-722. doi:10.1089/AID.2016.0180 [PubMed 28403627]Kerchberger AM, Sheth AN, Angert CD, et al. Weight gain associated with integrase stand transfer inhibitor use in women. Clin Infect Dis. 2020;71(3):593-600. doi:10.1093/cid/ciz853 [PubMed 31504324]Kileel EM, Lo J, Malvestutto C, et al. Assessment of obesity and cardiometabolic status by integrase inhibitor use in REPRIEVE: A propensity-weighted analysis of a multinational primary cardiovascular prevention cohort of people with human immunodeficiency virus. Open Forum Infect Dis. 2021;8(12):ofab537. doi:10.1093/ofid/ofab537 [PubMed 34888395]Kumar P, Johnson M, Molina JM, et al; DRIVE-SHIFT Study Group. Brief report: Switching to DOR/3TC/TDF maintains HIV-1 virologic suppression through week 144 in the DRIVE-SHIFT trial. J Acquir Immune Defic Syndr. 2021;87(2):801-805. doi:10.1097/QAI.0000000000002642 [PubMed 33633036]Lake JE, Wu K, Bares SH, et al. Risk factors for weight gain following switch to integrase inhibitor-based antiretroviral therapy. Clin Infect Dis. 2020;71(9):e471-e477. doi:10.1093/cid/ciaa177 [PubMed 32099991]Max B, DeMarais P. Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide discontinuation and return to normal weight. Int J STD AIDS. 2021;32(1):92-95. doi:10.1177/0956462420964341 [PubMed 33176608]Mothobi NZ, Masters J, Marriott DJ. Fanconi syndrome due to tenofovir disoproxil fumarate reversed by switching to tenofovir alafenamide fumarate in an HIV-infected patient. Ther Adv Infect Dis. 2018;5(5):91-95. doi:10.1177/2049936118785497 [PubMed 30224952]Neesgaard B, Greenberg L, Miró JM, et al. Associations between integrase strand-transfer inhibitors and cardiovascular disease in people living with HIV: a multicentre prospective study from the RESPOND cohort consortium. Lancet HIV. 2022;9(7):e474-e485. doi:10.1016/S2352-3018(22)00094-7 [PubMed 35688166]Norwood J, Turner M, Bofill C, et al. Brief report: weight gain in persons with HIV switched from efavirenz-based to integrase strand transfer inhibitor-based regimens. J Acquir Immune Defic Syndr. 2017;76(5):527-531. doi:10.1097/QAI.0000000000001525 [PubMed 28825943]Novick TK, Choi MJ, Rosenberg AZ, McMahon BA, Fine D, Atta MG. Tenofovir alafenamide nephrotoxicity in an HIV-positive patient: A case report. Medicine (Baltimore). 2017;96(36):e8046. doi:10.1097/MD.0000000000008046 [PubMed 28885375]Orkin C, DeJesus E, Sax PE, et al; GS-US-380-1489; GS-US-380-1490 study investigators. Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, multicentre, phase 3, non-inferiority trials. Lancet HIV. 2020;7(6):e389-e400. doi:10.1016/S2352-3018(20)30099-0 [PubMed 32504574]Pencolé L, Lê MP, Bouchet-Crivat F, Duro D, Peytavin G, Mandelbrot L. Placental transfer of the integrase strand inhibitors cabotegravir and bictegravir in the ex-vivo human cotyledon perfusion model. AIDS. 2020;34(14):2145-2149. doi:10.1097/QAD.0000000000002637 [PubMed 32796211]Pilkington V, Hughes SL, Pepperrell T, McCann K, Gotham D, Pozniak AL, Hill A. Tenofovir alafenamide vs. tenofovir disoproxil fumarate: an updated meta-analysis of 14 894 patients across 14 trials. AIDS. 2020;34(15):2259-2268. doi:10.1097/QAD.0000000000002699 [PubMed 33048869]Rebeiro PF, Jenkins CA, Bian A, et al. Risk of incident diabetes mellitus, weight gain, and their relationships with integrase inhibitor-based initial antiretroviral therapy among persons with human immunodeficiency virus in the United States and Canada. Clin Infect Dis. 2021;73(7):e2234-e2242. doi:10.1093/cid/ciaa1403 [PubMed 32936919]Ruderman SA, Crane HM, Nance RM, et al. Brief report: Weight gain following ART initiation in ART-naïve people living with HIV in the current treatment era. J Acquir Immune Defic Syndr. 2021;86(3):339-343. doi:10.1097/QAI.0000000000002556 [PubMed 33148997]Sax PE, DeJesus E, Crofoot G, et al. Bictegravir versus dolutegravir, each with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection: a randomised, double-blind, phase 2 trial. Lancet HIV. 2017;4(4):e154-e160. doi:10.1016/S2352-3018(17)30016-4 [PubMed 28219610]Sax PE, Erlandson KM, Lake JE, et al. Weight gain following initiation of antiretroviral therapy: risk factors in randomized comparative clinical trials. Clin Infect Dis. 2020;71(6):1379-1389. doi:10.1093/cid/ciz999 [PubMed 31606734]Serota DP, Franch HA, Cartwright EJ. Acute kidney injury in a patient on tenofovir alafenamide fumarate after initiation of treatment for hepatitis C virus infection. Open Forum Infect Dis. 2018;5(8):ofy189. doi:10.1093/ofid/ofy189 [PubMed 30151414]Simeni Njonnou SR, Henrard S, Noure L, Goffard JC. Severe rhabdomyolysis and acute asymptomatic pancreatitis following the concomitant use of Biktarvy in the setting of hyperosmolar diabetic crisis. BMJ Case Rep. 2020;13(7):e234483. doi: 10.1136/bcr-2020-234483. [PubMed 32611654]Stellbrink HJ, Arribas JR, Stephens JL, et al. Co-formulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2019;6(6):e364-e372. doi:10.1016/S2352-3018(19)30080-3 [PubMed 31068272]Ueaphongsukkit T, Gatechompol S, Avihingsanon A, et al. Tenofovir alafenamide nephrotoxicity: a case report and literature review. AIDS Res Ther. 2021;18(1):53. doi:10.1186/s12981-021-00380-w [PubMed 34419091]US Department of Health and Human Services (HHS). Panel on Antiretroviral Guidelines for Adults and Adolescents. Updated January 20, 2022. Accessed August 29, 2022. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new-guidelinesUS Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in pediatric HIV infection. Updated April 11, 2022. Accessed August 29, 2022. https://clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/whats-new-guidelinesUS Department of Health and Human Services (HHS) Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the use of antiretroviral agents in pediatric HIV infection. Available at https://clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/whats-new-guidelines. Updated April 7, 2021. Accessed October 15, 2021.US Department of Health and Human Services (HHS) Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission. Recommendations for the use of antiretroviral drugs during pregnancy and interventions to reduce perinatal HIV transmission in the United States. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/Perinatal_GL.pdf. Updated December 30, 2021. Accessed January 3, 2022.van Wyk J, Ajana F, Bisshop F, et al. Efficacy and safety of switching to dolutegravir/lamivudine fixed-dose 2-drug regimen vs continuing a tenofovir alafenamide-based 3- or 4-drug regimen for maintenance of virologic suppression in adults living with human immunodeficiency virus type 1: Phase 3, randomized, noninferiority TANGO study. Clin Infect Dis. 2020;71(8):1920-1929. doi:10.1093/cid/ciz1243 [PubMed 31905383]Venter WDF, Moorhouse M, Sokhela S, et al. Dolutegravir plus two different prodrugs of tenofovir to treat HIV. N Engl J Med. 2019;381(9):803-815. doi:10.1056/NEJMoa1902824 [PubMed 31339677]Waheed S, Attia D, Estrella MM, et al. Proximal tubular dysfunction and kidney injury associated with tenofovir in HIV patients: a case series. Clin Kidney J. 2015;8(4):420-425. doi:10.1093/ckj/sfv041 [PubMed 26251709]Wohl DA, Yazdanpanah Y, Baumgarten A, et al. Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2019;6(6):e355-e363. doi:10.1016/S2352-3018(19)30077-3 [PubMed 31068270]Wood BR, Huhn GD. Excess weight gain with integrase inhibitors and tenofovir alafenamide: What is the mechanism and does it matter? Open Forum Infect Dis. 2021;8(12):ofab542. doi:10.1093/ofid/ofab542 [PubMed 34877366]Zhao X, Snachez CR, Gampa A, Rodby RA. Tenofovir alefanamide-induced nephrotoxicity: a rare case of fanconi syndrome and nephrogenic insipidus instigated by the "non-nephrotoxic" tenofovir-containing haart. AJKD; 2018:71(4):339.Topic 121790 Version 87.0

CloseDexamethasone (systemic): Drug informationDexamethasone (systemic): Drug information(For additional information see "Dexamethasone (systemic): Patient drug information" and see "Dexamethasone (systemic): Pediatric drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USActive Injection D [DSC];Decadron [DSC];Dexabliss;Dexamethasone Intensol;DexPak 10 Day [DSC];DexPak 13 Day [DSC];DexPak 6 Day [DSC];DoubleDex;Dxevo 11-Day;Hemady;HiDex 6-Day;MAS Care-Pak;ReadySharp Dexamethasone [DSC];TaperDex 12-Day;TaperDex 6-Day;TaperDex 7-Day;TopiDex;ZCORT 7-Day [DSC]Brand Names: CanadaAPO-Dexamethasone;Dexamethasone Omega Unidose;Dexamethasone-Omega;Odan-Dexamethasone;PMS-Dexamethasone;PMS-Dexamethasone Sod Phosphat [DSC];PRO-Dexamethasone-4 [DSC]Pharmacologic CategoryAnti-inflammatory Agent;Antiemetic;Corticosteroid, SystemicDosing: AdultNote: Dosing: Evidence to support an optimal dose and duration is lacking for most indications; recommendations provided are general guidelines only and primarily based on expert opinion. In general, glucocorticoid dosing should be individualized and the minimum effective dose/duration should be used. Hypothalamic-pituitary-adrenal (HPA) suppression: Although some patients may become hypothalamic-pituitary-adrenal (HPA) suppressed with lower doses or briefer exposure, some experts consider HPA-axis suppression likely in any adult receiving >3 mg/day (daytime dosing) or ≥0.75 mg per 24 hours (evening or night dosing) for >2 weeks or with Cushingoid appearance (Ref); do not abruptly discontinue treatment in these patients; dose tapering may be necessary (Ref).Usual dosage range:Oral, IV, IM: 4 to 20 mg/day given in a single daily dose or in 2 to 4 divided doses; High dose: 0.4 to 0.8 mg/kg/day (usually not to exceed 40 mg/day).Indication-specific dosing:Acute mountain sickness/high-altitude cerebral edemaAcute mountain sickness/high-altitude cerebral edema (off-label use):Prevention, moderate- to high-risk situations(alternative agent): Note: Use in addition to gradual ascent and start the day of ascent.Oral: 2 mg every 6 hours or 4 mg every 12 hours; may be discontinued after staying at the same elevation for 2 to 4 days or if descent is initiated. Due to adverse effects, limit duration to ≤10 days (Ref); some experts limit to ≤7 days (Ref). In situations of rapid ascent to altitudes >3,500 meters (eg, rescue or military operations), 4 mg every 6 hours may be considered (Ref).Treatment:Acute mountain sickness (moderate to severe): Note: Dexamethasone does not facilitate acclimatization; further ascent should be delayed until patient is asymptomatic off medication (Ref).Oral, IM, IV: 4 mg every 6 hours, continue until 24 hours after symptoms resolve or descent completed (not longer than 7 days total) (Ref).High-altitude cerebral edema: Oral, IM, IV: 8 mg as a single dose, followed by 4 mg every 6 hours until descent is complete and symptoms resolve (Ref).Acute respiratory distress syndrome, moderate to severeAcute respiratory distress syndrome, moderate to severe (off-label use): Note: May consider in most patients with persistent or refractory moderate to severe acute respiratory distress syndrome who are relatively early in the disease course (within 14 days) (Ref). Do not abruptly discontinue since this may cause deterioration due to inflammatory response (Ref).IV: 20 mg once daily from days 1 to 5, then 10 mg once daily from days 6 to 10 (Ref).Adrenal insufficiency, adrenal crisisAdrenal insufficiency, adrenal crisis (alternative agent): Note: Dexamethasone should only be used if hydrocortisone is unavailable. Corticosteroid therapy should be combined with adequate fluid resuscitation in patients with primary adrenal insufficiency (Ref).IV: 4 mg every 12 hours; transition to hydrocortisone as soon as possible (Ref).Adrenal insufficiency, primary chronicAdrenal insufficiency, primary chronic (alternative agent): Note: For use in patients who are unable to tolerate treatment with other glucocorticoids (hydrocortisone is preferred); risk of overreplacement may be higher with dexamethasone (Ref). Use in conjunction with fludrocortisone. Dose is based on prednisolone equivalency.Chronic maintenance dosing:Oral: Usual dosage range: 0.25 to 0.75 mg once daily (Ref).Stress dosing:Note: Patients who are unable to tolerate oral medication (eg, due to vomiting or diarrhea), are in active labor, or are under surgical stress may require parenteral corticosteroid therapy (preferably with hydrocortisone) to prevent adrenal crisis (Ref).Patients with febrile illness: Oral: Double the chronic maintenance dose until recovery for fever 38°C (100.4°F) to 39°C (102.2°F) or triple the chronic maintenance dose until recovery for fever >39°C (102.2°F), then return to baseline dose within 1 to 3 days (Ref).Minor surgical stress (eg, hernia repair, procedures with local anesthetic): Oral: Continue chronic maintenance dose (no additional supplementation needed) (Ref); may give an additional 0.75 mg (equivalent to ~20 mg hydrocortisone) postoperatively if signs or symptoms of adrenal insufficiency are present (Ref).Antiemetic regimens: Chemotherapy-associated nausea and vomiting, preventionAntiemetic regimens: Chemotherapy-associated nausea and vomiting, prevention (off-label use): Note: When dexamethasone is given with rolapitant in a prechemotherapy regimen, the oral route for both is generally used. When checkpoint inhibitor therapy is administered in combination with emetogenic chemotherapy, there is no evidence to omit dexamethasone from the prophylactic antiemetic regimen (Ref).Single-day IV chemotherapy regimens: Highly emetogenic chemotherapy (>90% risk of emesis): Cisplatin and other highly emetogenic single agents: Dexamethasone dose depends on specific neurokinin 1 (NK1) receptor antagonist: Day of chemotherapy: Administer prior to chemotherapy and in combination with an NK1 receptor antagonist, and a 5-HT3 receptor antagonist, with or without olanzapine (Ref).In combination with aprepitant, fosaprepitant, netupitant/palonosetron (NEPA), or fosnetupitant/palonosetron: Oral, IV: 12 mg.In combination with rolapitant: Oral, IV: 20 mg.If NK1 receptor antagonist not used: Oral, IV: 20 mg.Postchemotherapy days:If aprepitant given: Oral, IV: 8 mg once daily on days 2 to 4 (Ref).If fosaprepitant given: Oral, IV: 8 mg once on day 2, followed by 8 mg twice daily on days 3 and 4 (Ref).If NEPA or fosnetupitant/palonosetron given: Prophylaxis with dexamethasone on subsequent days is not needed unless regimen contained cisplatin: Oral, IV: 8 mg once daily on days 2 to 4 (Ref).If rolapitant given: Oral, IV: 8 mg twice daily on days 2 to 4 (Ref).If NK1 receptor antagonist not used: Oral, IV: 8 mg twice daily on days 2 to 4 (Ref).Highly emetogenic chemotherapy (>90% risk of emesis): Breast cancer regimens that include an anthracycline combined with cyclophosphamide:Dexamethasone dose depends on specific NK1 receptor antagonist: Day of chemotherapy: Administer prior to chemotherapy and in combination with an NK1 receptor antagonist, and a 5-HT3 receptor antagonist, with or without olanzapine (Ref).In combination with aprepitant, fosaprepitant, NEPA, fosnetupitant/palonosetron: Oral, IV: 12 mg (Ref).In combination with rolapitant: Oral, IV: 20 mg (Ref).If NK1 receptor antagonist not used: Oral, IV: 20 mg (Ref).Postchemotherapy days: Dexamethasone use is not recommended (an alternative agent or agents is/are recommended) (Ref).Moderately emetogenic chemotherapy (30% to 90% risk of emesis): Carboplatin-based regimens: Dexamethasone dose depends on specific NK1 receptor antagonist (Ref):Day of chemotherapy: Administer prior to chemotherapy and in combination with an NK1 receptor antagonist and a 5-HT3 receptor antagonist (Ref).In combination with aprepitant, fosaprepitant, NEPA, or fosnetupitant/palonosetron: Oral, IV: 12 mg (Ref).In combination with rolapitant: Oral, IV: 20 mg (Ref).Postchemotherapy days: Prophylaxis is not necessary on subsequent days (Ref).Moderately emetogenic chemotherapy (30% to 90% risk of emesis): Non-carboplatin-based regimens: Day of chemotherapy: Administer prior to chemotherapy and in combination with a 5-HT3 receptor antagonist: Oral, IV: 8 mg (Ref).Postchemotherapy days: Note: Consider single-agent dexamethasone use for regimens containing agents with known potential to induce delayed emesis (eg, oxaliplatin, cyclophosphamide, doxorubicin) (Ref); a single-day dexamethasone regimen may be employed when utilizing palonosetron (Ref); however, if a first-generation 5-HT3 antagonist was used on day 1 rather than palonosetron, some experts suggest the first-generation 5-HT3 receptor antagonist be continued for postchemotherapy emetic prophylaxis on days 2 and 3 (Ref).Oral, IV: 8 mg on days 2 and 3 (Ref).Low emetogenic risk (10% to 30% risk of emesis): Oral, IV: 4 to 8 mg administered as a single agent in a single dose prior to chemotherapy; prophylaxis is not necessary on subsequent days (Ref).Antiemetic regimens: Postoperative nausea and vomiting, preventionAntiemetic regimens: Postoperative nausea and vomiting, prevention (off-label use): Note: May be used alone or in combination with one or more other prophylactic interventions depending on risk factors (Ref).IV: 4 to 10 mg once, before or after induction of anesthesia. Dose depends on risk and type of surgery (Ref).Antiemetic regimens: Radiation therapy-associated nausea and vomiting, preventionAntiemetic regimens: Radiation therapy-associated nausea and vomiting, prevention (off-label use): High emetogenic risk radiation therapy (total body irradiation): Radiation day(s): Oral, IV: 4 mg once daily prior to each fraction of radiation; give in combination with a 5-HT3 receptor antagonist (Ref).Postradiation days: Oral, IV: The appropriate duration of therapy following radiotherapy days is not well defined; ASCO guidelines recommend continuing dexamethasone 4 mg once on the day after each day of radiation if radiation is not planned for that day (Ref).Moderate emetogenic risk radiation therapy (upper abdomen, craniospinal irradiation):Radiation day(s): Oral, IV: 4 mg once daily prior to each of the first 5 fractions of radiation; give in combination with a 5-HT3 receptor antagonist (Ref).Asthma, acute exacerbationAsthma, acute exacerbation (alternative agent) (off-label use): Note: Alternative to a longer course of other corticosteroids in mild to moderate exacerbations or in patients who do not respond promptly and completely to short-acting beta-agonists; administer within 1 hour of presentation to emergency department (Ref).Oral: 12 to 16 mg daily for 1 to 2 days only (Ref); longer treatment at this dose may be associated with metabolic adverse effects (Ref).Cancer-related cachexiaCancer-related cachexia (off-label use): Oral: 3 to 4 mg once daily; short-term therapy (weeks) is recommended, although duration of treatment depends on treatment goals and risk/benefit assessment (Ref) or 3 to 6 mg/day for up to 4 weeks (Ref).Cancer-related pain, advanced cancer, adjuvant therapyCancer-related pain, advanced cancer, adjuvant therapy (off-label use): Note: Although available data are limited and with mixed results, dexamethasone may provide clinical benefit in the management of a variety of types of pain in patients with advanced cancer (Ref). Due to the risk for potential toxicity, carefully consider the risks and benefits of glucocorticoid use for treating cancer-related pain, including the availability of other treatments, duration of treatment, other symptoms, and life expectancy.Low-dose regimen for pain and other symptoms in the context of advanced cancer and short prognosis: Oral, IV: Initial: 0.75 to 1.5 mg once or twice daily; usual effective dose range: 1 to 2 mg IV or orally twice daily (Ref).Higher-dose regimen for pain crisis that is poorly responsive to initial opioid therapy: Oral, IV: Initial: 8 to 10 mg once; if responsive, then may consider 4 mg twice daily or 8 mg once daily; use the lowest dose that maintains pain relief while other analgesic treatments are added, if indicated (Ref).Cerebral edema associated with brain tumorCerebral (vasogenic) edema associated with brain tumor: Moderate to severe symptoms (eg, lowered consciousness/brainstem dysfunction):Initial: IV: 10 mg once followed by maintenance dosing (Ref).Maintenance: IV, Oral: 4 mg every 6 hours (Ref). Note: Consider taper after 7 days of therapy; taper slowly over several weeks (Ref).Mild symptoms: IV, Oral: 4 to 8 mg/day in 1 to 4 divided doses (Ref). Note: Consider taper after 7 days of therapy; taper slowly over several weeks (Ref).COVID-19, hospitalized patientsCOVID-19, hospitalized patients (off-label use): Note: Dexamethasone is recommended for treatment of COVID-19 in hospitalized patients requiring supplemental oxygen or ventilatory support (Ref). An equivalent dose of an alternative glucocorticoid may be substituted if dexamethasone is unavailable (Ref).IV, Oral: 6 mg once daily for up to 10 days (or until discharge if sooner) as part of an appropriate combination regimen (Ref).Cushing syndrome, diagnosisCushing syndrome, diagnosis: Note: Interpretation requires evaluation of one or more of the following: serum cortisol concentration, serum dexamethasone concentration, urinary cortisol excretion, or 17-hydroxycorticosteroid excretion; consultation with a clinical endocrinologist is recommended (Ref).Initial testing:Overnight 1 mg dexamethasone suppression test: Oral: 1 mg given once between 11 PM and 12 AM (Ref).Longer low-dose dexamethasone suppression test (2 mg/day for 48 hours): Note: May be preferred in patients with depression, anxiety, obsessive-compulsive disorder, morbid obesity, alcoholism, or diabetes mellitus (Ref).Oral: 0.5 mg every 6 hours for 48 hours for a total of 8 doses; start time varies (eg, 9 AM or12 PM) (Ref).Fetal lung maturation, acceleration ofFetal lung maturation, acceleration of (maternal administration) (off-label use): Note: Generally, for patients between 24 and 34 weeks of gestation, including those with ruptured membranes or multiple gestations, who are at risk of delivering within 7 days. A single course may be appropriate in some pregnant patients beginning at 23 weeks' gestation or late preterm (between 34 0/7 weeks' and 36 6/7 weeks' gestation) who are at risk of delivering within 7 days.IM: 6 mg every 12 hours for a total of 4 doses. May repeat course in select patients (eg, patients with pregnancies up to 34 weeks' gestation at risk for delivery within 7 days and >14 days have elapsed since initial course of antenatal corticosteroids) (Ref).Immune thrombocytopeniaImmune thrombocytopenia (initial therapy): Note: Goal of therapy is to provide a safe platelet count to prevent clinically important bleeding rather than normalization of the platelet count (Ref).Oral, IV: 40 mg once daily for 4 days and then stop (no taper); may be repeated up to 3 times if inadequate response (Ref). For severe bleeding with thrombocytopenia, give in combination with other therapies (Ref).Iodinated contrast media allergic-like reaction, preventionIodinated contrast media allergic-like reaction, prevention (alternative agent): Note: Generally for patients with a prior allergic-like or unknown-type iodinated contrast reaction who will be receiving another iodinated contrast agent. Nonurgent premedication with an oral corticosteroid (eg, prednisone) is generally preferred when contrast administration is scheduled to begin in ≥12 hours; however, consider an urgent (accelerated) regimen with an IV corticosteroid for those requiring contrast in <12 hours. Efficacy of premedication regimens starting <4 to 5 hours before the use of contrast has not been demonstrated (Ref).Urgent (accelerated) regimen: IV: 7.5 mg every 4 hours until contrast medium administration in combination with diphenhydramine (Ref).Meningitis, prevention of neurologic complicationsMeningitis (bacterial), prevention of neurologic complications (off-label use): Note: Administer first dose of dexamethasone shortly before or at the same time as the first dose of antibacterials. If antibacterials have already been administered, do not administer dexamethasone. In patients with pneumococcal meningitis who receive dexamethasone, some experts recommend adding rifampin to the standard initial antibacterial regimen or adding rifampin if susceptibility tests, once available, show intermediate susceptibility (MIC ≥2 mcg/mL) to ceftriaxone and cefotaxime (Ref).Developed world (suspected or confirmed pneumococcal meningitis): IV: 0.15 mg/kg/dose or 10 mg every 6 hours for 4 days; discontinue if culture data reveal non-pneumococcal etiology (Ref).Developing world (strongly suspected or confirmed bacterial meningitis): IV: 0.4 mg/kg/dose every 12 hours for 4 days; discontinue if culture data reveal non-pneumococcal etiology; not recommended in regions with high rates of HIV infection and/or malnutrition or in cases of delayed clinical presentation (Ref).Migraine, recurrence preventionMigraine, recurrence prevention (off-label use): IM, IV: 10 to 24 mg once in combination with standard migraine abortive therapy (Ref).Multiple myelomaMultiple myeloma: Note: Multiple dexamethasone-containing regimens are available. Refer to literature/guidelines for additional details. For many regimens, dexamethasone is continued until disease progression or unacceptable toxicity. Dexamethasone total weekly dose may be split over 2 days when combination therapies are administered on successive days (refer to protocol) (Ref).Frail patients (eg, >75 years of age, BMI <18.5 kg/m2, poorly controlled diabetes, corticosteroid intolerance): When administered weekly, dexamethasone is usually reduced to 20 mg once weekly for frail patients (Ref). May consider lower initial dexamethasone doses (8 to 20 mg once weekly) in patients >75 years of age or those with comorbidities, with subsequent titration based on response/tolerance (Ref).Combination regimens that do not include a monoclonal antibody:Oral:40 mg once weekly on days 1, 8, 15, and 22 every 28 days in combination with lenalidomide (Ref), pomalidomide (Ref), ixazomib and lenalidomide (Ref), ixazomib and lenalidomide for 18 cycles (Ref), carfilzomib and lenalidomide (Ref), or bortezomib and lenalidomide (Ref) or 40 mg once weekly on days 1, 8, 15, and 22 every 28 days in cycles 1 to 9, and then 40 mg once weekly on days 1, 8, and 15 every 28 days beginning at cycle 10 (in combination with carfilzomib) (Ref).or20 mg on days 1, 8, 15, and 22 every 28 days (in combination with lenalidomide) for 9 cycles, followed by lenalidomide maintenance (Ref) or 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 every 21 days (in combination with bortezomib and lenalidomide) for 8 cycles (induction), followed by 40 mg on days 1, 8, 15, and 22 every 28 days (in combination with lenalidomide) for maintenance (Ref) or 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 every 28 days (in combination with carfilzomib) (Ref) or 20 mg on days 1 and 3 of each week (in combination with selinexor) (Ref) or 20 mg on days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 every 35 days (in combination with selinexor and bortezomib) (Ref).or40 mg once daily on days 1 to 4 and 9 to 12 every 28 days in combination with bortezomib and lenalidomide for 6 cycles followed by transplant (Ref) or 40 mg once daily on days 1 to 4, 9 to 12, and 17 to 20 every 28 days in combination with bortezomib and doxorubicin for 3 cycles as induction (Ref). Note: Some experts reserve this dosing (for 1 cycle, followed by 40 mg once weekly thereafter) for patients with an aggressive disease presentation or acute renal failure from light chain cast nephropathy (Ref).Combination regimens that include a monoclonal antibody:Oral, IV:40 mg weekly in combination with daratumumab and pomalidomide (Ref) or daratumumab/hyaluronidase and pomalidomide (Ref) or daratumumab and lenalidomide (Ref) or daratumumab/hyaluronidase and lenalidomide (Ref) or daratumumab and carfilzomib (Ref) or isatuximab and pomalidomide (Ref) or 20 mg once daily on days 1, 2, 4, 5, 8, 9, 11, and 12 every 21 days in combination with daratumumab and bortezomib (Ref) or 20 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 every 28 days in combination with isatuximab and carfilzomib (Ref). Note: In some studies, the dexamethasone dose is split over 2 days (20 mg before daratumumab and 20 mg the day after daratumumab infusion).or40 mg weekly, except on days elotuzumab is administered (administer dexamethasone 28 mg orally [8 mg orally in patients >75 years of age] plus 8 mg IV prior to elotuzumab) in combination with elotuzumab and pomalidomide (Ref) or elotuzumab and lenalidomide (Ref).Neoplastic epidural spinal cord compression, symptomaticNeoplastic epidural spinal cord compression, symptomatic: Note: As an adjunct to definitive treatment (radiotherapy or surgery), particularly in patients with neurologic deficits (Ref).IV (initial dose): 10 or 16 mg followed by oral dosing (Ref).Oral (after IV dose): 16 mg/day (usually given in 2 to 4 divided doses). Once definitive treatment is underway, taper gradually over 1 to 2 weeks until discontinuation (Ref).Tuberculosis, central nervous systemTuberculosis, central nervous system: Note: In general, steroids are indicated for patients with established or suspected tuberculous meningitis, regardless of HIV status (Ref).IV: Initial dose: 0.3 to 0.4 mg/kg/day for 2 weeks, then 0.2 mg/kg/day for week 3, then 0.1 mg/kg/day for week 4, followed by oral therapy (Ref).Oral: Starting week 5 of treatment: 4 mg/day, then taper by 1 mg of the daily dose each week; total combined IV/oral therapy duration: ~8 weeks (Ref).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultThe renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.Note: The pharmaco*kinetics and pharmacodynamics of corticosteroids in kidney impairment are not well understood (Ref). Dexamethasone half-life is decreased in patients with severe kidney impairment (Ref), potentially due to decreased protein binding (Ref); however, the clinical implications of these findings are unclear.Oral, parenteral:Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (Ref).Hemodialysis, intermittent (thrice weekly): No supplemental dose or dosage adjustment necessary (Ref).Peritoneal dialysis: No dosage adjustment necessary (Ref).CRRT: No dosage adjustment necessary (Ref).PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).Dosing: Hepatic Impairment: AdultThere are no dosage adjustments provided in the manufacturer’s labeling.Dosing: Pediatric(For additional information see "Dexamethasone (systemic): Pediatric drug information")COVID-19, treatmentCOVID-19, treatment: Very limited data available:Note: Safety and effectiveness of dexamethasone or other corticosteroids for COVID-19 treatment have not been sufficiently evaluated in pediatric patients; use is extrapolated from adult patients; use caution. Reserve use for hospitalized patients who require high-flow oxygen, noninvasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO); not routinely recommended for pediatric patients requiring low levels of oxygen support (ie, nasal canula only). Use in profoundly immunocompromised pediatric patients should be considered only on a case-by-case basis as it has not been evaluated and may be harmful. Pediatric patients with COVID-19 should be enrolled in clinical trials whenever possible (Ref).Infants, Children, and Adolescents: IV, Oral: 0.15 to 0.3 mg/kg/dose once daily for up to 10 days; maximum dose: 6 mg/dose (Ref). Note: An equivalent dose of an alternative glucocorticoid may be substituted if dexamethasone is unavailable (Ref).Acute mountain sickness/high altitude cerebral edema; treatmentAcute mountain sickness (AMS) (moderate)/high altitude cerebral edema (HACE); treatment: Limited data available: Note: Dexamethasone does not facilitate acclimatization; further ascent should be delayed until patient is asymptomatic off medication (Ref).Infants, Children, and Adolescents: Oral, IM, IV: 0.15 mg/kg/dose every 6 hours; maximum dose: 4 mg/dose (Ref).Airway edema or extubationAirway edema or extubation: Limited data available: Infants, Children, and Adolescents: Oral, IM, IV: 0.5 mg/kg/dose (maximum dose: 10 mg/dose) administered 6 to 12 hours prior to extubation then every 6 hours for 6 doses (total dexamethasone dose: 3 mg/kg) (Ref).Anti-inflammatoryAnti-inflammatory: Infants, Children, and Adolescents: Oral, IM, IV: Initial dose range: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day in divided doses every 6 to 12 hours; dose depends upon condition being treated and response of patient; dosage for infants and children should be based on disease severity and patient response; usual adult initial daily dose range: 0.75 to 9 mg/day.Asthma exacerbationAsthma exacerbation: Limited data available: Infants, Children, and Adolescents: Oral, IM, IV: 0.6 mg/kg once daily as a single dose or once daily for 2 days; maximum dose: 16 mg/dose (Ref); single dose regimens as low as 0.3 mg/kg/dose and as high as 1.7 mg/kg/dose have also been reported (Ref). Note:Duration >2 days is not recommended due to increased risk of metabolic effects (Ref).Bacterial meningitisBacterial meningitis (Haemophilus influenzae type b): Limited data available:Infants >6 weeks and Children: IV: 0.15 mg/kg/dose every 6 hours for the first 2 to 4 days of antibiotic treatment; start dexamethasone 10 to 20 minutes before or with the first dose of antibiotic; if antibiotics have already been administered, dexamethasone use has not been shown to improve patient outcome and is not recommended (Ref). Note: For pneumococcal meningitis, efficacy results are variable and use is controversial; risk and benefits should be considered prior to use (Ref).Cerebral edemaCerebral edema: Limited data available: Note: Dose, route, and duration may vary due to underlying cause of edema; tapering may be required. Infants, Children, and Adolescents: Oral, IM, IV: Loading dose: 1 to 2 mg/kg/dose as a single dose; maintenance: 1 to 2 mg/kg/day in divided doses every 4 to 6 hours; maximum daily dose: 16 mg/day (Ref).Chemotherapy-induced nausea and vomiting, preventionChemotherapy-induced nausea and vomiting, prevention: Reported regimens variable; optimal dose not established (Ref). Refer to individual protocols and emetogenic potential:Infants, Children, and Adolescents:POGO recommendations (Ref): Note: Reduce dose by 50% if administered concomitantly with aprepitant:Highly/severely emetogenic chemotherapy: Oral, IV: 6 mg/m2/dose every 6 hours.Moderately emetogenic chemotherapy: Oral, IV:BSA ≤0.6 m2: 2 mg every 12 hours.BSA >0.6 m2: 4 mg every 12 hours.Alternate dosing: Highly/severely emetogenic chemotherapy: IV: Usual: 10 mg/m2/dose once daily on days of chemotherapy; some patients may require every 12-hour dosing; usual range: 8 to 14 mg/m2/dose (Ref).Congenital adrenal hyperplasia, maintenanceCongenital adrenal hyperplasia, maintenance: Adolescents (fully grown): Oral: 0.25 to 0.5 mg once daily; use of a liquid dosage form may be preferable to allow for better dose titration (Ref). Note: For younger patients who are still growing, hydrocortisone or fludrocortisone are preferred.CroupCroup (laryngotracheobronchitis): Limited data available; dosing regimens variable:Infants and Children: Oral, IM, IV: 0.6 mg/kg once; reported maximum dose highly variable; usual maximum dose: 16 mg/dose (Ref); in trials, maximum doses of 10 to 20 mg/dose have been reported with similar efficacy findings for mild to moderate croup. The majority of reported experience in infants are those ≥3 months of age; data available in <3 months of age is very limited (Ref). In one evaluation of 22 children >2 years of age, a maximum dose of 12 mg/dose (at 0.6 mg/kg/dose) did not decrease endogenous glucocorticoid levels (Ref). A single oral dose of 0.15 mg/kg has also been shown effective in infants ≥3 months and children with mild to moderate croup (Ref).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricInfants, Children, and Adolescents: IM, IV, Oral:Kidney impairment: There are no dosage adjustments provided in the manufacturer's labeling; use with caution.Hemodialysis or peritoneal dialysis: Based on adult data, supplemental dose is not necessary (Ref).Dosing: Hepatic Impairment: PediatricInfants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling.Dosing: Older AdultRefer to adult dosing. Use cautiously in the elderly at the lowest possible dose.Dosing: Obesity: AdultThe recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.Class 1, 2 and 3 obesity (BMI ≥30 kg/m2):Oral, IV, IM:Non–weight-based dosing: No dosage adjustment necessary (Ref). Refer to adult dosing for indication-specific doses.Weight-based dosing: Use ideal body weight to avoid overdosing and subsequent toxicity (Ref). Refer to adult dosing for indication-specific doses.Rationale for recommendations: Corticosteroids are lipophilic compounds; however, the reported pharmaco*kinetic variability due to obesity is limited and inconsistent. Two small studies evaluated pharmaco*kinetic changes with oral dexamethasone in patients with obesity. One study reported lower AUC in patients with obesity compared to patients with normal weight (Ref), while another study reported a positive correlation between actual body weight and AUC (Ref). Weight-based dosing using actual body weight could lead to supratherapeutic levels (Ref).Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.[DSC] = Discontinued productConcentrate, Oral: Dexamethasone Intensol: 1 mg/mL (30 mL) [contains alcohol, usp; unflavored flavor]Elixir, Oral: Decadron: 0.5 mg/5 mL (237 mL [DSC]) [contains alcohol, usp, benzoic acid, fd&c red #40 (allura red ac dye), propylene glycol]Generic: 0.5 mg/5 mL (237 mL)Kit, Injection, as sodium phosphate: ReadySharp Dexamethasone: 10 mg/mL [DSC] [contains benzyl alcohol, sodium sulfite]TopiDex: 10 mg/mL [contains benzyl alcohol]Kit, Injection, as sodium phosphate [preservative free]: Active Injection D: 10 mg/mL [DSC]DoubleDex: 10 mg/mLMAS Care-Pak: 10 mg/mLSolution, Oral: Generic: 0.5 mg/5 mL (240 mL, 500 mL)Solution, Injection, as sodium phosphate: Generic: 4 mg/mL (1 mL); 20 mg/5 mL (5 mL); 120 mg/30 mL (30 mL); 10 mg/mL (1 mL); 100 mg/10 mL (10 mL)Solution, Injection, as sodium phosphate [preservative free]: Generic: 4 mg/mL (1 mL); 10 mg/mL (1 mL)Solution Prefilled Syringe, Injection, as sodium phosphate [preservative free]: Generic: 10 mg/mL (1 mL)Tablet, Oral: Decadron: 0.5 mg [DSC] [scored; contains fd&c yellow #5 (tartrazine), quinoline yellow (d&c yellow #10)]Decadron: 0.75 mg [DSC] [scored; contains fd&c blue #1 (brilliant blue), quinoline yellow (d&c yellow #10)]Decadron: 4 mg [DSC], 6 mg [DSC] [scored]Hemady: 20 mg [contains corn starch]Generic: 0.5 mg, 0.75 mg, 1 mg, 1.5 mg, 2 mg, 4 mg, 6 mgTablet Therapy Pack, Oral: Dexabliss: 1.5 MG (39) (39 ea)DexPak 10 Day: 1.5 mg (35 ea [DSC]) [scored; contains fd&c red #40(allura red ac)aluminum lake]DexPak 13 Day: 1.5 mg (51 ea [DSC]) [scored; contains fd&c red #40(allura red ac)aluminum lake]DexPak 6 Day: 1.5 mg (21 ea [DSC]) [scored; contains fd&c red #40(allura red ac)aluminum lake]Dxevo 11-Day: 1.5 mg (39 ea)Dxevo 11-Day: 1.5 mg (39 ea) [scored]HiDex 6-Day: 1.5 mg (21 ea) [scored; contains fd&c red #40 (allura red ac dye)]TaperDex 12-Day: 1.5 mg (49 ea) [contains fd&c red #40 (allura red ac dye)]TaperDex 6-Day: 1.5 mg (21 ea) [scored; contains fd&c red #40 (allura red ac dye)]TaperDex 6-Day: 1.5 mg (21 ea) [scored; contains fd&c red #40(allura red ac)aluminum lake]TaperDex 7-Day: 1.5 mg (27 ea) [scored; contains fd&c red #40 (allura red ac dye)]ZCORT 7-Day: 1.5 mg (25 ea [DSC]) [scored]Generic: 1.5 mg (21 ea, 35 ea, 51 ea)Generic Equivalent Available: USMay be product dependentDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Elixir, Oral: Generic: 0.5 mg/5 mL (100 ea, 100 mL)Solution, Injection, as sodium phosphate: Generic: 4 mg/mL (5 mL); 10 mg/mL (1 mL, 10 mL)Tablet, Oral: Generic: 0.5 mg, 0.75 mg, 2 mg, 4 mgAdministration: AdultOral: Administer with meals to help prevent GI upset. If appropriate, may administer antacids between meals to help prevent peptic ulcers.Oral concentrate: Use only the calibrated dropper provided. Draw dose into dropper; squeeze dropper contents into a liquid or semi-solid food (water, juice, soda or soda-like beverage, applesauce, pudding). Gently stir for a few seconds. Administer the entire mixture immediately. Do not store for future use.IV: May administer 4 mg/mL or 10 mg/mL concentration undiluted over ≥1 minute (Ref) or infuse by IVPB over 5 to 30 minutes (Ref). Rapid administration of dexamethasone may be associated with perineal irritation (especially with higher doses); consider further dilution and slower administration by IVPB to avoid perineal irritation (Ref).IM: Administer 4 mg/mL or 10 mg/mL concentration by deep IM injection.Intra-articular or soft tissue injection: Note: Dexamethasone sodium phosphate (a short-acting solution) is the only formulation available for intra-articular or soft tissue injections in the United States or Canada. Other glucocorticoids, such as triamcinolone acetonide or methylprednisolone acetate, are used more commonly for intra-articular or soft tissue injection (Ref). Refer to product-specific labeling for further details.Intra-articular: Administer into affected joint.Soft tissue: Administer into affected tissue.Intralesional injection: Note: Dexamethasone sodium phosphate (a short-acting solution) is the only formulation available for intralesional injections in the United States or Canada. Another glucocorticoid, triamcinolone acetonide, is used more commonly for intralesional injection (Ref). Refer to product-specific labeling for further details.Intralesional: Administer into affected area.Administration: PediatricOral: May administer with food or milk to decrease GI adverse effects.Parenteral: Use preservative-free dosage forms in neonates.IM: May administer 4 mg/mL or 10 mg/mL undiluted.IV: May administer as undiluted solution (4 mg/mL or 10 mg/mL) slow IV push, usually over 1 to 4 minutes; rapid administration is associated with perineal discomfort (burning, tingling) (Ref); may consider further dilution of high doses and administration by IV intermittent infusion over 15 to 30 minutes (Ref).Use: Labeled IndicationsOral, IV, or IM injection: Anti-inflammatory or immunosuppressant agent in the treatment of a variety of diseases, including those of allergic, hematologic (eg, immune thrombocytopenia), dermatologic, neoplastic (leukemias, lymphomas, and multiple myeloma), rheumatic, autoimmune, nervous system, renal, and respiratory origin; primary or secondary adrenocorticoid deficiency (not first line); management of shock, cerebral edema, and as a diagnostic agent.Intra-articular or soft tissue injection: As adjunctive therapy for short-term administration in synovitis of osteoarthritis, rheumatoid arthritis, acute and subacute bursitis, acute gouty arthritis, epicondylitis, acute nonspecific tenosynovitis, and posttraumatic osteoarthritis.Intralesional injection: Keloids; localized hypertrophic, infiltrated, inflammatory lesions of lichen planus, psoriatic plaques, granuloma annulare, and lichen simplex chronicus (neurodermatitis); discoid lupus erythematosus; necrobiosis lipoidica diabeticorum; alopecia areata; cystic tumors of an aponeurosis or tendon (ganglia).Use: Off-Label: AdultAcute mountain sickness/high-altitude cerebral edema; Acute respiratory distress syndrome, moderate to severe; Antiemetic regimens: Chemotherapy-associated nausea and vomiting, prevention; Antiemetic regimens: Postoperative nausea and vomiting, prevention; Antiemetic regimens: Radiation therapy-associated nausea and vomiting, prevention; Asthma, acute exacerbation; Cancer-related cachexia; Cancer-related pain, advanced cancer, adjuvant therapy; COVID-19, hospitalized patients; Fetal lung maturation, acceleration of; Meningitis (bacterial), prevention of neurologic complications; Migraine, recurrence preventionMedication Safety IssuesSound-alike/look-alike issues:DexAMETHasone may be confused with desoximetasone, dexmedeTOMIDine, dextroamphetamineDecadron may be confused with PercodanAdverse Reactions (Significant): ConsiderationsAdrenal suppression (tertiary adrenal insufficiency)Adrenal suppression (tertiary adrenal insufficiency) may occur with glucocorticoids, including dexamethasone, and results from inadequate stimulation of the adrenal glands (Ref). Glucocorticoid-induced adrenal insufficiency usually resolves with discontinuation of dexamethasone, but symptoms may persist for 6 to 12 months (Ref). Adrenal insufficiency may lead to adrenal crisis, a life-threatening emergency that may present like a hypotensive shock state (Ref).Mechanism: Dose- and time-related; occurs due to lack of or diminished cortisol production by the adrenal gland (Ref). Exogenous glucocorticoids produce a similar negative feedback mechanism as endogenous cortisol, causing a subsequent decrease in adrenocorticotrophic hormone (ACTH) secretion; thus, cortisol production is suppressed resulting in adrenal atrophy and subsequent insufficiency (ie, hypothalamic-pituitary-adrenal-axis [HPA-axis] suppression) (Ref). In times of stress (eg, critical illness, trauma, surgery), the body requires stress doses in patients taking dexamethasone chronically (Ref). Primary adrenal insufficiency can be caused by dexamethasone alone (without fludrocortisone) because of its lack of mineralocorticoid activity (Ref).Onset: Varied; acute (minutes after administration) and/or chronic (2 to 20 hours to days) (Ref). Chronic dexamethasone use does not allow for the HPA axis to recover quickly (Ref).Risk factors: • High doses for prolonged periods: Although some patients may become HPA suppressed with lower doses or briefer exposure, some experts consider HPA axis-suppression likely in any adult receiving a dose comparable to prednisone >20 mg/day (daytime dosing) or a dose comparable to prednisone ≥5 mg per 24 hours (evening or night dosing) for >3 weeks or with cushingoid appearance (Ref)• Potency of glucocorticoids (Ref); dexamethasone is the most potent glucocorticoid for suppressing the HPA axis (Ref).• Abrupt withdrawal (Ref)• Concurrent interacting medications (eg, carbamazepine, St John's wort, mitotane, rifampicin, itraconazole, diltiazem, thyroid replacement therapy) (Ref)• History of previous adrenal crisis (Ref)• Use of glucocorticoid therapy delivered by various routes of administration (oral and inhaled greater risk than topical or intra-articular) (Ref)CNS and psychiatric/behavioral effectsGlucocorticoids, including dexamethasone, may cause a myriad of CNS and psychiatric/behavioral adverse reactions (Ref). Patients may develop apathy or depression. More commonly, patients develop excitatory psychiatric disturbances (including agitation, anxiety, distractibility, fear, hypomania, insomnia, irritability, lethargy, labile mood, mania, pressured speech, restlessness, and tearfulness) (Ref). Exact incidences are unclear but range from 1.8% to 57% (Ref). Severe psychiatric effects have been reported in 6% of adults receiving high-dose regimens, while depression or mania have been reported in 36% (Ref). Discontinuation or dose reductions generally resolve symptoms over days to weeks (Ref).Mechanism: Dose-related; not clearly established. Dexamethasone and other glucocorticoids may alter feedback on the hypothalamic-pituitary-adrenal axis, which may lead to mood changes (Ref). Glucocorticoids may induce glutamate release, which may be responsible for neuronal toxicity (Ref). Exogenous glucocorticoids may also impact GABAergic steroids (Ref).Onset: Varied; most cases occur early in treatment (within the first 5 days), average of 11.5 days. The majority develop within 6 weeks of initiation (Ref).Risk factors:• Higher doses (comparable to ≥80 mg prednisone) (Ref)Possible additional risk factors:• Age >30 years (Ref)• Females (Ref)• History of neuropsychiatric disorders (Ref)Cushingoid features/Cushing syndromeGlucocorticoids may cause a cushingoid appearance (truncal obesity, facial adipose tissue, dorsocervical adipose tissue), which are adverse reactions related to patient's physical features (Ref). Reactions are more metabolic than weight gain, which is related to fluid retention (edema) (Ref). Iatrogenic Cushing syndrome resulting from glucocorticoid therapy increases morbidity and mortality and decreases quality of life (Ref).Mechanism: Dose- and time-related; excess cortisol from exogenous source (dexamethasone) results in suppression of adrenocorticotrophic hormone (ACTH), commonly called iatrogenic Cushing syndrome (Ref).Onset: Delayed; may develop within the first 2 months of dexamethasone therapy, with the risk dependent on the dose and duration of treatment (Ref).Risk factors:• Higher doses (Ref)• Longer duration of use (Ref)• Drug interactions prolonging the half-life of glucocorticoids via cytochrome P450 (Ref)• BMI (high) (Ref)• Daily caloric intake (>30 kcal/kg/day) (Ref)GI effectsGlucocorticoids, including dexamethasone, may cause GI effects, including peptic ulcer (with possible perforation and hemorrhage), dyspepsia, gastritis, abdominal distention, and ulcerative esophagitis (Ref). Meta-analyses suggest that glucocorticoid monotherapy carries little to no risk of peptic ulcer disease in the general population (Ref). Studies have demonstrated an increased risk of focal small bowel perforation in infants with low birth weight receiving dexamethasone (Ref).Mechanism: Dose-related; glucocorticoids inhibit gastroprotective prostaglandin synthesis and reduce gastric mucus and bicarbonate secretion (Ref). Glucocorticoid immunosuppressive effects may prevent wound healing as well as mask GI signs and symptoms (Ref). Focal small bowel perforation is thought to be due to segmental degeneration of the muscularis externa (Ref).Risk factors:• Higher doses (equivalent to methylprednisolone ≥4 mg/day) (Ref)• Concurrent aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) (Ref)• Hospitalized (but not ambulatory) patients (Ref)• Infants with low birth weight (Ref)• Recent glucocorticoid users (7 to 28 days) versus remote or nonusers (Ref)HyperglycemiaGlucocorticoids, including dexamethasone, may provoke new-onset hyperglycemia in patients without a history of diabetes and may cause an exacerbation of diabetes mellitus (Ref). Glucose levels have been noted to increase 68% above baseline (Ref). Certain patient populations (eg, transplant, cancer, chronic rheumatologic conditions) are at particular risk due to medication combinations (Ref). Resolution may occur within 24 to 36 hours after dexamethasone discontinuation (Ref).Mechanism: Dose- and time-related; increased insulin resistance (Ref). May also interfere with insulin signaling by direct effects on the insulin receptor and the glucose transporter and may promote gluconeogenesis via liver stimulation (Ref).Onset: Rapid; 4 hours (Ref). Rapid onset of steroid-induced hyperglycemia occurred within 2 days after initiation of glucocorticoids with a peak in the late afternoon following daily dosing in the morning (Ref).Risk factors:• Dose and type of glucocorticoid (Ref)• Duration of use (Ref)• Divided versus once-daily dosing (Ref)• IV and oral routes of administration (Ref)• Older age (Ref)• Males (Ref)• BMI >25 kg/m2 (Ref)• African American or Hispanic (Ref)• eGFR <40 mL/minute/1.73 m2 (Ref)• HbA1c ≥6% (Ref)• History of gestational diabetes (Ref)• Family history of diabetes mellitus (Ref)• Concurrent use of mycophenolate mofetil and calcineurin inhibitors (Ref)• Previous history of impaired fasting glucose or impaired glucose tolerance (Ref)• Patients receiving palliative care (Ref)InfectionGlucocorticoids, including dexamethasone, have immunosuppressive and anti-inflammatory effects that are reversible with discontinuation. Infection may occur after prolonged use, including Pneumocystis jirovecii pneumonia (PJP), herpes zoster, tuberculosis, and other more common bacterial infections (Ref).Mechanism: Dose- and time-related; related to pharmacologic action (ie, multiple activities on cell macrophage production and differentiation, inhibition of T-cell activation, and effects on dendritic cells) (Ref).Onset: Varied; in one study, the median duration of glucocorticoid use prior to PJP diagnosis was 12 weeks but also occurred earlier or later in some cases (Ref).Risk factors:• Higher dose and longer duration of glucocorticoid (Ref); however, may also increase risk at lower doses (eg, ≤5 mg/day of prednisone or equivalent) (Ref).• Immunocompromised state (Ref)• Concurrent medications (immunosuppressive) (Ref)• Rheumatoid arthritis (Ref)• Interstitial lung disease (Ref)• Older adults (Ref)• Male (Ref)• Low performance status (Ref)Neuromuscular and skeletal effectsGlucocorticoid (including dexamethasone)-induced neuromuscular and skeletal effects can take the form of various pathologies in patients ranging from osteoporosis and vertebral compression fracture to myopathy to osteonecrosis in adult and pediatric patients (Ref). Glucocorticoid use is the most common cause of secondary osteoporosis; may be underrecognized and undertreated due to underestimation of risk in this patient population (Ref). Vertebral fractures are the most common glucocorticoid-related fracture (Ref). Myopathies can also occur secondary to direct skeletal muscle catabolism (Ref). Acute steroid myopathy is rare (Ref).Mechanism: Dose- and time-related; glucocorticoids have direct/indirect effects on bone remodeling with osteoblast recruitment decreasing and apoptosis increasing (Ref). Myopathies or myasthenia result from reductions in protein synthesis and protein catabolism, which can manifest as proximal muscle weakness and atrophy in the upper and lower extremities (Ref).Onset: Delayed; vertebral fracture risk is increased within 3 months of initiation and peaks at 12 months (Ref).Risk factors:Drug-related risks:• Cumulative dose of glucocorticoids prednisone >5 g or equivalent (Ref)• Children receiving ≥4 courses of glucocorticoids (Ref)• Prednisone ≥2.5 mg to 7.5 mg daily or equivalent for ≥3 months (Ref)• Myopathy may occur at prednisone doses ≥10 mg daily or equivalent, with higher doses potentiating more of a rapid onset (Ref)• Fluorinated glucocorticoid preparations (eg, dexamethasone, betamethasone, triamcinolone) have a higher risk of myopathies (Ref)General fracture risks:• Age >55 years (Ref)• BMI <18.5 kg/m2 (Ref)• Bone mineral T score below -1.5 (Ref)• Endocrine disorders (eg, hypogonadism, hyper- or hypoparathyroidism) (Ref)• Excess alcohol use (>2 units/day) (Ref)• Females (Ref)• History of falls (Ref)• Malabsorption (Ref)• Menopause and duration of menopause (Ref)• White race (Ref)• Patients with cancer (Ref)• Previous fracture (Ref)• Smoking (Ref)• Underlying inflammatory condition in all ages (eg, inflammatory bowel disease, rheumatoid arthritis) (Ref)Ocular effectsGlucocorticoid (including dexamethasone)-induced ocular effects may include increased intraocular pressure (IOP), glaucoma (open-angle), and subcapsular posterior cataract in adult and pediatric patients (Ref). Cataracts may persist after discontinuation of glucocorticoid therapy (Ref).Mechanism: Dose- and time-related; Glucocorticoids can induce cataracts by covalently bonding to lens proteins, causing destabilization of the protein structure, and oxidative changes leading to cataracts formation (Ref). There are various proposed mechanisms of IOP contributing to glaucoma, including accumulation of polymerized glycosaminoglycans in the trabecular meshwork, producing edema and increasing outflow resistance (Ref). Another mechanism may include inhibition of phagocytic endothelial cells, leading to accumulation of aqueous debris (Ref). Glucocorticoids can also alter the trabecular meshwork causing an increase in nuclear size and DNA content (Ref). In addition, they can decrease the synthesis of prostaglandins which regulate the aqueous outflow (Ref).Onset: Delayed; cataracts may occur at least 1 year after initiation of chronic glucocorticoid therapy (Ref). IOP may occur at 4 years or more after initiation (Ref).Risk factors:• Dose (Ref)• Topical > Systemic (Ref)• Duration of use in all ages (Ref)• Family history of open-angle glaucoma (Ref)• Type I diabetes mellitus (Ref)• High myopia (Ref)• Pseudophakia (Ref)• Prior vitrectomies (Ref)• Connective tissue disease and sex (eg, rheumatoid arthritis in males) (Ref)• Older patients or age <6 years (Ref)• Genetics (Ref)• Angle recessive glaucoma (Ref)Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Some reactions listed are based on reports for other agents in this same pharmacologic class and may not be specifically reported for dexamethasone.Frequency not defined:Cardiovascular: Bradycardia, cardiac arrhythmia, cardiomegaly, circulatory shock, edema, embolism (fat), heart failure (in susceptible patients), hypertension, myocardial rupture (after recent myocardial infarction), syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitisDermatologic: Acne vulgaris, allergic dermatitis, alopecia, atrophic striae, diaphoresis, ecchymoses, erythema of skin, facial erythema, fragile skin, hyperpigmentation, hypertrichosis, hypopigmentation, inadvertent suppression of skin test reaction, perianal skin irritation (itching, burning, tingling; following rapid IV injection; more common in females, with higher doses; sudden onset with resolution in <1 minute) (Allan 1986; Neff 2002; Perron 2003; Singh 2011), skin atrophy, skin rash, subcutaneous atrophy, urticaria, xerodermaEndocrine & metabolic: Decreased serum potassium, fluid retention, growth suppression (children), hirsutism, hypokalemic alkalosis, menstrual disease, negative nitrogen balance (due to protein catabolism), sodium retention, weight gainGastrointestinal: Hiccups, increased appetite, nausea, pancreatitis, pruritus ani (following IV injection)Genitourinary: Defective spermatogenesis (increased or decreased), glycosuriaHematologic & oncologic: Kaposi sarcoma (Goedert 2002), petechiaHepatic: Hepatomegaly, increased serum transaminasesHypersensitivity: Anaphylaxis, angioedema, nonimmune anaphylaxisInfection: Sterile abscessLocal: Postinjection flare (intra-articular use)Nervous system: Amyotrophy, emotional lability, euphoria, headache, increased intracranial pressure, intracranial hypertension (idiopathic; usually following discontinuation), malaise, myasthenia, neuritis, neuropathy, paresthesia, personality changes, seizure, vertigoNeuromuscular & skeletal: Charcot arthropathy, rupture of tendonOphthalmic: ExophthalmosRespiratory: Pulmonary edemaMiscellaneous: Wound healing impairmentPostmarketing:Cardiovascular: Hypertrophic cardiomyopathy (premature infants) (Kale 2015)Endocrine & metabolic: Adrenal suppression (tertiary) (Dineen 2019), Cushing syndrome (iatrogenic) (Hopkins 2005), cushingoid appearance (Hopkins 2005), exacerbation of diabetes mellitus (Tamez-Pérez 2015), hyperglycemia (Tamez-Pérez 2015), impaired glucose tolerance (Tamez-Pérez 2015), moon face (Hopkins 2005), redistribution of body fat (Hopkins 2005)Gastrointestinal: Abdominal distention (Liu 2013), intestinal perforation (Gordon 1999, Gordon 2001), peptic ulcer (with possible perforation and hemorrhage) (Liu 2013), ulcerative esophagitis (Liu 2013)Hematologic & oncologic: Tumor lysis syndrome (Chanimov 2006)Infection: Infection (Youssef 2016)Nervous system: Apathy (Ciriaco 2013, Warrington 2006), depression (Ciriaco 2013, Warrington 2006), psychiatric disturbance (including agitation, anxiety, distractibility, euphoria, fear, hypomania, insomnia, irritability, labile mood, lethargy, pressured speech, restlessness, tearfulness) (Ciriaco 2013, Warrington 2006)Neuromuscular & skeletal: Bone fracture (Buckley 2018), myopathy (Liu 2013), osteonecrosis (femoral and humoral heads) (Liu 2013), osteoporosis (Buckley 2018), steroid myopathy (Haran 2018), vertebral compression fracture (Buckley 2018)Ophthalmic: Glaucoma (Phulke 2017), increased intraocular pressure (Phulke 2017), subcapsular posterior cataract (Urban 1986)ContraindicationsHypersensitivity to dexamethasone or any component of the formulation; systemic fungal infectionsDocumentation of allergenic cross-reactivity for corticosteroids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.Warnings/PrecautionsConcerns related to adverse effects:• Adrenal suppression: May cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal axis, particularly in younger children.Disease-related concerns:• Adrenal insufficiency: Dexamethasone does not provide any mineralocorticoid activity in adrenal insufficiency (may be employed as a single dose while cortisol assays are performed). Hydrocortisone is the preferred treatment of chronic primary adrenal insufficiency and adrenal crisis (ES [Bornstein 2016]).• Cardiovascular disease: Use with caution in patients with heart failure and/or hypertension; use has been associated with fluid retention, electrolyte disturbances, and hypertension. Monitor BP. Use with caution following acute myocardial infarction; corticosteroids have been associated with myocardial rupture.• GI disease: Use with caution in patients with GI diseases (diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer, ulcerative colitis, abscess, or other pyogenic infection) due to GI perforation risk. Signs of GI perforation may be masked in patients receiving corticosteroid therapy.• Head injury: Increased mortality was observed in patients receiving high-dose IV methylprednisolone. High-dose corticosteroids should not be used for the management of head injury (BTF [Carney 2016]).• Hepatic impairment: Use with caution in patients with hepatic impairment, including cirrhosis; long-term use has been associated with fluid retention.• Hepatitis B: Reactivation may occur.• Myasthenia gravis: Use may cause transient worsening of myasthenia gravis (MG) (eg, within first 2 weeks of treatment); monitor for worsening MG (AAN [Narayanaswami 2021]).• Ocular disease: Use with caution in patients with a history of ocular herpes simplex; corneal perforation has occurred; do not use in active ocular herpes simplex. Not recommended for the treatment of optic neuritis; may increase frequency of new episodes.• Pheochromocytoma: Pheochromocytoma crisis (may be fatal) has been reported after administration of systemic corticosteroids. Consider the risk of pheochromocytoma crisis in patients with suspected or confirmed pheochromocytoma.• Renal impairment: Use with caution in patients with renal impairment; fluid retention may occur.• Seizure disorders: Use corticosteroids with caution in patients with a history of seizure disorder; seizures have been reported with adrenal crisis.• Systemic sclerosis: Use with caution in patients with systemic sclerosis; an increase in scleroderma renal crisis incidence has been observed with corticosteroid use. Monitor BP and renal function in patients with systemic sclerosis treated with corticosteroids (EULAR [Kowal-Bielecka 2017]).• Thyroid disease: Changes in thyroid status may necessitate dosage adjustments; metabolic clearance of corticosteroids increases in hyperthyroid patients and decreases in hypothyroid patients.Concurrent drug therapy issues:• Immunizations: Avoid administration of live or live attenuated vaccines in patients receiving immunosuppressive doses of corticosteroids. Non-live or inactivated vaccines may be administered, although the response cannot be predicted.Special populations:• Older adult: Use with caution in elderly patients with the smallest possible effective dose for the shortest duration.• Pediatric: May affect growth velocity; growth should be routinely monitored in pediatric patients.Dosage form specific issues:• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP ["Inactive" 1997]; Zar 2007).• Sulfite: Some products may contain sodium sulfite, a sulfite that may cause allergic-type reactions including anaphylaxis and life-threatening or less severe asthmatic episodes in susceptible patients.Other warnings/precautions:• Discontinuation of therapy: Withdraw therapy with gradual tapering of dose.• Epidural injection: Corticosteroids are not approved for epidural injection. Serious neurologic events (eg, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, stroke), some resulting in death, have been reported with epidural injection of corticosteroids, with and without use of fluoroscopy.• Intra-articular injection: May produce systemic as well as local effects. Appropriate examination of any joint fluid present is necessary to exclude a septic process. Avoid injection into an infected site. Do not inject into unstable joints. Patients should not overuse joints in which symptomatic benefit has been obtained as long as the inflammatory process remains active. Frequent intra-articular injection may result in damage to joint tissues.Warnings: Additional Pediatric ConsiderationsIn premature neonates, the use of high-dose dexamethasone (approximately >0.5 mg/kg/day) for the prevention or treatment of bronchopulmonary dysplasia has been associated with adverse neurodevelopmental outcomes, including higher rates of cerebral palsy without additional clinical benefit over lower doses; current data do not support use of high doses; further studies are needed (Watterberg 2010).Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities, which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults, including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).Metabolism/Transport EffectsSubstrate of CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP3A4 (weak)Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Abrocitinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Abrocitinib.Management: The use of abrocitinib in combination with other immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive. Risk D: Consider therapy modificationAcetylcholinesterase Inhibitors: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur.Risk C: Monitor therapyAldesleukin: Corticosteroids may diminish the antineoplastic effect of Aldesleukin.Risk X: Avoid combinationAmphotericin B: Corticosteroids (Systemic) may enhance the hypokalemic effect of Amphotericin B.Risk C: Monitor therapyAndrogens: Corticosteroids (Systemic) may enhance the fluid-retaining effect of Androgens.Risk C: Monitor therapyAntacids: May decrease the bioavailability of Corticosteroids (Oral). Management: Consider separating doses by 2 or more hours. Budesonide enteric coated tablets could dissolve prematurely if given with drugs that lower gastric acid, with unknown impact on budesonide therapeutic effects. Risk D: Consider therapy modificationAntidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.Risk C: Monitor therapyAprepitant: May increase the serum concentration of DexAMETHasone (Systemic). Management: Reduce dexamethasone dose 50% with aprepitant. Aprepitant labeling incorporates this recommendation into the dose provided for dexamethasone; further reduction is not necessary. No dose adjustment may be needed with single, low-dose aprepitant for PONV. Risk D: Consider therapy modificationBaricitinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Baricitinib.Management: The use of baricitinib in combination with potent immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive. Risk D: Consider therapy modificationBCG Products: Corticosteroids (Systemic) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of BCG Products.Risk X: Avoid combinationBile Acid Sequestrants: May decrease the absorption of Corticosteroids (Oral). Risk C: Monitor therapyBrincidofovir: Corticosteroids (Systemic) may diminish the therapeutic effect of Brincidofovir.Risk C: Monitor therapyCalcitriol (Systemic): Corticosteroids (Systemic) may diminish the therapeutic effect of Calcitriol (Systemic).Risk C: Monitor therapyCAR-T Cell Immunotherapy: Corticosteroids (Systemic) may enhance the adverse/toxic effect of CAR-T Cell Immunotherapy. Specifically, the severity and duration of neurologic toxicities may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of CAR-T Cell Immunotherapy.Management: Avoid use of corticosteroids as premedication before treatment with CAR-T cell immunotherapy agents. Corticosteroids are indicated and may be required for treatment of toxicities such as cytokine release syndrome or neurologic toxicity. Risk D: Consider therapy modificationCaspofungin: Inducers of Drug Clearance may decrease the serum concentration of Caspofungin.Management: Consider using an increased caspofungin dose of 70 mg daily in adults (or 70 mg/m2, up to a maximum of 70 mg, daily in pediatric patients) when coadministered with known inducers of drug clearance. Risk D: Consider therapy modificationCladribine: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Cladribine.Risk X: Avoid combinationClofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapyCloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine.Risk C: Monitor therapyCobicistat: May increase the serum concentration of DexAMETHasone (Systemic). Dexamethasone (Systemic) may also counteract the boosting effects of Cobicistat on some agents. DexAMETHasone (Systemic) may increase the serum concentration of Cobicistat. Management: Consider an alternative corticosteroid. Monitor patients receiving this combination closely for evidence of diminished response to the antiviral regimen. Risk D: Consider therapy modificationCoccidioides immitis Skin Test: Corticosteroids (Systemic) may diminish the diagnostic effect of Coccidioides immitis Skin Test.Management: Consider discontinuing systemic corticosteroids (dosed at 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks) several weeks prior to coccidioides immitis skin antigen testing. Risk D: Consider therapy modificationCorticorelin: Corticosteroids (Systemic) may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy.Risk C: Monitor therapyCosyntropin: Corticosteroids (Systemic) may diminish the diagnostic effect of Cosyntropin.Risk C: Monitor therapyCOVID-19 Vaccine (Adenovirus Vector): Corticosteroids (Systemic) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector).Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters) Risk D: Consider therapy modificationCOVID-19 Vaccine (Inactivated Virus): Corticosteroids (Systemic) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus).Risk C: Monitor therapyCOVID-19 Vaccine (mRNA): Corticosteroids (Systemic) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA).Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modificationCOVID-19 Vaccine (Subunit): Corticosteroids (Systemic) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit).Risk C: Monitor therapyCOVID-19 Vaccine (Virus-like Particles): Corticosteroids (Systemic) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles).Risk C: Monitor therapyCYP3A4 Inducers (Moderate): May decrease the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapyCYP3A4 Inducers (Strong): May decrease the serum concentration of DexAMETHasone (Systemic). Management: Consider dexamethasone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced dexamethasone efficacy. Consider avoiding this combination when treating life threatening conditions (ie, multiple myeloma). Risk D: Consider therapy modificationCYP3A4 Inhibitors (Moderate): May increase the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapyCYP3A4 Inhibitors (Strong): May increase the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapyDeferasirox: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased.Risk C: Monitor therapyDelavirdine: DexAMETHasone (Systemic) may decrease the serum concentration of Delavirdine.Risk C: Monitor therapyDengue Tetravalent Vaccine (Live): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live).Risk X: Avoid combinationDenosumab: May enhance the immunosuppressive effect of Corticosteroids (Systemic). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and systemic corticosteroids. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modificationDesirudin: Corticosteroids (Systemic) may enhance the anticoagulant effect of Desirudin. More specifically, corticosteroids may increase hemorrhagic risk during desirudin treatment.Management: Discontinue treatment with systemic corticosteroids prior to desirudin initiation.If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Risk D: Consider therapy modificationDesmopressin: Corticosteroids (Systemic) may enhance the hyponatremic effect of Desmopressin.Risk X: Avoid combinationDeucravacitinib: May enhance the immunosuppressive effect of Corticosteroids (Systemic). Management: The use of deucravacitinib in combination with potent immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive. Risk D: Consider therapy modificationDisulfiram: May enhance the adverse/toxic effect of Products Containing Ethanol. Management: Do not use disulfiram with dosage forms that contain ethanol. Risk X: Avoid combinationElvitegravir: DexAMETHasone (Systemic) may decrease the serum concentration of Elvitegravir.Management: Consider using an alternative corticosteroid.Monitor patients receiving these agents in combination for diminished antiviral response. Risk D: Consider therapy modificationEPHEDrine (Systemic): May decrease the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapyEstrogen Derivatives: May increase the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapyFexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combinationFilgotinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Filgotinib.Management: Coadministration of filgotinib with systemic corticosteroids at doses equivalent to greater than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks is not recommended. Risk D: Consider therapy modificationFosamprenavir: DexAMETHasone (Systemic) may decrease the serum concentration of Fosamprenavir. Fosamprenavir may increase the serum concentration of DexAMETHasone (Systemic).Risk C: Monitor therapyFosaprepitant: May increase the serum concentration of DexAMETHasone (Systemic). Management: Reduce the dexamethasone dose 50% when coadministered with aprepitant. Aprepitant prescribing information incorporates this recommendation into the dose provided for dexamethasone; further reduction is not necessary. Risk D: Consider therapy modificationFosnetupitant: May increase the serum concentration of DexAMETHasone (Systemic). Management: Decrease dexamethasone doses to 12 mg on day 1, and if needed based on the emetic potential of the regimen, 8 mg daily on days 2 to 4 of chemotherapy when administered with fosnetupitant. Risk D: Consider therapy modificationFosphenytoin: May decrease the serum concentration of DexAMETHasone (Systemic). DexAMETHasone (Systemic) may decrease the serum concentration of Fosphenytoin. DexAMETHasone (Systemic) may increase the serum concentration of Fosphenytoin. Management: Consider dexamethasone dose increases when combined with fosphenytoin and monitor closely for reduced steroid efficacy. Monitor phenytoin levels closely, both increased and decreased phenytoin levels have been reported. Risk D: Consider therapy modificationFusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combinationGallium Ga 68 Dotatate: Corticosteroids (Systemic) may diminish the diagnostic effect of Gallium Ga 68 Dotatate.Risk C: Monitor therapyGrowth Hormone Analogs: Corticosteroids (Systemic) may diminish the therapeutic effect of Growth Hormone Analogs. Growth Hormone Analogs may decrease serum concentrations of the active metabolite(s) of Corticosteroids (Systemic).Risk C: Monitor therapyHormonal Contraceptives: CYP3A4 Inducers (Weak) may decrease the serum concentration of Hormonal Contraceptives.Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a weak CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modificationHyaluronidase: Corticosteroids (Systemic) may diminish the therapeutic effect of Hyaluronidase.Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Risk D: Consider therapy modificationImatinib: DexAMETHasone (Systemic) may decrease the serum concentration of Imatinib.Management: Avoid concurrent use of imatinib with dexamethasone when possible.If such a combination must be used, increase imatinib dose by at least 50% and monitor clinical response closely. Risk D: Consider therapy modificationImmune Checkpoint Inhibitors: Corticosteroids (Systemic) may diminish the therapeutic effect of Immune Checkpoint Inhibitors.Management: Carefully consider the need for corticosteroids, at doses of a prednisone-equivalent of 10 mg or more per day, during the initiation of immune checkpoint inhibitor therapy. Use of corticosteroids to treat immune related adverse events is still recommended Risk D: Consider therapy modificationIndium 111 Capromab Pendetide: Corticosteroids (Systemic) may diminish the diagnostic effect of Indium 111 Capromab Pendetide.Risk X: Avoid combinationInebilizumab: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Inebilizumab.Risk C: Monitor therapyInfluenza Virus Vaccines: Corticosteroids (Systemic) may diminish the therapeutic effect of Influenza Virus Vaccines.Management: Administer influenza vaccines at least 2 weeks prior to initiation of systemic corticosteroids at immunosuppressive doses. Influenza vaccines administered less than 14 days prior to or during such therapy should be repeated 3 months after therapy. Risk D: Consider therapy modificationIsoniazid: Corticosteroids (Systemic) may decrease the serum concentration of Isoniazid.Risk C: Monitor therapyLapatinib: DexAMETHasone (Systemic) may decrease the serum concentration of Lapatinib.Management: If therapy overlap cannot be avoided, consider titrating lapatinib gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic breast cancer) or 1,500 mg/day up to 5,500 mg/day (hormone receptor/HER2 positive breast cancer) as tolerated. Risk X: Avoid combinationLeflunomide: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Leflunomide.Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as systemic corticosteroids. Risk D: Consider therapy modificationLenalidomide: DexAMETHasone (Systemic) may enhance the thrombogenic effect of Lenalidomide.Management: Consider using venous thromboembolism prophylaxis (eg, low-molecular weight heparin or warfarin [INR 2.0-3.0]) in patients with multiple myeloma who are receiving lenalidomide and dexamethasone. Risk D: Consider therapy modificationLicorice: May increase the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapyLoop Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Loop Diuretics.Risk C: Monitor therapyLopinavir: DexAMETHasone (Systemic) may decrease the serum concentration of Lopinavir.Management: Consider alternative corticosteroids for coadministration with lopinavir/ritonavir due to the potential for dexamethasone to decrease lopinavir/ritonavir efficacy and result in the development of resistance. Risk D: Consider therapy modificationLutetium Lu 177 Dotatate: Corticosteroids (Systemic) may diminish the therapeutic effect of Lutetium Lu 177 Dotatate.Management: Avoid repeated use of high-doses of corticosteroids during treatment with lutetium Lu 177 dotatate. Use of corticosteroids is still permitted for the treatment of neuroendocrine hormonal crisis. The effects of lower corticosteroid doses is unknown. Risk D: Consider therapy modificationMacimorelin: Corticosteroids (Systemic) may diminish the diagnostic effect of Macimorelin.Risk X: Avoid combinationMethotrimeprazine: Products Containing Ethanol may enhance the adverse/toxic effect of Methotrimeprazine. Specifically, CNS depressant effects may be increased.Management: Avoid products containing alcohol in patients treated with methotrimeprazine. Risk X: Avoid combinationMetyraPONE: Corticosteroids (Systemic) may diminish the diagnostic effect of MetyraPONE.Management: Consider alternatives to the use of the metyrapone test in patients taking systemic corticosteroids. Risk D: Consider therapy modificationMifamurtide: Corticosteroids (Systemic) may diminish the therapeutic effect of Mifamurtide.Risk X: Avoid combinationMiFEPRIStone: May diminish the therapeutic effect of Corticosteroids (Systemic). MiFEPRIStone may increase the serum concentration of Corticosteroids (Systemic). Management: Avoid mifepristone in patients who require long-term corticosteroid treatment of serious illnesses or conditions (eg, for immunosuppression following transplantation). Corticosteroid effects may be reduced by mifepristone treatment. Risk X: Avoid combinationNatalizumab: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Natalizumab.Risk X: Avoid combinationNetupitant: May increase the serum concentration of DexAMETHasone (Systemic). Management: Decrease dexamethasone doses to 12 mg on day 1, and if needed based on the emetic potential of the regimen, 8 mg daily on days 2 to 4 of chemotherapy when administered with netupitant. Risk D: Consider therapy modificationNeuromuscular-Blocking Agents (Nondepolarizing): May enhance the adverse neuromuscular effect of Corticosteroids (Systemic). Increased muscle weakness, possibly progressing to polyneuropathies and myopathies, may occur. Management: If concomitant therapy is required, use the lowest dose for the shortest duration to limit the risk of myopathy or neuropathy. Monitor for new onset or worsening muscle weakness, reduction or loss of deep tendon reflexes, and peripheral sensory decriments Risk D: Consider therapy modificationNicorandil: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nicorandil. Gastrointestinal perforation has been reported in association with this combination.Risk C: Monitor therapyNiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine.Risk C: Monitor therapyNirmatrelvir and Ritonavir: May increase the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapyNonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective).Risk C: Monitor therapyNonsteroidal Anti-Inflammatory Agents (Nonselective): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective).Risk C: Monitor therapyNonsteroidal Anti-Inflammatory Agents (Topical): May enhance the adverse/toxic effect of Corticosteroids (Systemic). Specifically, the risk of gastrointestinal bleeding, ulceration, and perforation may be increased. Risk C: Monitor therapyOcrelizumab: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Ocrelizumab.Risk C: Monitor therapyOfatumumab: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Ofatumumab.Risk C: Monitor therapyOrnidazole: May enhance the adverse/toxic effect of Products Containing Ethanol. Specifically, a disulfiram-like reaction may occur. Risk X: Avoid combinationPhenytoin: May decrease the serum concentration of DexAMETHasone (Systemic). DexAMETHasone (Systemic) may decrease the serum concentration of Phenytoin. DexAMETHasone (Systemic) may increase the serum concentration of Phenytoin. Management: Consider dexamethasone dose increases when combined with phenytoin and monitor closely for reduced steroid efficacy. Monitor phenytoin levels closely when combined with dexamethasone, both increased and decreased phenytoin levels have been reported. Risk D: Consider therapy modificationPidotimod: Corticosteroids (Systemic) may diminish the therapeutic effect of Pidotimod.Risk C: Monitor therapyPimecrolimus: May enhance the immunosuppressive effect of Corticosteroids (Systemic). Risk X: Avoid combinationPneumococcal Vaccines: Corticosteroids (Systemic) may diminish the therapeutic effect of Pneumococcal Vaccines.Risk C: Monitor therapyPoliovirus Vaccine (Live/Trivalent/Oral): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral).Risk X: Avoid combinationPolymethylmethacrylate: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Polymethylmethacrylate. Specifically, the risk for hypersensitivity or implant clearance may be increased.Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modificationQuinolones: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Quinolones. Specifically, the risk of tendonitis and tendon rupture may be increased.Risk C: Monitor therapyRabies Vaccine: Corticosteroids (Systemic) may diminish the therapeutic effect of Rabies Vaccine.Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modificationRilpivirine: DexAMETHasone (Systemic) may decrease the serum concentration of Rilpivirine.Risk X: Avoid combinationRitodrine: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Ritodrine.Risk C: Monitor therapyRubella- or Varicella-Containing Live Vaccines: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines.Risk X: Avoid combinationRuxolitinib (Topical): Corticosteroids (Systemic) may enhance the immunosuppressive effect of Ruxolitinib (Topical).Risk X: Avoid combinationSalicylates: May enhance the adverse/toxic effect of Corticosteroids (Systemic). These specifically include gastrointestinal ulceration and bleeding. Corticosteroids (Systemic) may decrease the serum concentration of Salicylates. Withdrawal of corticosteroids may result in salicylate toxicity. Risk C: Monitor therapySaquinavir: DexAMETHasone (Systemic) may decrease the serum concentration of Saquinavir.Management: Consider alternatives to this combination if possible, due to the potential for decreased saquinavir/ritonavir therapeutic effect and the potential development of resistance. Risk D: Consider therapy modificationSargramostim: Corticosteroids (Systemic) may enhance the therapeutic effect of Sargramostim. Specifically, corticosteroids may enhance the myeloproliferative effects of sargramostim.Risk C: Monitor therapySecnidazole: Products Containing Ethanol may enhance the adverse/toxic effect of Secnidazole.Risk X: Avoid combinationSelpercatinib: CYP3A4 Inducers (Weak) may decrease the serum concentration of Selpercatinib.Risk C: Monitor therapySimeprevir: DexAMETHasone (Systemic) may decrease the serum concentration of Simeprevir.Risk X: Avoid combinationSipuleucel-T: Corticosteroids (Systemic) may diminish the therapeutic effect of Sipuleucel-T.Management: Consider reducing the dose or discontinuing immunosuppressants, such as systemic corticosteroids, prior to initiating sipuleucel-T therapy. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone given for 2 or more weeks are immunosuppressive. Risk D: Consider therapy modificationSirolimus (Conventional): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Conventional).Risk C: Monitor therapySirolimus (Protein Bound): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Protein Bound).Risk C: Monitor therapySodium Benzoate: Corticosteroids (Systemic) may diminish the therapeutic effect of Sodium Benzoate.Risk C: Monitor therapySphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Corticosteroids (Systemic). Risk C: Monitor therapySuccinylcholine: Corticosteroids (Systemic) may enhance the neuromuscular-blocking effect of Succinylcholine.Risk C: Monitor therapyTacrolimus (Systemic): Corticosteroids (Systemic) may decrease the serum concentration of Tacrolimus (Systemic). Conversely, when discontinuing corticosteroid therapy, tacrolimus concentrations may increase.Risk C: Monitor therapyTacrolimus (Systemic): CYP3A4 Inducers (Weak) may decrease the serum concentration of Tacrolimus (Systemic).Risk C: Monitor therapyTacrolimus (Topical): Corticosteroids (Systemic) may enhance the immunosuppressive effect of Tacrolimus (Topical).Risk X: Avoid combinationTalimogene Laherparepvec: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased.Risk X: Avoid combinationTemsirolimus: DexAMETHasone (Systemic) may decrease serum concentrations of the active metabolite(s) of Temsirolimus.Risk C: Monitor therapyTertomotide: Corticosteroids (Systemic) may diminish the therapeutic effect of Tertomotide.Risk X: Avoid combinationThalidomide: DexAMETHasone (Systemic) may enhance the dermatologic adverse effect of Thalidomide. DexAMETHasone (Systemic) may enhance the thrombogenic effect of Thalidomide.Management: Consider using venous thromboembolism prophylaxis (eg, low-molecular-weight heparin or warfarin [INR 2.0 to 3.0]) in patients with multiple myeloma receiving both thalidomide and dexamethasone. Monitor for increased dermatologic adverse effects (eg, rash) Risk D: Consider therapy modificationThiazide and Thiazide-Like Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics.Risk C: Monitor therapyTofacitinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Tofacitinib.Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive. Risk D: Consider therapy modificationTyphoid Vaccine: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Typhoid Vaccine.Risk X: Avoid combinationUbrogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Ubrogepant.Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a weak CYP3A4 inducer. Risk D: Consider therapy modificationUpadacitinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Upadacitinib.Management: Coadministration of upadacitinib with systemic corticosteroids at doses equivalent to greater than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks is not recommended. Risk D: Consider therapy modificationUrea Cycle Disorder Agents: Corticosteroids (Systemic) may diminish the therapeutic effect of Urea Cycle Disorder Agents. More specifically, Corticosteroids (Systemic) may increase protein catabolism and plasma ammonia concentrations, thereby increasing the doses of Urea Cycle Disorder Agents needed to maintain these concentrations in the target range.Risk C: Monitor therapyVaccines (Inactivated/Non-Replicating): Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating).Management: Administer vaccines at least 2 weeks prior to immunosuppressive corticosteroids if possible. If patients are vaccinated less than 14 days prior to or during such therapy, repeat vaccination at least 3 months after therapy if immunocompetence restored. Risk D: Consider therapy modificationVaccines (Live): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Live).Management: Avoid live vaccines during and for 1 month after therapy with immunosuppressive doses of corticosteroids (equivalent to prednisone > 2 mg/kg or 20 mg/day in persons over 10 kg for at least 2 weeks). Give live vaccines prior to therapy whenever possible. Risk D: Consider therapy modificationVitamin K Antagonists (eg, warfarin): Corticosteroids (Systemic) may enhance the anticoagulant effect of Vitamin K Antagonists.Risk C: Monitor therapyVoriconazole: DexAMETHasone (Systemic) may decrease the serum concentration of Voriconazole.Risk C: Monitor therapyYellow Fever Vaccine: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Yellow Fever Vaccine.Risk X: Avoid combinationReproductive ConsiderationsThe manufacturer’s labeling for use of dexamethasone as part of combination therapy for multiple myeloma recommends pregnancy testing prior to use in patients who may become pregnant. Patients who may become pregnant should use effective contraception during therapy and for at least 1 month after the last dexamethasone dose. Consult individual monographs for additional information related to pregnancy testing and contraception when combination therapy is used for multiple myeloma.Dexamethasone may alter the motility of and number of spermatozoa.Pregnancy ConsiderationsDexamethasone crosses the placenta (Brownfoot 2013); and is partially metabolized by placental enzymes to an inactive metabolite (Murphy 2007).Some studies have shown an association between first trimester systemic corticosteroid use and oral clefts or decreased birth weight; however, information is conflicting and may be influenced by maternal dose/indication for use (Lunghi 2010; Park-Wyllie 2000; Pradat 2003). Hypoadrenalism may occur in newborns following maternal use of corticosteroids during pregnancy; monitor.Dexamethasone is classified as a fluorinated corticosteroid. When systemic corticosteroids are needed in pregnancy for rheumatic disorders, nonfluorinated corticosteroids (eg, prednisone) are preferred. Chronic high doses should be avoided for the treatment of maternal disease (ACR [Sammaritano 2020]).Use of the overnight dexamethasone 1 mg suppression test for Cushing syndrome is not recommended during pregnancy due to the increased risk of false positives. In addition, dexamethasone is generally avoided for the treatment of pregnant patients with adrenal insufficiency (ES [Nieman 2008]; ESE [Luger 2021]).Antenatal corticosteroid administration promotes fetal lung maturity and is associated with the reduction of intraventricular hemorrhage, necrotizing enterocolitis, neonatal mortality, and respiratory distress syndrome. A single course of dexamethasone is recommended for patients between 24 0/7 and 33 6/7 weeks' gestation who are at risk of delivering within 7 days. This recommendation includes those with ruptured membranes or multiple gestations. A single course of dexamethasone may be considered for patients beginning at 23 0/7 weeks' gestation who are at risk of delivering within 7 days, in consultation with the family regarding resuscitation. In addition, a single course of dexamethasone may be given to patients between 34 0/7 weeks and 36 6/7 weeks who are at risk of preterm delivery within 7 days and who have not previously received corticosteroids if induction or delivery will proceed ≥24 hours and ≤7 days; delivery should not be delayed for administration of antenatal corticosteroids. Use of concomitant tocolytics is not currently recommended and administration of late preterm corticosteroids has not been evaluated in patients with intrauterine infection, multiple gestations, pregestational diabetes, or patients who delivered previously by cesarean section at term. Multiple repeat courses are not recommended. However, in patients with pregnancies less than 34 weeks' gestation at risk for delivery within 7 days and who had a course of antenatal corticosteroids >14 days prior, a single repeat course may be considered; use of a repeat course in patients with preterm prelabor rupture of membranes is controversial (ACOG 2016; ACOG 2017; ACOG 2020).Dexamethasone is used off label in the management of COVID-19. Use is recommended for hospitalized pregnant patients with COVID-19 who require mechanical ventilation, or who require supplemental oxygen without mechanical ventilation (NIH 2022). In patients who do not require dexamethasone for fetal lung maturity, or in those who have already completed a course of dexamethasone to enhance fetal lung development, treatment recommendations are available using alternative corticosteroids which have more limited placental transfer and may provide less fetal risk. A treatment algorithm is available for pregnant patients with severe or critical COVID-19 requiring corticosteroids for fetal lung maturation and those who do not (Saad 2020). The risk of severe illness from COVID-19 infection is increased in symptomatic pregnant patients compared to nonpregnant patients (ACOG 2022). Information related to the treatment of COVID-19 during pregnancy continues to emerge; refer to current guidelines for the treatment of pregnant patients.Some products contain alcohol, benzyl alcohol or sodium sulfite; use of preservative-free or alternative formulations in pregnancy is recommended.Breastfeeding ConsiderationsCorticosteroids are present in breast milk; information specific to dexamethasone has not been located.The manufacturer notes that when used systemically, maternal use of corticosteroids have the potential to cause adverse events in a breastfeeding infant (eg, growth suppression, interfere with endogenous corticosteroid production).Single doses of dexamethasone are considered compatible with breastfeeding; information related to prolonged use is not available (WHO 2002). If there is concern about exposure to the infant, some guidelines recommend waiting 4 hours after the maternal dose of an oral systemic corticosteroid before breastfeeding in order to decrease potential exposure to the breastfed infant (based on a study using prednisolone) (Leachman 2006; Makol 2011; Ost 1985). Dexamethasone is classified as a fluorinated corticosteroid. When systemic corticosteroids are needed in a lactating patient for rheumatic disorders, low doses of nonfluorinated corticosteroids (eg, prednisone) are preferred (ACR [Sammaritano 2020]). Due to the potential for serious adverse reactions in the breastfeeding infant, some manufacturers recommend a decision be made to discontinue breastfeeding or to discontinue the drug, considering the importance of treatment to the mother. The manufacturer's labeling for use of dexamethasone as part of combination therapy for multiple myeloma recommends breastfeeding be discontinued during therapy and for 2 weeks after the last dexamethasone dose.Dietary ConsiderationsMay be taken with meals to decrease GI upset. May need diet with increased potassium, pyridoxine, vitamin C, vitamin D, folate, calcium, and phosphorus.Monitoring ParametersHb, occult blood loss, BP, serum potassium, blood glucose, creatine kinase (if symptoms of myopathy occur), bone mineral density; intraocular pressure with systemic use >6 weeks; consider routine eye exams with chronic use; weight and height in children; hypothalamic-pituitary-adrenal axis suppression.Oncology patients: Evaluate pregnancy status (in females of reproductive potential when receiving for multiple myeloma treatment). The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.Mechanism of ActionDexamethasone is a long-acting corticosteroid with minimal sodium-retaining potential. It decreases inflammation by suppression of neutrophil migration, decreased production of inflammatory mediators, and reversal of increased capillary permeability; suppresses normal immune response. Dexamethasone induces apoptosis in multiple myeloma cells. Dexamethasone's mechanism of antiemetic activity is unknown.Pharmaco*kineticsOnset of action: IV: Rapid.Immune thrombocytopenia: Oral: Initial response: 2 to 14 days; Peak response: 4 to 28 days (Neunert 2011).Duration: IV: Short.Absorption: Oral: 61% to 86% (Czock 2005).Metabolism: Hepatic.Half-life elimination:Extremely low birth-weight infants with BPD: 9.26 ± 3.34 hours (range: 5.85 to 16.1 hours) (Charles 1993).Children 4 months to 16 years: 4.34 ± 4.14 hours (range: 2.33 to 9.54 hours) (Richter 1983).Adults: Oral: 4 ± 0.9 hours (Czock 2005); IV: ~1 to 5 hours (Hochhaus 2001; Miyabo 1981; Rohdewald 1987; Tóth 1999).Time to peak, serum: Oral: 1 to 2 hours (Czock 2005); IM: ~30 to 120 minutes (Egerman 1997; Hochhaus 2001); IV: 5 to 10 minutes (free dexamethasone) (Miyabo 1981; Rohdewald 1987).Excretion: Urine (~10%) (Duggan 1975; Miyabo 1981).Pricing: USConcentrate (Dexamethasone Intensol Oral)1 mg/mL (per mL): $1.07Elixir (Dexamethasone Oral)0.5 mg/5 mL (per mL): $0.11 - $0.27Kit (DoubleDex Injection)10 mg/mL (per each): $598.00Kit (MAS Care-Pak Injection)10 mg/mL (per each): $605.00Solution (Dexamethasone Oral)0.5 mg/5 mL (per mL): $0.27Solution (Dexamethasone Sod Phosphate PF Injection)10 mg/mL (per mL): $2.10 - $8.22Solution (Dexamethasone Sodium Phosphate Injection)4 mg/mL (per mL): $0.93 - $3.4710 mg/mL (per mL): $1.49 - $1.7220 mg/5 mL (per mL): $0.21 - $1.51100 mg/10 mL (per mL): $0.48 - $1.70120 mg/30 mL (per mL): $0.39 - $1.63Tablet Therapy Pack (Dexamethasone Oral)1.5MG (21) (per each): $8.06 - $8.541.5MG (35) (per each): $8.551.5MG (51) (per each): $8.54Tablet Therapy Pack (Dxevo 11-Day Oral)1.5 mg (per each): $17.79Tablet Therapy Pack (HiDex 6-Day Oral)1.5MG (21) (per each): $33.29Tablet Therapy Pack (TaperDex 12-Day Oral)1.5MG (49) (per each): $5.68Tablet Therapy Pack (TaperDex 6-Day Oral)1.5 mg (per each): $10.801.5MG (21) (per each): $10.80Tablet Therapy Pack (TaperDex 7-Day Oral)1.5MG (27) (per each): $8.66Tablets (Dexamethasone Oral)0.5 mg (per each): $0.14 - $0.210.75 mg (per each): $0.25 - $0.271 mg (per each): $0.30 - $0.371.5 mg (per each): $0.48 - $3.702 mg (per each): $0.59 - $0.744 mg (per each): $1.19 - $1.206 mg (per each): $1.78 - $1.90Tablets (Hemady Oral)20 mg (per each): $31.31Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalAacidexam (BE);Alin (CR, DO, GT, HN, NI, PA, SV);Asiadexa (VN);Camidexon (ID);Corodex (UY);Cortyk (CL);D Cort (BD);Decadron (AE, BH, CO, CY, EC, IT, JO, KW, LB, PY, QA, SA);Decan (PH, SG);Decasone (ZA);Decdan (IN);Dectancyl (VN);Deltasone (EG);Desalark (IT);Dexa-Sine (BE);Dexacor (BD);Dexacort Forte (IL);Dexaflam (DE);Dexafree (CH, FR, PL, PT);Dexamax (PH);Dexamed (CZ, JO, RO, SG, TR);Dexamed Elixir (LK);Dexamet Solution for Injection (HK);Dexanocorten (EG);Dexasone (EG, MY);Dexazone (QA);Dexcor (BD);Dexmethsone (AU, NZ);Dexo (ET);Dexona (ET, IN);Dexona-E (LK);Dexone (ZW);Dexovit (LK);Dexsol (IE);Fortecortin (AT, BG, CH, DE, ES);Lenadex (JP);Lodexa (TH);Lodexa-5 (TH);Maradex (VE);Martapan (GB);Medicort (PE);Meradexone (BD);Metacort (PH);Methodex (LK);Millicorten (QA);Naxidex (LK);Nexadron Oftal (AR);Odeson (BD);Oftan Dexa (EE);Opnol (SE);Oradexon (CL, FI, ID, NL, PT, SA);Ordex (BD);Ronic (ET);Sonexa (BD);Spersadex (CH, DE, HK, NO, ZA);Sterodex (IL);Steron (BD);Vedex (LK);Vextasone (MY);Vherdex (PH);Visumetazone (IT);Wymesone (IN)For country code abbreviations (show table)Abouir K, Gosselin P, Guerrier S, et al. Dexamethasone exposure in normal-weight and obese hospitalized COVID-19 patients: an observational exploratory trial. Clin Transl Sci. 2022;15(7):1796-1804. doi:10.1111/cts.13297 [PubMed 35706350]Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319. [PubMed 11487763]Akahoshi S, Hasegawa Y. Steroid-induced iatrogenic adrenal insufficiency in children: a literature review. Endocrines. 2020;1(2):125-137. doi:10.3390/endocrines1020012Allan SG, Leonard RCF. Dexamethasone antiemesis and side-effects. Lancet. 1986;1(8488):1035. [PubMed 2871314]Allolio B. Extensive expertise in endocrinology. Adrenal crisis. Eur J Endocrinol. 2015;172(3):R115-R124. doi:10.1530/EJE-14-0824 [PubMed 25288693]American Academy of Pediatrics (AAP). In: Kimberlin DW, Brady MT, Jackson MA, Long SA, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics; 2018.American Academy of Pediatrics (AAP). Statement of endorsem*nt-congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency. Pediatrics. 2010; 126(5):151. Accessed October 27, 2014. http://pediatrics.aappublications.org/content/126/5/1051.extract.American Academy of Pediatrics Committee on Infectious Diseases. Dexamethasone Therapy for Bacterial Meningitis in Infants and Children. Pediatrics. 1990;86(1):130-133. [PubMed 2193301]American College of Obstetricians and Gynecologists (ACOG) Committee on Obstetric Practice. ACOG Committee Opinion No. 713: Antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol. 2017;130(2):e102-e109. doi:10.1097/AOG.0000000000002237 [PubMed 28742678]American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins–Obstetrics. ACOG Practice Bulletin No. 171: Management of preterm labor. Obstet Gynecol. 2016;128(4):e155-e164. doi:10.1097/AOG.0000000000001711 [PubMed 27661654]American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins–Obstetrics. ACOG Practice Bulletin No. 217: Prelabor rupture of membranes. Obstet Gynecol. 2020;135(3):e80‐e97. doi:10.1097/AOG.0000000000003700 [PubMed 32080050]American College of Obstetricians and Gynecologists (ACOG). COVID-19 FAQs for obstetricians-gynecologists, obstetrics. https://www.acog.org/clinical-information/physician-faqs/covid-19-faqs-for-ob-gyns-obstetrics. Accessed August 1, 2022.American College of Radiology (ACR) Committee on Drugs and Contrast Media. ACR manual on contrast media. https://www.acr.org/-/media/ACR/Files/Clinical-Resources/Contrast_Media.pdf. Published 2021. Accessed January 3, 2022.Anene O, Meert KL, Uy H, Simpson P, Sarnaik AP. Dexamethasone for the prevention of postextubation airway obstruction: a prospective, randomized, double-blind, placebo-controlled trial. Crit Care Med. 1996;24(10):1666-1669. [PubMed 8874303]Annane D, Pastores SM, Rochwerg B, et al. Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017. Crit Care Med. 2017;45(12):2078-2088. doi: 10.1097/CCM.0000000000002737. [PubMed 28938253]Arnold DM. Initial treatment of immune thrombocytopenia (ITP) in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 19, 2022.Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007:110, 176.Attal M, Richardson PG, Rajkumar SV, et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study [published correction appears in Lancet. 2019;394(10214):2072]. Lancet. 2019;394(10214):2096-2107. doi:10.1016/S0140-6736(19)32556-5 [PubMed 31735560]Bahal N, Nahata MC. The role of corticosteroids in infants and children with bacterial meningitis. DICP. 1991;25(5):542-545. [PubMed 2068839]Baldwin D, Apel J. Management of hyperglycemia in hospitalized patients with renal insufficiency or steroid-induced diabetes. Curr Diab Rep. 2013;13(1):114-120. doi:10.1007/s11892-012-0339-7 [PubMed 23090580]Based on expert opinion.Benghiat H, Sanghera P, Stange D, et al. Dexamethasone-related adrenal insufficiency in patients with brain and skull base tumours. Support Care Cancer. 2018;26(12):4031-4038. doi:10.1007/s00520-018-4264-4 [PubMed 29858690]Bernini JC, Rogers ZR, Sandler ES, et al. Beneficial effect of intravenous dexamethasone in children with mild to moderately severe acute chest syndrome complicating sickle cell disease. Blood. 1998;92:3082-3089. [PubMed 9787142]Berris KK, Repp AL, Kleerekoper M. Glucocorticoid-induced osteoporosis. Curr Opin Endocrinol Diabetes Obes. 2007;14(6):446-450. doi:10.1097/MED.0b013e3282f15407 [PubMed 17982350]Bhimraj A, Morgan RL, Shumaker AH, et al. Infectious Diseases Society of America (IDSA) guidelines on the treatment and management of patients with COVID-19. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/#toc-5. Updated June 29, 2022. Accessed August 10, 2022.Bjornson CL, Klassen TP, Williamson J, et al. A randomized trial of a single dose of oral dexamethasone for mild croup. N Engl J Med. 2004;351(13):1306-1313. [PubMed 15385657]Bonaventura A, Montecucco F. Steroid-induced hyperglycemia: An underdiagnosed problem or clinical inertia? A narrative review. Diabetes Res Clin Pract. 2018;139:203-220. doi:10.1016/j.diabres.2018.03.006 [PubMed 29530386]Bornstein SR. Predisposing factors for adrenal insufficiency. N Engl J Med. 2009;360(22):2328-2339. doi:10.1056/NEJMra0804635 [PubMed 19474430]Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(2):364-389. doi:10.1210/jc.2015-1710. [PubMed 26760044]Boumpas DT, Chrousos GP, Wilder RL, Cupps TR, Balow JE. Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann Intern Med. 1993;119(12):1198-1208. doi:10.7326/0003-4819-119-12-199312150-00007 [PubMed 8239251]Bowden SA, Henry R. Pediatric Adrenal insufficiency: Diagnosis, management, and new therapies. Int J Pediatr. 2018;2018:1739831. doi:10.1155/2018/1739831 [PubMed 30515225]Briot K, Roux C. Glucocorticoid-induced osteoporosis. RMD Open. 2015;1(1):e000014. doi:10.1136/rmdopen-2014-000014 [PubMed 26509049]Brownfoot FC, Gagliardi DI, Bain E, Middleton P, Crowther CA. Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2013;(8):CD006764. doi:10.1002/14651858.CD006764.pub3 [PubMed 23990333]Buckley L, Fuyatt G, Fink HA, et al. 2017 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheumatology. 2017;69(8):1521-1537.Buckley L, Humphrey MB. Glucocorticoid-induced osteoporosis. N Engl J Med. 2018;379(26):2547-2556. doi:10.1056/NEJMcp1800214 [PubMed 30586507]Caplan A, Fett N, Rosenbach M, Werth VP, Micheletti RG. Prevention and management of glucocorticoid-induced side effects: A comprehensive review: Gastrointestinal and endocrinologic side effects. J Am Acad Dermatol. 2017;76(1):11-16. doi:10.1016/j.jaad.2016.02.1239 [PubMed 27986133]Carney N, Totten AM, O'Reilly C, et al; Brain Trauma Foundation. Guidelines for the management of severe traumatic brain injury, fourth edition [published online September 20, 2016]. Neurosurgery. doi:10.1227/NEU.0000000000001432. [PubMed 27654000]Centeno LM, Moore ME. Preferred intraarticular corticosteroids and associated practice: a survey of members of the American College of Rheumatology. Arthritis Care Res. 1994;7(3):151-155. [PubMed 7727555]Centers for Disease Control (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm [PubMed 6810084]Chang SM, Messersmith H, Ahluwalia M, et al. Anticonvulsant prophylaxis and steroid use in adults with metastatic brain tumors: summary of SNO and ASCO endorsem*nt of the Congress of Neurological Surgeons guidelines. Neuro Oncol. 2019;21(4):424-427. doi:10.1093/neuonc/noz034. [PubMed 30883663]Chang YP. Evidence for adverse effect of perinatal glucocorticoid use on the developing brain. Korean J Pediatr. 2014;57(3):101-109. doi:10.3345/kjp.2014.57.3.101 [PubMed 24778691]Chanimov M, Koren-Michowitz M, Cohen ML, Pilipodi S, Bahar M. Tumor lysis syndrome induced by dexamethasone. Anesthesiology. 2006;105(3):633-634. doi:10.1097/00000542-200609000-00042 [PubMed 16932011]Chari A, Rodriguez-Otero P, McCarthy H, et al. Subcutaneous daratumumab plus standard treatment regimens in patients with multiple myeloma across lines of therapy (PLEIADES): an open-label phase II study. Br J Haematol. 2021;192(5):869-878. doi:10.1111/bjh.16980 [PubMed 33216361]Chari A, Suvannasankha A, Fay JW, et al. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood. 2017;130(8):974-981. doi:10.1182/blood-2017-05-785246. [PubMed 28637662]Chari A, Vogl DT, Gavriatopoulou M, et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019;381(8):727-738. doi:10.1056/NEJMoa1903455 [PubMed 31433920]Charles B, Schild P, Steer P, Cartwright D, Donovan T. Pharmaco*kinetics of dexamethasone following single-dose intravenous administration to extremely low birth weight infants. Dev Pharmacol Ther. 1993;20(3-4):205-210. [PubMed 7828455]Chen JS, Wu JM, Chen YJ, Yeh TF. Pulsed high-dose dexamethasone therapy in children with chronic idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol. 1997;19(6):526-529. [PubMed 9407939]Cinvanti (aprepitant IV) [prescribing information]. San Diego, CA: Heron Therapeutics, Inc; November 2017.Ciriaco M, Ventrice P, Russo G, et al. Corticosteroid-related central nervous system side effects. J Pharmacol Pharmacother. 2013;4(suppl 1):S94-S98. doi:10.4103/0976-500X.120975 [PubMed 24347992]Colman I, Friedman BW, Brown MD, et al. Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomised controlled trials for preventing recurrence. BMJ. 2008;336(7657):1359-1361. doi:10.1136/bmj.39566.806725.BE [PubMed 18541610]Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med. 2003;348(8):727-734. doi:10.1056/NEJMra020529. [PubMed 12594318]Coursin DB, Wood KE. Corticosteroid supplementation for adrenal insufficiency. JAMA. 2002;287(2):236-240. doi:10.1001/jama.287.2.236 [PubMed 11779267]Couser RJ, Ferrara TB, Falde B, et al. Effectiveness of dexamethasone in preventing extubation failure in preterm infants at increased risk for airway edema. J Pediatr. 1992;121(4):591-596. [PubMed 1403397]Cruz MN, Stewart G, Rosenberg N. Use of dexamethasone in the outpatient management of acute laryngotracheitis. Pediatrics. 1995;96(2 Pt 1):220-223. [PubMed 7630673]Czock D, Keller F, Rasche FM, Häussler U. Pharmaco*kinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmaco*kinet. 2005;44(1):61-98. doi:10.2165/00003088-200544010-00003 [PubMed 15634032]Davis PG and Henderson-Smart DJ. Intravenous dexamethasone for extubation of newborn infants. Cochrane Database Syst Rev. 2001;(4):CD000308. [PubMed 11687075]de Gans J, van de Beek D; European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002;347(20):1549-1556. doi:10.1056/NEJMoa021334. [PubMed 12432041]De Laet MH, Dassonville M, Johansson A, et al. Small-bowel perforation in very low birth weight neonates treated with high-dose dexamethasone. Eur J Pediatr Surg. 2000;10(5):323-327. doi:10.1055/s-2008-1072384 [PubMed 11194544]De Oliveira GS Jr, Castro-Alves LJ, Ahmad S, Kendall MC, McCarthy RJ. Dexamethasone to prevent postoperative nausea and vomiting: an updated meta-analysis of randomized controlled trials. Anesth Analg. 2013;116(1):58-74. doi:10.1213/ANE.0b013e31826f0a0a [PubMed 23223115]Decadron (dexamethasone) [prescribing information]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; May 2019.Delaleu J, Destere A, Hachon L, Declèves X, Lloret-Linares C. Glucocorticoids dosing in obese subjects: a systematic review. Therapie. 2019;74(4):451-458. doi:10.1016/j.therap.2018.11.016 [PubMed 30928086]Desandre PL, Quest TE. Management of cancer-related pain. Hematol Oncol Clin North Am. 2010;24(3):643-658. [PubMed 20488359]Dexabliss (dexamethasone) [prescribing information]. Biloxi, MS: Levins Pharmaceuticals; March 2020.Dexamethasone elixir [prescribing information]. Morton Grove, IL: Morton Grove Pharmaceuticals; April 2008.Dexamethasone, Granisetron, or Both for the Prevention of Nausea and Vomiting During Chemotherapy for Cancer. The Italian Group for Antiemetic Research. N Engl J Med. 1995;332(1):1-5. [PubMed 7990859]Dexamethasone Injection, USP (dexamethasone sodium phosphate) [prescribing information]. Lake Zurich, IL: Fresenius Kabi; November 2017.Dexamethasone Injection, USP (dexamethasone sodium phosphate) [prescribing information]. Rockford, IL: Mylan; December 2015.Dexamethasone tablets, dexamethasone oral solution, Intensol [prescribing information]. East Windsor, New Jersey: Novitium Pharma LLC; June 2022.Dexamethasone tablets and dexamethasone oral solution [prescribing information]. East Windsor, New Jersey: Novitium Pharma LLC; June 2022.DexPak 13 Day TaperPak, 10 Day TaperPak, and 6 Day TaperPak (dexamethasone) [prescribing information]. Richmond, VA: ECR; June 2011.Dickerson JE Jr, Dotzel E, Clark AF. Steroid-induced cataract: new perspective from in vitro and lens culture studies. Exp Eye Res. 1997;65(4):507-516. doi:10.1006/exer.1997.0359 [PubMed 9464184]Dietrich J, Rao K, Pastorino S, Kesari S. Corticosteroids in brain cancer patients: benefits and pitfalls. Expert Rev Clin Pharmacol. 2011;4(2):233-242. doi:10.1586/ecp.11.1 [PubMed 21666852]Dimopoulos MA, Dytfeld D, Grosicki S, et al. Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma. N Engl J Med. 2018;379(19):1811-1822. doi: 10.1056/NEJMoa1805762. [PubMed 30403938]Dimopoulos MA, Moreau P, Palumbo A, et al; ENDEAVOR Investigators. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016a;17(1):27-38. doi:10.1016/S1470-2045(15)00464-7. [PubMed 26671818]Dimopoulos MA, Oriol A, Nahi H, et al; POLLUX Investigators. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016b;375(14):1319-1331. [PubMed 27705267]Dimopoulos MA, Sonneveld P, Leung N, et al. International Myeloma Working Group recommendations for the diagnosis and management of myeloma-related renal impairment. J Clin Oncol. 2016c;34(13):1544-1557. [PubMed 26976420]Dimopoulos M, Quach H, Mateos MV, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Lancet. 2020;396(10245):186-197. doi:10.1016/S0140-6736(20)30734-0 [PubMed 32682484]Dimopoulos MA, Terpos E, Boccadoro M, et al; APOLLO Trial Investigators. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(6):801-812. doi:10.1016/S1470-2045(21)00128-5 [PubMed 34087126]Dineen R, Thompson CJ, Sherlock M. Adrenal crisis: prevention and management in adult patients. Ther Adv Endocrinol Metab. 2019;10:2042018819848218. doi:10.1177/2042018819848218 [PubMed 31223468]Dixon WG, Abrahamowicz M, Beauchamp ME, et al. Immediate and delayed impact of oral glucocorticoid therapy on risk of serious infection in older patients with rheumatoid arthritis: a nested case-control analysis. Ann Rheum Dis. 2012;71(7):1128-1133. doi:10.1136/annrheumdis-2011-200702 [PubMed 22241902]Doyle LW, Davis PG, Morley CJ, et al. Low-Dose Dexamethasone Facilitates Extubation Among Chronically Ventilator-Dependent Infants: A Multicenter, International, Randomized, Controlled Trial. Pediatrics. 2006;117(1):75-83. [PubMed 16396863]Drozdowicz LB, Bostwick JM. Psychiatric adverse effects of pediatric corticosteroid use. Mayo Clin Proc. 2014;89(6):817-834. doi:10.1016/j.mayocp.2014.01.010 [PubMed 24943696]Duggan DE, Matalia N, Ditzler, CA, et al. Bioavailability of oral dexamethasone. Clin Pharmacol Ther. 1975;18(2):205-209. [PubMed 1097154]Dulek DE, Fuhlbrigge RC, Tribble AC, et al. Multidisciplinary guidance regarding the use of immunomodulatory therapies for acute coronavirus disease 2019 in pediatric patients. J Pediatric Infect Dis Soc. 2020;9(6):716-737. doi:10.1093/jpids/piaa098 [PubMed 32808988]Dupuis LL, Boodhan S, Holdsworth M, et al; Pediatric Oncology Group of Ontario. Guideline for the prevention of acute nausea and vomiting due to antineoplastic medication in pediatric cancer patients. Pediatr Blood Cancer. 2013;60(7):1073-1082. doi:10.1002/pbc.24508. [PubMed 23512831]Durand M, Sardesai S, McEvoy C. Effects of early dexamethasone therapy on pulmonary mechanics and chronic lung disease in very low birth weight infants: a randomized, controlled trial. Pediatrics. 1995;95(4):584-590. [PubMed 7700763]Durie BGM, ho*ring A, Abidi MH, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017;389(10068):519-527. doi:10.1016/S0140-6736(16)31594-X [PubMed 28017406]Durie BGM, ho*ring A, Sexton R, et al. Longer term follow-up of the randomized phase III trial SWOG S0777: bortezomib, lenalidomide and dexamethasone vs. lenalidomide and dexamethasone in patients (Pts) with previously untreated multiple myeloma without an intent for immediate autologous stem cell transplant (ASCT). Blood Cancer J. 2020;10(5):53. doi:10.1038/s41408-020-0311-8 [PubMed 32393732]Dxevo (dexamethasone) [prescribing information]. Ocean Springs, MS: Phlight Pharma.; June 2019.Egerman RS, Pierce WF 4th, Andersen RN, Umstot ES, Carr TL, Sibai BM. A comparison of the bioavailability of oral and intramuscular dexamethasone in women in late pregnancy. Obstet Gynecol. 1997;89(2):276-280. [PubMed 9015035]Erstad BL. Dosing of medications in morbidly obese patients in the intensive care unit setting. Intensive Care Med. 2004;30(1):18-32. doi:10.1007/s00134-003-2059-6. [PubMed 14625670]Facon T, Kumar S, Plesner T, et al; MAIA Trial Investigators. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380(22):2104-2115. doi:10.1056/NEJMoa1817249. [PubMed 31141632]Facon T, Venner CP, Bahlis NJ, et al. Oral ixazomib, lenalidomide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma. Blood. 2021;137(26):3616-3628. doi:10.1182/blood.2020008787 [PubMed 33763699]Fardet L, Petersen I, Nazareth I. Suicidal behavior and severe neuropsychiatric disorders following glucocorticoid therapy in primary care. Am J Psychiatry. 2012;169(5):491-497. doi:10.1176/appi.ajp.2011.11071009 [PubMed 22764363]Fong AC, Cheung NW. The high incidence of steroid-induced hyperglycaemia in hospital. Diabetes Res Clin Pract. 2013;99(3):277-280. doi:10.1016/j.diabres.2012.12.023 [PubMed 23298665]Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi:10.1210/jc.2015-4061. [PubMed 26934393]Furst DE, Saag KG. Glucocorticoid withdrawal. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 22, 2022.Gahart BL, Nazareno AR, Ortega MQ. Gahart’s 2021 Intravenous Medications: A Handbook for Nurses and Health Professionals. 37th ed. Elsevier; 2021.Gal P, Reed M. Medications. In: Kliegman RM, Behrman RE, Jenson HB, et al, eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, PA: Saunders Elsevier; 2007: 2955-2999.Gallagher SA, Hackett P. Acute mountain sickness and high altitude cerebral edema. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 1, 2021.Gan TJ, Belani KG, Bergese S, et al. Fourth consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg. 2020;131(2):411-448. doi:10.1213/ANE.0000000000004833 [PubMed 32467512]García Rodríguez LA, Lin KJ, Hernández-Díaz S, Johansson S. Risk of upper gastrointestinal bleeding with low-dose acetylsalicylic acid alone and in combination with clopidogrel and other medications. Circulation. 2011;123(10):1108-1115. doi:10.1161/CIRCULATIONAHA.110.973008 [PubMed 21357821]George MD, Baker JF, Winthrop K, et al. Risk for serious infection with low-dose glucocorticoids in patients with rheumatoid arthritis: a cohort study. Ann Intern Med. 2020;173(11):870-878. doi:10.7326/M20-1594 [PubMed 32956604]George R, Jeba J, Ramkumar G, Chacko AG, Tharyan P. Interventions for the treatment of metastatic extradural spinal cord compression in adults. Cochrane Database Syst Rev. 2015;(9):CD006716. doi:10.1002/14651858.CD006716.pub3. [PubMed 26337716]Ghisdal L, Van Laecke S, Abramowicz MJ, Vanholder R, Abramowicz D. New-onset diabetes after renal transplantation: risk assessment and management. Diabetes Care. 2012;35(1):181-188. doi:10.2337/dc11-1230 [PubMed 22187441]Giuliana G, Marcianò V, De Cosimo D, D'Angelo M. Effetti sui tessuti parodontali di uno spazzolino a setole "ammortizzate" (Analisi al S.E.M.) [Effect on periodontal tissue of a "cushioned" bristle brush. (S.E.M. analysis)]. Stomatol Mediterr. 1990;10(2):77-82. Italian. [PubMed 2218744]Gill N, Sirizzotti N, Johnson D, et al. Endogenous glucocorticoid response to single-dose dexamethasone for croup in children: A pharmacodynamic study. Pediatr Emerg Care. 2020;36(1):50-56. doi:10.1097/PEC.0000000000001142 [PubMed 28398936]Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. Updated 2020. Accessed May 6, 2020. https://ginasthma.org/wp-content/uploads/2020/04/GINA-2020-full-report_-final-_wms.pdf.Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention.https://ginasthma.org/gina-reports/. Updated 2022. Accessed October 11, 2022.Goedert JJ, Vitale F, Lauria C, et al. Risk factors for classical Kaposi's sarcoma. J Natl Cancer Inst. 2002;94(22):1712-1718. [PubMed 12441327]Gordon P, Rutledge J, Sawin R, Thomas S, Woodrum D. Early postnatal dexamethasone increases the risk of focal small bowel perforation in extremely low birth weight infants. J Perinatol. 1999;19(8 Pt 1):573-577. doi:10.1038/sj.jp.7200269 [PubMed 10645522]Gordon PV, Young ML, Marshall DD. Focal small bowel perforation: an adverse effect of early postnatal dexamethasone therapy in extremely low birth weight infants. J Perinatol. 2001;21(3):156-160. doi:10.1038/sj.jp.7200520 [PubMed 11503101]Grosicki S, Simonova M, Spicka I, et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet. 2020;396(10262):1563-1573. doi:10.1016/S0140-6736(20)32292-3 [PubMed 33189178]Gupta P, Bhatia V. Corticosteroid physiology and principles of therapy. Indian J Pediatr. 2008;75(10):1039-1044. [PubMed 19023528]Guslandi M. Steroid ulcers: Any news? World J Gastrointest Pharmacol Ther. 2013;4(3):39-40. doi:10.4292/wjgpt.v4.i3.39 [PubMed 23919213]Hamrahian AH, Sanziana R, Milan S. The management of the surgical patient taking glucocorticoids. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 8, 2020.Haran M, Schattner A, Kozak N, Mate A, Berrebi A, Shvidel L. Acute steroid myopathy: a highly overlooked entity. QJM. 2018;111(5):307-311. doi:10.1093/qjmed/hcy031 [PubMed 29462474]Haywood A, Good P, Khan S, et al. Corticosteroids for the management of cancer-related pain in adults. Cochrane Database Syst Rev. 2015;2015(4):CD010756. doi:10.1002/14651858.CD010756.pub2 [PubMed 25908299]Hedlund-Treutiger I, Henter JI, Elinder G. Randomized study of IVIg and high-dose dexamethasone therapy for children with chronic idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol. 2003;25(2):139-44. [PubMed 12571466]Hegenbarth MA; American Academy of Pediatrics Committee on Drugs. Preparing for pediatric emergencies: drugs to consider. Pediatrics. 2008;121(2):433-443. [PubMed 18245435]Hemady (dexamethasone) [prescribing information]. East Windsor, NJ: Acrotech Biopharma Inc; July 2022.Henderson LA, Canna SW, Friedman KG, et al. American College of Rheumatology (ACR) clinical guidance for multisystem inflammatory syndrome in children associated with SARS-CoV-2 and hyperinflammation in pediatric COVID-19: Version 3. Arthritis Rheumatol. Published online February 3, 2022. doi:10.1002/art.42062 [PubMed 35118829]Hernández-Díaz S, Rodríguez LA. Steroids and risk of upper gastrointestinal complications. Am J Epidemiol. 2001;153(11):1089-1093. doi:10.1093/aje/153.11.1089 [PubMed 11390328]Hesketh PJ. Prevention and treatment of chemotherapy-induced nausea and vomiting in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 16, 2020b.Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: ASCO guideline update. J Clin Oncol. 2020a;38(24):2782-2797. doi:10.1200/JCO.20.01296 [PubMed 32658626]Hochhaus G, Barth J, al-Fayoumi S, et al. Pharmaco*kinetics and pharmacodynamics of dexamethasone sodium-m-sulfobenzoate (DS) after intravenous and intramuscular administration: a comparison with dexamethasone phosphate (DP). J Clin Pharmacol. 2001;41(4):425-434. [PubMed 11304899]Holdsworth MT, Raisch DW, Frost J. Acute and delayed nausea and emesis control in pediatric oncology patients. Cancer. 2006;106(4):931-940. [PubMed 16404740]Honoré PM, Jacobs R, De Waele E, et al. What do we know about steroids metabolism and 'PK/PD approach' in AKI and CKD especially while on RRT--current status in 2014. Blood Purif. 2014;38(2):154-157. doi:10.1159/000368390 [PubMed 25471548]Hopkins RL, Leinung MC. Exogenous Cushing's syndrome and glucocorticoid withdrawal. Endocrinol Metab Clin North Am. 2005;34(2):371-84, ix. doi:10.1016/j.ecl.2005.01.013 [PubMed 15850848]Horby P, Lim WS, Emberson J, et al. Effect of dexamethasone in hospitalized patients with COVID-19: preliminary report. Published June 22, 2020. Accessed June 25, 2020. https://www.medrxiv.org/content/10.1101/2020.06.22.20137273v1.Huang Y, Cai X, Song X, et al. Steroids for preventing recurrence of acute severe migraine headaches: a meta-analysis. Eur J Neurol. 2013;20(8):1184-1190. doi:10.1111/ene.12155 [PubMed 23577697]Husebye ES, Allolio B, Arlt W, et al. Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J Intern Med. 2014;275(2):104-115. doi:10.1111/joim.12162 [PubMed 24330030]Huscher D, Thiele K, Gromnica-Ihle E, et al. Dose-related patterns of glucocorticoid-induced side effects. Ann Rheum Dis. 2009;68(7):1119-1124. doi:10.1136/ard.2008.092163 [PubMed 18684744]Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]"Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics Committee on Drugs. Pediatrics. 1997;99(2):268-278. [PubMed 9024461]James ER. The etiology of steroid cataract. J Ocul Pharmacol Ther. 2007;23(5):403-420. doi:10.1089/jop.2006.0067 [PubMed 17900234]James HE, Madauss WC, Tibbs PA, McCloskey JJ, Bean JR. The effect of high dose dexamethasone in children with severe closed head injury. A preliminary report. Acta Neurochir (Wien). 1979;45(3-4):225-236. [PubMed 371348]Janes M, Kuster S, Goldson TM, Forjuoh SN. Steroid-induced psychosis. Proc (Bayl Univ Med Cent). 2019;32(4):614-615. doi:10.1080/08998280.2019.1629223 [PubMed 31656440]Jordan K, Roila F, Molassiotis A, et al. Antiemetics in Children Receiving Chemotherapy. MASCC/ESMO Guideline Update 2009. Support Care Cancer. 2011;19(suppl 1):S37-S42. doi: 10.1007/s00520-010-0994-7. [PubMed 20824481]Joseph RM, Hunter AL, Ray DW, Dixon WG. Systemic glucocorticoid therapy and adrenal insufficiency in adults: a systematic review. Semin Arthritis Rheum. 2016;46(1):133-141. doi: 10.1016/j.semarthrit.2016.03.001. [PubMed 27105755]Joshi GP. Anesthetic management for enhanced recovery after major surgery (ERAS) in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 31, 2022.Kale Y, Aydemir O, Ceylan O, Bas AY, Demirel N. Hypertrophic cardiomyopathy after a single dose of dexamethasone in a preterm infant. Pediatr Neonatol. 2015;56(4):268-270. doi:10.1016/j.pedneo.2013.03.015 [PubMed 23639746]Kawai S, Ichikawa Y, Homma M. Differences in metabolic properties among cortisol, prednisolone, and dexamethasone in liver and renal diseases: accelerated metabolism of dexamethasone in renal failure. J Clin Endocrinol Metab. 1985;60(5):848-854. doi:10.1210/jcem-60-5-848 [PubMed 3980669]Keeney GE, Gray MP, Morrison AK, et al. Dexamethasone for acute asthma exacerbations in children: a meta-analysis. Pediatrics. 2014;133(3):493-499. [PubMed 24515516]Khemani RG, Randolph A, Markovitz B. Corticosteroids for the prevention and treatment of post-extubation stridor in neonates, Children and Adults. Cochrane Database Syst Rev. 2009;(3):CD001000. [PubMed 19588321]Klöti J, Fanconi S, Zachmann M, Zaugg H. Dexamethasone therapy and cortisol excretion in severe pediatric head injury. Childs Nerv Syst. 1987;3(2):103-105. [PubMed 3304622]Komatsu Y, Okita K, Yuki S, et al. Open-label, randomized, comparative, phase III study on effects of reducing steroid use in combination with palonosetron. Cancer Sci. 2015;106(7):891-895. doi:10.1111/cas.12675 [PubMed 25872578]Kowal-Bielecka O, Fransen J, Avouac J, et al; EUSTAR Coauthors. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis. 2017;76(8):1327-1339. doi:10.1136/annrheumdis-2016-209909. [PubMed 27941129]Kravitz J, Dominici P, Ufberg J, Fisher J, Giraldo P. Two days of dexamethasone versus 5 days of prednisone in the treatment of acute asthma: a randomized controlled trial [published correction appears in: Ann Emerg Med. 2018;71(1):9]. Ann Emerg Med. 2011;58(2):200-204. doi:10.1016/j.annemergmed.2011.01.004. [PubMed 21334098]Kretschmer H. Prognosis of severe head injuries in childhood and adolescence. Neuropediatrics. 1983;14(3):176-181. [PubMed 6621810]Kühne T, Freedman J, Semple JW, Doyle J, Butchart S, Blanchette VS. Platelet and immune responses to oral cyclic dexamethasone therapy in childhood chronic immune thrombocytopenic purpura. J Pediatr. 1997;130(1):17-24. [PubMed 9003846]Kumar A, Weber MH, Gokaslan Z, et al. Metastatic spinal cord compression and steroid treatment: a systematic review. Clin Spine Surg. 2017;30(4):156-163. doi:10.1097/BSD.0000000000000528. [PubMed 28437329]Lam DS, Fan DS, Ng JS, Yu CB, Wong CY, Cheung AYl. Ocular hypertensive and anti-inflammatory responses to different dosages of topical dexamethasone in children: a randomized trial. Clin Experiment Ophthalmol. 2005;33(3):252-258. [PubMed 15932528]Lamiable D, Vistelle R, Sulmont V, Millart H, Caron J, Choisy H. Pharmacocinétique de la dexaméthasone par voie orale chez le sujet obèse [pharmaco*kinetics of dexamethasone administered orally in obese patients]. Therapie. 1990;45(4):311-314. [PubMed 2399513]Larocca A, Bonello F, Gaidano G, et al. Dose/schedule-adjusted Rd-R vs continuous Rd for elderly, intermediate-fit patients with newly diagnosed multiple myeloma. Blood. 2021;137(22):3027-3036. doi:10.1182/blood.2020009507 [PubMed 33739404]Laubach JP. Multiple myeloma: administrations considerations for common therapies. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 9, 2022.Leachman SA, Reed BR. The use of dermatologic drugs in pregnancy and lactation. Dermatol Clin. 2006;24(2):167-197. [PubMed 16677965]Lee MJ, Guinn D. Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 23, 2021.Leonard JM. Central nervous system tuberculosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 9, 2019.Leonard MB. Glucocorticoid-induced osteoporosis in children: impact of the underlying disease. Pediatrics. 2007;119(suppl 2):S166-S174. [PubMed 17332238]Liu D, Ahmet A, Ward L, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013;9(1):30. doi:10.1186/1710-1492-9-30 [PubMed 23947590]Loblaw DA, Mitera G, Ford M, Laperriere NJ. A 2011 updated systematic review and clinical practice guideline for the management of malignant extradural spinal cord compression. Int J Radiat Oncol Biol Phys. 2012;84(2):312-317. doi:10.1016/j.ijrobp.2012.01.014. [PubMed 22420969]Lonial S, Dimopoulos M, Palumbo A, et al; ELOQUENT-2 Investigators. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373(7):621-631. [PubMed 26035255]Loprinzi CL, Kugler JW, Sloan JA, et al. Randomized comparison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia/cachexia. J Clin Oncol. 1999;17(10):3299-3306. doi:10.1200/JCO.1999.17.10.3299 [PubMed 10506633]Luger A, Broersen LHA, Biermasz NR, et al. ESE clinical practice guideline on functioning and nonfunctioning pituitary adenomas in pregnancy. Eur J Endocrinol. 2021;185(3):G1-G33. doi:10.1530/EJE-21-0462 [PubMed 34425558]Luks AM, Auerbach PS, Freer L, et al. Wilderness Medical Society clinical practice guidelines for the prevention and treatment of acute altitude illness: 2019 update. Wilderness Environ Med. 2019;30(4S):S3-S18. [PubMed 31248818]Luks AM, McIntosh SE, Grissom CK, et al. Wilderness Medical Society consensus guidelines for the prevention and treatment of acute altitude illness. Wilderness Environ Med. 2010;21(2):146-155. [PubMed 20591379]Luks AM, McIntosh SE, Grissom CK, et al. Wilderness Medical Society practice guidelines for the prevention and treatment of acute altitude illness: 2014 update. Wilderness Environ Med. 2014;25(4)(suppl):S4-S14. doi:10.1016/j.wem.2014.06.017. [PubMed 25498261]Lunghi L, Pavan B, Biondi C, et al. Use of Glucocorticoids in Pregnancy. Curr Pharm Des. 2010;16(32):3616-3637. [PubMed 20977425]Makol A, Wright K, Amin S. Rheumatoid arthritis and pregnancy: safety considerations in pharmacological management. Drugs. 2011;71(15):1973‐1987. doi:10.2165/11596240-000000000-00000 [PubMed 21985166]Malbari F, Staggers KA, Minard CG, Weiner HL, Chintagumpala MM, Levy AS. Provider views on perioperative steroid use for patients with newly diagnosed pediatric brain tumors. J Neurooncol. 2020;147(1):205-212. [PubMed 32026434]Mathes BM, Alquire PC. Intralesional corticosteroid injection. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 18, 2019.Mazzucconi MG, Fazi P, Bernasconi S, et al. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood. 2007;109(4):1401-1407. [PubMed 17077333]McCallister A, So TY, Stewart J. Evaluation of the efficacy of a onetime injectable dexamethasone administered orally in the pediatric emergency department for asthma exacerbation. J Pediatr Pharmacol Ther. 2017;22(5):326-331. [PubMed 29042832]McDonnell M, Evans N. Upper and Lower Gastrointestinal Complications With Dexamethasone Despite H2 Antagonists. J Paediatr Child Health. 1995;31(2):152-154. [PubMed 7794619]McGoldrick E, Stewart F, Parker R, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2020;12(12):CD004454. doi:10.1002/14651858.CD004454.pub4 [PubMed 33368142]McIntosh JJ. Corticosteroid guidance for pregnancy during COVID-19 pandemic [published online April 9, 2020]. Am J Perinatol. 2020. doi:10.1055/s-0040-1709684 [PubMed 32274772]Migita K, Sasaki Y, Ishizuka N, et al. Glucocorticoid therapy and the risk of infection in patients with newly diagnosed autoimmune disease. Medicine (Baltimore). 2013;92(5):285-293. doi:10.1097/MD.0b013e3182a72299 [PubMed 23982055]Mikhael J, Ismaila N, Cheung MC, et al. Treatment of multiple myeloma: ASCO and CCO joint clinical practice guideline. J Clin Oncol. 2019;37(14):1228-1263. doi:10.1200/JCO.18.02096 [PubMed 30932732]Miyabo S, Nakamura T, Kuwazima S, Kishida S. A comparison of the bioavailability and potency of dexamethasone phosphate and sulphate in man. Eur J Clin Pharmacol. 1981;20(4):277-282. [PubMed 6273180]Mongelluzzo J, Mohamad Z, Ten Have TR, et al. Corticosteroids and Mortality in Children With Bacterial Meningitis. JAMA. 2008;299(17):2048-2055. [PubMed 18460665]Moreau P, Dimopoulos MA, Mikhael J, et al; IKEMA Study Group. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Lancet. 2021;397(10292):2361-2371. doi:10.1016/S0140-6736(21)00592-4 [PubMed 34097854]Moreau P, Masszi T, Grzasko N, et al; TOURMALINE-MM1 Study Group. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;374(17):1621-1634. doi:10.1056/NEJMoa1516282 [PubMed 27119237]Moreau P, Mateos MV, Berenson JR, et al. Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study [published correction appears in Lancet Oncol. 2018;19(8):e382]. Lancet Oncol. 2018;19(7):953-964. doi:10.1016/S1470-2045(18)30354-1. [PubMed 29866475]Murphy VE, Fittock RJ, Zarzycki PK, et al. Metabolism of Synthetic Steroids by the Human Placenta. Placenta. 2007;28(1):39-46. [PubMed 16549198]Narayanaswami P, Sanders DB, Wolfe G, et al. International consensus guidance for management of myasthenia gravis: 2020 update. Neurology. 2021;96(3):114-122. doi:10.1212/WNL.0000000000011124 [PubMed 33144515]Narum S, Westergren T, Klemp M. Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis. BMJ Open. 2014;4(5):e004587. doi:10.1136/bmjopen-2013-004587 [PubMed 24833682]National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. NIH Publication No. 08-4051. Bethesda, MD: US Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute; 2007. http://www.nhlbi.nih.gov/files/docs/guidelines/asthgdln.pdf.National Collaborating Centre for Cancer (UK). Metastatic Spinal Cord Compression: Diagnosis and Management of Patients at Risk of or with Metastatic Spinal Cord Compression. Cardiff (UK): National Collaborating Centre for Cancer (UK); November 2008. (NICE Clinical Guidelines, No. 75.) https://www.ncbi.nlm.nih.gov/books/NBK55007/. Accessed September 19, 2019. [PubMed 22171401]National Institutes of Health (NIH). Coronavirus disease (COVID-19) treatment guidelines. https://www.covid19treatmentguidelines.nih.gov. Updated September 26, 2022. Accessed September 29, 2022.Neff SPW, Stapelberg F, Warmington A. Excruciating perineal pain after intravenous dexamethasone. Anaesth Intensive Care. 2002;30(3):370-371. [PubMed 12075649]Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA; American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190-4207. [PubMed 21325604]Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829-3866. doi:10.1182/bloodadvances.2019000966 [PubMed 31794604]Ng PC. The effectiveness and side effects of dexamethasone in preterm infants with bronchopulmonary dysplasia. Arch Dis Child. 1993;68(3)(spec no):330-336. [PubMed 8466274]Nguyen TH, Tran TH, Thwaites G, et al. Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis. N Engl J Med. 2007;357(24):2431-2440. doi:10.1056/NEJMoa070852. [PubMed 18077808]Nicolaides NC, Pavlaki AN, Maria Alexandra MA, Chrousos GP. Glucocorticoid therapy and adrenal suppression. In: Feingold KR, Anawalt B, Boyce A, et al, eds. Endotext. MDText.com, Inc; October 19, 2018. [PubMed 25905379]Nieman LK. Treatment of adrenal insufficiency in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 14, 2020.Nieman LK, Biller BM, Findling JW, et al. The diagnosis of Cushing's syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2008;93(5):1526-1540. [PubMed 18334580]O'Connell MB, Fritsch MA. Musculoskeletal and connective tissue disorders. Fundamentals of Geriatric Pharmacotherapy, 2nd ed. Hutchison LC, Sleeper RB, Eds. ASHP Publications, 2015.Onland W, Offringa M, De Jaegere AP, et al. Finding the optimal postnatal dexamethasone regimen for preterm infants at risk of bronchopulmonary dysplasia: a systematic review of placebo-controlled trials. Pediatrics. 2009;123(1):367-377. [PubMed 19117904]Orr SL, Friedman BW, Christie S, et al. Management of adults with acute migraine in the emergency department: the American Headache Society evidence assessment of parenteral pharmacotherapies. Headache. 2016;56(6):911-940. doi:10.1111/head.12835 [PubMed 27300483]Ost L, Wettrell G, Bjorkhem I, et al. Prednisolone excretion in human milk. J Pediatr. 1985;106(6):1008-1011. [PubMed 3998938]Oxford University News Release. Low-cost dexamethasone reduces death by up to one third in hospitalised patients with severe respiratory complications of COVID-19. Accessed on June 18, 2020. https://www.recoverytrial.net/files/recovery_dexamethasone_statement_160620_v2final.pdf.Palumbo A, Chanan-Khan A, Weisel K, et al; CASTOR Investigators. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(8):754-766. [PubMed 27557302]Park-Wyllie L, Mazzotta P, Pastuszak A, et al. Birth defects After Maternal Exposure to Corticosteroids: Prospective Cohort Study and Meta-Analysis of Epidemiological Studies. Teratology. 2000;62(6):385-392. [PubMed 11091360]Parsons S, Tran VL. The trilogy of SARS-CoV-2 in pediatrics (part 1): acute COVID-19 in special populations. J Pediatr Pharmacol Ther. 2021;26(3):220-239. doi:10.5863/1551-6776-26.3.220 [PubMed 33833623]Pastores SM, Annane D, Rochwerg B; Corticosteroid Guideline Task Force of SCCM and ESICM. Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part II): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017. Intensive Care Med. 2018;44(4):474-477. [PubMed 29090327]Patel P, Olteanu A, Cabral S, Santesso N, Robinson PD, Dupuis LL. Dexamethasone dosing for prevention of acute chemotherapy-induced vomiting in pediatric patients: A systematic review. Pediatr Blood Cancer. 2020;67(12):e28716. doi:10.1002/pbc.28716. [PubMed 32970373]Patel P, Robinson PD, Thackray J, et al. Guideline for the prevention of acute chemotherapy-induced nausea and vomiting in pediatric cancer patients: a focused update. Pediatr Blood Cancer. 2017;64(10). doi:10.1002/pbc.26542. [PubMed 28453189]Patt H, Bandgar T, Lila A, Shah N. Management issues with exogenous steroid therapy. Indian J Endocrinol Metab. 2013;17(suppl 3):S612-S617. doi:10.4103/2230-8210.123548 [PubMed 24910822]Pelewicz K, Miśkiewicz P. Glucocorticoid withdrawal—an overview on when and how to diagnose adrenal insufficiency in clinical practice. Diagnostics (Basel). 2021;11(4):728. doi:10.3390/diagnostics11040728 [PubMed 33923971]Pereira RM, Freire de Carvalho J. Glucocorticoid-induced myopathy. Joint Bone Spine. 2011;78(1):41-44. doi:10.1016/j.jbspin.2010.02.025 [PubMed 20471889]Perron G, Dolbec P, Germain J, Béchard P. Perineal pruritus after i.v. dexamethasone administration. Can J Anaesth. 2003;50(7):749-750. [PubMed 12944454]Petrocheilou A, Tanou K, Kalampouka E, Malakasioti G, Giannios C, Kaditis AG. Viral croup: diagnosis and a treatment algorithm. Pediatr Pulmonol. 2014;49(5):421-429. [PubMed 24596395]Phillips RS, Gopaul S, Gibson F, et al. Antiemetic Medication for Prevention and Treatment of Chemotherapy Induced Nausea and Vomiting in Childhood. Cochrane Database Syst Rev. 2010;(9):CD007786. [PubMed 20824866]Phulke S, Kaushik S, Kaur S, Pandav SS. Steroid-induced glaucoma: An avoidable irreversible blindness. J Curr Glaucoma Pract. 2017;11(2):67-72. doi:10.5005/jp-journals-l0028-1226 [PubMed 28924342]Pilkey J, Streeter L, Beel A, Hiebert T, Li X. Corticosteroid-induced diabetes in palliative care. J Palliat Med. 2012;15(6):681-689. doi:10.1089/jpm.2011.0513 [PubMed 22583383]Pivonello R, Isidori AM, De Martino MC, Newell-Price J, Biller BM, Colao A. Complications of Cushing's syndrome: state of the art. Lancet Diabetes Endocrinol. 2016;4(7):611-629. doi:10.1016/S2213-8587(16)00086-3 [PubMed 27177728]Pollard AJ, Niermeyer S, Barry P, et al. Children at high altitude: An international consensus statement by an ad hoc committee of the International Society for Mountain Medicine, March 12, 2001. High Alt Med Biol. 2001;2(3):389-403. [PubMed 11682018]Poon LC, Yang H, Kapur A, et al. Global interim guidance on coronavirus disease 2019 (COVID-19) during pregnancy and puerperium from FIGO and allied partners: Information for healthcare professionals. Int J Gynaecol Obstet. 2020;149(3):273-286. doi:10.1002/ijgo.13156 [PubMed 32248521]Portenoy RK, Ahmed E, Keilson YY. Cancer pain management: role of adjuvant analgesics (coanalgesics). Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 6, 2022. [PubMed 32248521]Pradat P, Robert-Gnansia E, Di Tanna GL, et al. First trimester exposure to corticosteroids and oral clefts. Birth Defects Res A Clin Mol Teratol. 2003;67(12):968-970. [PubMed 14745915]Prete A, Bancos I. Glucocorticoid induced adrenal insufficiency. BMJ. 2021;374:n1380. doi:10.1136/bmj.n1380 [PubMed 34253540]Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019;3(22):3780-3817. doi:10.1182/bloodadvances.2019000812 [PubMed 31770441]Qureshi F, Zaritsky A, Poirier MP. Comparative efficacy of oral dexamethasone versus oral prednisone in acute pediatric asthma. J Pediatr. 2001;139(1):20-26. [PubMed 11445789]Raajasekar AKA, Barola S, Tehrani L, Chandra AB. To push or not to push: the benefit of administering anti-emetics by intravenous push. Blood. 2015;126(23):3314. https://ashpublications.org/blood/article/126/23/3314/90789/To-Push-or-Not-to-Push-The-Benefit-of.Rajkumar SV. Multiple myeloma: 2011 update on diagnosis, risk-stratification, and management [published correction appears in Am J Hematol. 2014;89(6):669]. Am J Hematol. 2011;86(1):57-65. doi:10.1002/ajh.21913. [PubMed 21181954]Rajkumar SV, Jacobus S, Callander NS, et al; Eastern Cooperative Oncology Group. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2010;11(1):29-37. doi:10.1016/S1470-2045(09)70284-0. [PubMed 19853510]Razeghinejad MR, Katz LJ. Steroid-induced iatrogenic glaucoma. Ophthalmic Res. 2012;47(2):66-80. doi:10.1159/000328630 [PubMed 21757964]RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in hospitalized patients with covid-19 - preliminary report. N Engl J Med. Published online July 17, 2020. doi:10.1056/NEJMoa2021436 [PubMed 32678530]Rehrer MW, Liu B, Rodriguez M, Lam J, Alter HJ. A randomized controlled noninferiority trial of single dose of oral dexamethasone versus 5 days of oral prednisone in acute adult asthma. Ann Emerg Med. 2016;68(5):608-613. doi:10.1016/j.annemergmed.2016.03.017 [PubMed 27117874]Richter O, Ern B, Reinhardt D, Becker B. Pharmaco*kinetics of dexamethasone in children. Pediatr Pharmacol (New York). 1983;3(3-4):329-337. [PubMed 6677878]Rittichier KK, Ledwith CA. Outpatient Treatment of Moderate Croup With Dexamethasone: Intramuscular Versus Oral Dosing. Pediatrics. 2000;106(6):1344-1348. [PubMed 11099587]Roberts WN. Intraarticular and soft tissue injections: What agent(s) to inject and how frequently? Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 26, 2019.Roeland EJ, Bohlke K, Baracos VE, et al. Management of cancer cachexia: ASCO guideline. J Clin Oncol. 2020;38(21):2438-2453. doi:10.1200/JCO.20.00611 [PubMed 32432946]Rohdewald P, Möllmann H, Barth J, Rehder J, Derendorf H. Pharmaco*kinetics of dexamethasone and its phosphate ester. Biopharm Drug Dispos. 1987;8(3):205-212. [PubMed 3593899]Roila F, Molassiotis A, Herrstedt J, et al. 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Ann Oncol. 2016;27(suppl 5):v119-v133. [PubMed 27664248]Rosiñol L, Oriol A, Rios R, et al. Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplant in multiple myeloma. Blood. 2019;134(16):1337-1345. doi:10.1182/blood.2019000241 [PubMed 31484647]Roth P, Happold C, Weller M. Corticosteroid use in neuro-oncology: an update. Neurooncol Pract. 2015;2(1):6-12. doi:10.1093/nop/npu029 [PubMed 26034636]Rottenstreich A, Wexler ID, Abu-Libdeh A, Berkun Y. Iatrogenic cushing syndrome due to intranasal dexamethasone. Clin Pediatr (Phila). 2015;54(12):1215-1257. doi:10.1177/0009922814563927 [PubMed 25533884]Roxanas MG, Hunt GE. Rapid reversal of corticosteroid-induced mania with sodium valproate: a case series of 20 patients. Psychosomatics. 2012;53(6):575-581. doi:10.1016/j.psym.2012.06.006 [PubMed 23157995]Russell KF, Liang Y, O'Gorman K, Johnson DW, Klassen TP. Glucocorticoids for croup. Cochrane Database Syst Rev. 2011;(1):CD001955. [PubMed 21249651]Russell K, Wiebe N, Saenz A, et al. Glucocorticoids for Croup. Cochrane Database Syst Rev. 2004;(1):CD001955. [PubMed 14973975]Ryken TC, McDermott M, Robinson PD, et al. The role of steroids in the management of brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol. 2010;96(1):103-114. doi:10.1007/s11060-009-0057-4 [PubMed 19957014]Saad AF, Chappell L, Saade GR, Pacheco LD. Corticosteroids in the management of pregnant patients with coronavirus disease (COVID-19). Obstet Gynecol. 2020;136(4):823-826. doi:10.1097/AOG.0000000000004103 [PubMed 32769659]Salem M, Tainsh RE Jr, Bromberg J, Loriaux DL, Chernow B. Perioperative glucocorticoid coverage. A reassessment 42 years after emergence of a problem. Ann Surg. 1994;219(4):416-425. doi:10.1097/00000658-199404000-00013 [PubMed 8161268]Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol. 2020;72(4):529‐556. doi:10.1002/art.41191 [PubMed 32090480]San Miguel J, Weisel K, Moreau P, et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14(11):1055-1066. doi:10.1016/S1470-2045(13)70380-2 [PubMed 24007748]Sexton DJ. Dexamethasone to prevent neurologic complications of bacterial meningitis in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com.Accessed September 20, 2019.Shefrin AE, Goldman RD. Use of dexamethasone and prednisone in acute asthma exacerbations in pediatric patients. Can Fam Physician. 2009;55(7):704-706. [PubMed 19602654]Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259. [PubMed 19188870]Shenoi RP, Timm N; Committee on Drugs; Committee on Pediatric Emergency Medicine. Drugs used to treat pediatric emergencies. Pediatrics. 2020;145(1):e20193450. [PubMed 31871244]Siegel MD, Siemieniuk R. Acute respiratory distress syndrome: Supportive care and oxygenation in adults. Post TW, ed. UpToDate. http://www.uptodate.com. Waltham, MA: UpToDate Inc. Accessed July 17, 2020.Singh A, Alter HJ, Zaia B. Does the addition of dexamethasone to standard therapy for acute migraine headache decrease the incidence of recurrent headache for patients treated in the emergency department? A meta-analysis and systematic review of the literature. Acad Emerg Med. 2008;15(12):1223-1233. doi:10.1111/j.1553-2712.2008.00283.x [PubMed 18976336]Singh M, Sharma CS, Rautela RS, Taneja A. Intravenous dexamethasone causes perineal pain and pruritus. J Anesthe Clinic Res. 2011;4:273. doi:10.4172/2155-6148.1000273 http://www.omicsonline.org/intravenous-dexamethasone-causes-perineal-pain-and-pruritus-2155-6148.1000273.pdf .Society for Maternal Fetal Medicine (SMFM) and the Society for Obstetric Anesthesia and Perinatology (SOAP). Revise Labor and Delivery COVID-19 Considerations (April 14, 2020; updated from an earlier version on March 27, 2020). Accessed April 17, 2020. https://www.smfm.org/covidclinical.Sonneveld P, Schmidt-Wolf IG, van der Holt B, et al. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012;30(24):2946-2955. doi:10.1200/JCO.2011.39.6820 [PubMed 22802322]Sparrow A, Geelhoed G. Prednisolone Versus Dexamethasone in Croup: A Randomised Equivalence Trial. Arch Dis Child. 2006;91(7):580-583. [PubMed 16624882]Speiser PW, Arlt W, Auchus RJ, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(11):4043-4088. doi:10.1210/jc.2018-01865 [PubMed 30272171]Speiser PW, Azziz R, Baskin LS, et al; Endocrine Society. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline [published correction appear in J Clin Endocrinol Metab. 2010;95(11):5137]. J Clin Endocrinol Metab. 2010;95(9):4133-4160. doi:10.1210/jc.2009-2631 [PubMed 20823466]Stark AR, Carlo WA, Tyson JE, et al; National Institute of Child Health and Human Development Neonatal Research Network. Adverse effects of early dexamethasone treatment in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med. 2001;344(2):95-101. doi:10.1056/NEJM200101113440203 [PubMed 11150359]Steen VD, Medsger TA Jr. Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis. Arthritis Rheum. 1998;41(9):1613-1619. doi:10.1002/1529-0131(199809)41:9<1613::AID-ART11>3.0.CO;2-O [PubMed 9751093]Sterne JAC, Murthy S, Diaz, JV; et al. World Health Organization (WHO) Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA. Published online September 2, 2020. doi:10.1001/jama.2020.17023 [PubMed 32876694]Stewart AK, Rajkumar SV, Dimopoulos MA, et al; ASPIRE Investigators. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372(2):142-152. doi:10.1056/NEJMoa1411321. [PubMed 25482145]Sturdza A, Millar BA, Bana N, et al. The use and toxicity of steroids in the management of patients with brain metastases. Support Care Cancer. 2008;16(9):1041-1048. doi:10.1007/s00520-007-0395-8 [PubMed 18256860]Tamez-Pérez HE, Quintanilla-Flores DL, Rodríguez-Gutiérrez R, González-González JG, Tamez-Peña AL. Steroid hyperglycemia: Prevalence, early detection and therapeutic recommendations: A narrative review. World J Diabetes. 2015;6(8):1073-1081. doi:10.4239/wjd.v6.i8.1073 [PubMed 26240704]TaperDex (dexamethasone) [prescribing information]. Ridgeland, MS: Xspire Pharma; February 2020.Tellez DW, Galvis AG, Storgion SA, et al. Dexamethasone in the Prevention of Postextubation Stridor in Children. J Pediatr. 1991;118(2):289-294. [PubMed 1993963]Thwaites GE, Nguyen DB, Nguyen HD, et al. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. N Engl J Med. 2004;351(17):1741-1751. [PubMed 15496623]Tóth GG, Kloosterman C, Uges DR, Jonkman MF. Pharmaco*kinetics of high-dose oral and intravenous dexamethasone. Ther Drug Monit. 1999;21(5):532-535. [PubMed 10519450]Trang G, Steele R, Baron M, Hudson M. Corticosteroids and the risk of scleroderma renal crisis: a systematic review. Rheumatol Int. 2012;32(3):645-653. doi:10.1007/s00296-010-1697-6 [PubMed 21132302]Tseng CL, Chen YT, Huang CJ, et al. Short-term use of glucocorticoids and risk of peptic ulcer bleeding: a nationwide population-based case-crossover study. Aliment Pharmacol Ther. 2015;42(5):599-606. doi:10.1111/apt.13298 [PubMed 26096497]Tuca A, Jimenez-Fonseca P, Gascón P. Clinical evaluation and optimal management of cancer cachexia. Crit Rev Oncol Hematol. 2013;88(3):625-636. doi:10.1016/j.critrevonc.2013.07.015 [PubMed 23953794]Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39(9):1267-1284. [PubMed 15494903]University of Oxford. RECOVERY Trial. Accessed July 8, 2020. https://www.recoverytrial.net/.Urban RC Jr, Cotlier E. Corticosteroid-induced cataracts. Surv Ophthalmol. 1986;31(2):102-110. doi:10.1016/0039-6257(86)90077-9 [PubMed 3541262]US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Updated March 2019. Accessed April 8, 2019. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf.van Staa TP, Cooper C, Leufkens HG, Bishop N. Children and the risk of fractures caused by oral corticosteroids. J Bone Miner Res. 2003;18(5):913-918. doi:10.1359/jbmr.2003.18.5.913 [PubMed 12733732]van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int. 2002;13(10):777-787. doi:10.1007/s001980200108 [PubMed 12378366]Vecht CJ, Hovestadt A, Verbiest HB, van Vliet JJ, van Putten WL. Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain tumors: a randomized study of doses of 4, 8, and 16 mg per day. Neurology. 1994;44(4):675-680. doi:10.1212/wnl.44.4.675 [PubMed 8164824]Villar J, Ferrando C, Martínez D, et al; dexamethasone in ARDS network. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med. 2020;8(3):267-276. doi:10.1016/S2213-2600(19)30417-5 [PubMed 32043986]Wald ER, Kaplan SL, Mason, EO Jr. Dexamethasone therapy for children with bacterial meningitis. Pediatrics. 1995;95(1):21-28. [PubMed 7770303]Wallace MD, Metzger NL. Optimizing the treatment of steroid-induced hyperglycemia. Ann Pharmacother. 2018;52(1):86-90. doi:10.1177/1060028017728297 [PubMed 28836444]Wang JJ, Ho ST, Lee SC, Liu YC, Ho CM. The use of dexamethasone for preventing postoperative nausea and vomiting in females undergoing thyroidectomy: a dose-ranging study. Anesth Analg. 2000a;91(6):1404-1407. doi:10.1097/00000539-200012000-00019 [PubMed 11093989]Wang JJ, Ho ST, Tzeng JI, Tang CS. The effect of timing of dexamethasone administration on its efficacy as a prophylactic antiemetic for postoperative nausea and vomiting. Anesth Analg. 2000b;91(1):136-139. doi:10.1097/00000539-200007000-00025 [PubMed 10866900]Warrington TP, Bostwick JM. Psychiatric adverse effects of corticosteroids. Mayo Clin Proc. 2006;81(10):1361-1367. doi:10.4065/81.10.1361 [PubMed 17036562]Watterberg KL; American Academy of Pediatrics. Committee on Fetus and Newborn. Policy Statement--Postnatal Corticosteroids to Prevent or Treat Bronchopulmonary Dysplasia. Pediatrics. 2010;126(4):800-808. [PubMed 20819899]Wei Y, Ji XB, Wang YW, et al. High-dose dexamethasone vs prednisone for treatment of adult immune thrombocytopenia: a prospective multicenter randomized trial. Blood. 2016;127(3):296-302. [PubMed 26480931]Widdifield J, Bernatsky S, Paterson JM, et al. Serious infections in a population-based cohort of 86,039 seniors with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2013;65(3):353-361. doi:10.1002/acr.21812 [PubMed 22833532]Winthrop KL. Infections and biologic therapy in rheumatoid arthritis: our changing understanding of risk and prevention. Rheum Dis Clin North Am. 2012;38(4):727-745. doi:10.1016/j.rdc.2012.08.019 23137579. [PubMed 23137579]World Health Organization (WHO). Breastfeeding and maternal medication, recommendations for drugs in the eleventh WHO model list of essential drugs. 2002. https://apps.who.int/iris/handle/10665/62435.World Health Organization (WHO). Corticosteroids for COVID-19: living guidance. Published September 2, 2020. Accessed September 4, 2020. https://www.who.int/publications/i/item/WHO-2019-nCoV-Corticosteroids-2020.1World Health Organization (WHO). Guidelines for treatment of drug-susceptible tuberculosis and patient care: 2017 update. Published 2017. Accessed April 9, 2019. https://apps.who.int/iris/bitstream/handle/10665/255052/9789241550000-eng.pdf;jsessionid=DE537F54942A5274CE53BA18E0FBCC15?sequence=1Yale SH, Limper AH. Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illness and prior corticosteroid therapy. Mayo Clin Proc. 1996;71(1):5-13. doi:10.4065/71.1.5 [PubMed 8538233]Yanovski JA, Cutler GB Jr, Chrousos GP, Nieman LK. Corticotropin-releasing hormone stimulation following low-dose dexamethasone administration. A new test to distinguish Cushing's syndrome from pseudo-Cushing's states. JAMA. 1993;269(17):2232-2238. [PubMed 8386285]Yildirim ZK, Büyükavci M, Eren S, Orbak Z, Sahin A, Karakelleoğlu C. Late side effects of high-dose steroid therapy on skeletal system in children with idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol. 2008;30(10):749-753. doi:10.1097/MPH.0b013e318180bbc9 [PubMed 19011472]Younes AK, Younes NK. Recovery of steroid induced adrenal insufficiency. Transl Pediatr. 2017;6(4):269-273. doi:10.21037/tp.2017.10.01 [PubMed 29184808]Youssef J, Novosad SA, Winthrop KL. Infection risk and safety of corticosteroid use. Rheum Dis Clin North Am. 2016;42(1):157-176, ix-x. doi:10.1016/j.rdc.2015.08.004 [PubMed 26611557]Zar T, Graeber C, Perazella MA. Recognition, treatment, and prevention of propylene glycol toxicity. Semin Dial. 2007;20(3):217-219. [PubMed 17555487]Topic 9100 Version 680.0

CloseDexamethasone (systemic): Pediatric drug informationDexamethasone (systemic): Pediatric drug information(For additional information see "Dexamethasone (systemic): Drug information" and see "Dexamethasone (systemic): Patient drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USActive Injection D [DSC];Decadron [DSC];Dexabliss;Dexamethasone Intensol;DexPak 10 Day [DSC];DexPak 13 Day [DSC];DexPak 6 Day [DSC];DoubleDex;Dxevo 11-Day;Hemady;HiDex 6-Day;MAS Care-Pak;ReadySharp Dexamethasone [DSC];TaperDex 12-Day;TaperDex 6-Day;TaperDex 7-Day;TopiDex;ZCORT 7-Day [DSC]Brand Names: CanadaAPO-Dexamethasone;Dexamethasone Omega Unidose;Dexamethasone-Omega;Odan-Dexamethasone;PMS-Dexamethasone;PMS-Dexamethasone Sod Phosphat [DSC];PRO-Dexamethasone-4 [DSC]Therapeutic CategoryAdrenal Corticosteroid;Anti-inflammatory Agent;Antiemetic;Corticosteroid, Systemic;GlucocorticoidDosing: NeonatalAirway edema or extubationAirway edema or extubation: Limited data available: IV: 0.25 mg/kg/dose given ~4 hours prior to scheduled extubation then every 8 hours for a total of 3 doses (Ref); others have used 0.5 mg/kg/dose every 8 hours for 3 doses with last dose administered 1 hour prior to scheduled extubation (Ref); range: 0.25 to 0.5 mg/kg/dose for 1 to 3 doses; maximum daily dose: 1.5 mg/kg/day. Note: A longer duration of therapy may be needed with more severe cases. A recent meta-analysis concluded that future neonatal clinical trials should study a multiple dose strategy with initiation of dexamethasone at least 12 hours before extubation (Ref).Bronchopulmonary dysplasia, facilitation of ventilator weanBronchopulmonary dysplasia, facilitation of ventilator wean: Limited data available: PNA ≥7 days: Oral, IV: Initial: 0.15 mg/kg/day in divided doses every 12 hours for 3 days, followed by a taper of: 0.1 mg/kg/day for 3 days, then 0.05 mg/kg/day for 2 days, and 0.02 mg/kg/day for 2 days for a total dexamethasone dose of 0.89 mg/kg given over 10 days; tapering doses were administered in divided doses every 12 hours (Ref). Note: Multiple regimens have been described. Optimal regimen has not been defined. High doses (~0.5 mg/kg/day) are associated with higher incidence of adverse effects (including adverse neurodevelopmental outcomes) and are not recommended for use (Ref). However, a meta-analysis reported total cumulative doses >4 mg/kg initiated after the first week of life produced a greater reduction in the relative risk compared to lower cumulative doses for the combined outcome, mortality, or bronchopulmonary dysplasia without increasing the risk of neurodevelopmental sequelae in ventilated preterm infants (Ref).Dosing: PediatricCOVID-19, treatmentCOVID-19, treatment: Very limited data available:Note: Safety and effectiveness of dexamethasone or other corticosteroids for COVID-19 treatment have not been sufficiently evaluated in pediatric patients; use is extrapolated from adult patients; use caution. Reserve use for hospitalized patients who require high-flow oxygen, noninvasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO); not routinely recommended for pediatric patients requiring low levels of oxygen support (ie, nasal canula only). Use in profoundly immunocompromised pediatric patients should be considered only on a case-by-case basis as it has not been evaluated and may be harmful. Pediatric patients with COVID-19 should be enrolled in clinical trials whenever possible (Ref).Infants, Children, and Adolescents: IV, Oral: 0.15 to 0.3 mg/kg/dose once daily for up to 10 days; maximum dose: 6 mg/dose (Ref). Note: An equivalent dose of an alternative glucocorticoid may be substituted if dexamethasone is unavailable (Ref).Acute mountain sickness/high altitude cerebral edema; treatmentAcute mountain sickness (AMS) (moderate)/high altitude cerebral edema (HACE); treatment: Limited data available: Note: Dexamethasone does not facilitate acclimatization; further ascent should be delayed until patient is asymptomatic off medication (Ref).Infants, Children, and Adolescents: Oral, IM, IV: 0.15 mg/kg/dose every 6 hours; maximum dose: 4 mg/dose (Ref).Airway edema or extubationAirway edema or extubation: Limited data available: Infants, Children, and Adolescents: Oral, IM, IV: 0.5 mg/kg/dose (maximum dose: 10 mg/dose) administered 6 to 12 hours prior to extubation then every 6 hours for 6 doses (total dexamethasone dose: 3 mg/kg) (Ref).Anti-inflammatoryAnti-inflammatory: Infants, Children, and Adolescents: Oral, IM, IV: Initial dose range: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day in divided doses every 6 to 12 hours; dose depends upon condition being treated and response of patient; dosage for infants and children should be based on disease severity and patient response; usual adult initial daily dose range: 0.75 to 9 mg/day.Asthma exacerbationAsthma exacerbation: Limited data available: Infants, Children, and Adolescents: Oral, IM, IV: 0.6 mg/kg once daily as a single dose or once daily for 2 days; maximum dose: 16 mg/dose (Ref); single dose regimens as low as 0.3 mg/kg/dose and as high as 1.7 mg/kg/dose have also been reported (Ref). Note:Duration >2 days is not recommended due to increased risk of metabolic effects (Ref).Bacterial meningitisBacterial meningitis (Haemophilus influenzae type b): Limited data available:Infants >6 weeks and Children: IV: 0.15 mg/kg/dose every 6 hours for the first 2 to 4 days of antibiotic treatment; start dexamethasone 10 to 20 minutes before or with the first dose of antibiotic; if antibiotics have already been administered, dexamethasone use has not been shown to improve patient outcome and is not recommended (Ref). Note: For pneumococcal meningitis, efficacy results are variable and use is controversial; risk and benefits should be considered prior to use (Ref).Cerebral edemaCerebral edema: Limited data available: Note: Dose, route, and duration may vary due to underlying cause of edema; tapering may be required. Infants, Children, and Adolescents: Oral, IM, IV: Loading dose: 1 to 2 mg/kg/dose as a single dose; maintenance: 1 to 2 mg/kg/day in divided doses every 4 to 6 hours; maximum daily dose: 16 mg/day (Ref).Chemotherapy-induced nausea and vomiting, preventionChemotherapy-induced nausea and vomiting, prevention: Reported regimens variable; optimal dose not established (Ref). Refer to individual protocols and emetogenic potential:Infants, Children, and Adolescents:POGO recommendations (Ref): Note: Reduce dose by 50% if administered concomitantly with aprepitant:Highly/severely emetogenic chemotherapy: Oral, IV: 6 mg/m2/dose every 6 hours.Moderately emetogenic chemotherapy: Oral, IV:BSA ≤0.6 m2: 2 mg every 12 hours.BSA >0.6 m2: 4 mg every 12 hours.Alternate dosing: Highly/severely emetogenic chemotherapy: IV: Usual: 10 mg/m2/dose once daily on days of chemotherapy; some patients may require every 12-hour dosing; usual range: 8 to 14 mg/m2/dose (Ref).Congenital adrenal hyperplasia, maintenanceCongenital adrenal hyperplasia, maintenance: Adolescents (fully grown): Oral: 0.25 to 0.5 mg once daily; use of a liquid dosage form may be preferable to allow for better dose titration (Ref). Note: For younger patients who are still growing, hydrocortisone or fludrocortisone are preferred.CroupCroup (laryngotracheobronchitis): Limited data available; dosing regimens variable:Infants and Children: Oral, IM, IV: 0.6 mg/kg once; reported maximum dose highly variable; usual maximum dose: 16 mg/dose (Ref); in trials, maximum doses of 10 to 20 mg/dose have been reported with similar efficacy findings for mild to moderate croup. The majority of reported experience in infants are those ≥3 months of age; data available in <3 months of age is very limited (Ref). In one evaluation of 22 children >2 years of age, a maximum dose of 12 mg/dose (at 0.6 mg/kg/dose) did not decrease endogenous glucocorticoid levels (Ref). A single oral dose of 0.15 mg/kg has also been shown effective in infants ≥3 months and children with mild to moderate croup (Ref).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricInfants, Children, and Adolescents: IM, IV, Oral:Kidney impairment: There are no dosage adjustments provided in the manufacturer's labeling; use with caution.Hemodialysis or peritoneal dialysis: Based on adult data, supplemental dose is not necessary (Ref).Dosing: Hepatic Impairment: PediatricInfants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling.Dosing: Adult(For additional information see "Dexamethasone (systemic): Drug information")Note: Dosing: Evidence to support an optimal dose and duration is lacking for most indications; recommendations provided are general guidelines only and primarily based on expert opinion. In general, glucocorticoid dosing should be individualized and the minimum effective dose/duration should be used. Hypothalamic-pituitary-adrenal (HPA) suppression: Although some patients may become hypothalamic-pituitary-adrenal (HPA) suppressed with lower doses or briefer exposure, some experts consider HPA-axis suppression likely in any adult receiving >3 mg/day (daytime dosing) or ≥0.75 mg per 24 hours (evening or night dosing) for >2 weeks or with Cushingoid appearance (Ref); do not abruptly discontinue treatment in these patients; dose tapering may be necessary (Ref).Usual dosage range:Oral, IV, IM: 4 to 20 mg/day given in a single daily dose or in 2 to 4 divided doses; High dose: 0.4 to 0.8 mg/kg/day (usually not to exceed 40 mg/day).Indication-specific dosing:Acute mountain sickness/high-altitude cerebral edemaAcute mountain sickness/high-altitude cerebral edema (off-label use):Prevention, moderate- to high-risk situations(alternative agent): Note: Use in addition to gradual ascent and start the day of ascent.Oral: 2 mg every 6 hours or 4 mg every 12 hours; may be discontinued after staying at the same elevation for 2 to 4 days or if descent is initiated. Due to adverse effects, limit duration to ≤10 days (Ref); some experts limit to ≤7 days (Ref). In situations of rapid ascent to altitudes >3,500 meters (eg, rescue or military operations), 4 mg every 6 hours may be considered (Ref).Treatment:Acute mountain sickness (moderate to severe): Note: Dexamethasone does not facilitate acclimatization; further ascent should be delayed until patient is asymptomatic off medication (Ref).Oral, IM, IV: 4 mg every 6 hours, continue until 24 hours after symptoms resolve or descent completed (not longer than 7 days total) (Ref).High-altitude cerebral edema: Oral, IM, IV: 8 mg as a single dose, followed by 4 mg every 6 hours until descent is complete and symptoms resolve (Ref).Acute respiratory distress syndrome, moderate to severeAcute respiratory distress syndrome, moderate to severe (off-label use): Note: May consider in most patients with persistent or refractory moderate to severe acute respiratory distress syndrome who are relatively early in the disease course (within 14 days) (Ref). Do not abruptly discontinue since this may cause deterioration due to inflammatory response (Ref).IV: 20 mg once daily from days 1 to 5, then 10 mg once daily from days 6 to 10 (Ref).Adrenal insufficiency, adrenal crisisAdrenal insufficiency, adrenal crisis (alternative agent): Note: Dexamethasone should only be used if hydrocortisone is unavailable. Corticosteroid therapy should be combined with adequate fluid resuscitation in patients with primary adrenal insufficiency (Ref).IV: 4 mg every 12 hours; transition to hydrocortisone as soon as possible (Ref).Adrenal insufficiency, primary chronicAdrenal insufficiency, primary chronic (alternative agent): Note: For use in patients who are unable to tolerate treatment with other glucocorticoids (hydrocortisone is preferred); risk of overreplacement may be higher with dexamethasone (Ref). Use in conjunction with fludrocortisone. Dose is based on prednisolone equivalency.Chronic maintenance dosing:Oral: Usual dosage range: 0.25 to 0.75 mg once daily (Ref).Stress dosing:Note: Patients who are unable to tolerate oral medication (eg, due to vomiting or diarrhea), are in active labor, or are under surgical stress may require parenteral corticosteroid therapy (preferably with hydrocortisone) to prevent adrenal crisis (Ref).Patients with febrile illness: Oral: Double the chronic maintenance dose until recovery for fever 38°C (100.4°F) to 39°C (102.2°F) or triple the chronic maintenance dose until recovery for fever >39°C (102.2°F), then return to baseline dose within 1 to 3 days (Ref).Minor surgical stress (eg, hernia repair, procedures with local anesthetic): Oral: Continue chronic maintenance dose (no additional supplementation needed) (Ref); may give an additional 0.75 mg (equivalent to ~20 mg hydrocortisone) postoperatively if signs or symptoms of adrenal insufficiency are present (Ref).Antiemetic regimens: Chemotherapy-associated nausea and vomiting, preventionAntiemetic regimens: Chemotherapy-associated nausea and vomiting, prevention (off-label use): Note: When dexamethasone is given with rolapitant in a prechemotherapy regimen, the oral route for both is generally used. When checkpoint inhibitor therapy is administered in combination with emetogenic chemotherapy, there is no evidence to omit dexamethasone from the prophylactic antiemetic regimen (Ref).Single-day IV chemotherapy regimens: Highly emetogenic chemotherapy (>90% risk of emesis): Cisplatin and other highly emetogenic single agents: Dexamethasone dose depends on specific neurokinin 1 (NK1) receptor antagonist: Day of chemotherapy: Administer prior to chemotherapy and in combination with an NK1 receptor antagonist, and a 5-HT3 receptor antagonist, with or without olanzapine (Ref).In combination with aprepitant, fosaprepitant, netupitant/palonosetron (NEPA), or fosnetupitant/palonosetron: Oral, IV: 12 mg.In combination with rolapitant: Oral, IV: 20 mg.If NK1 receptor antagonist not used: Oral, IV: 20 mg.Postchemotherapy days:If aprepitant given: Oral, IV: 8 mg once daily on days 2 to 4 (Ref).If fosaprepitant given: Oral, IV: 8 mg once on day 2, followed by 8 mg twice daily on days 3 and 4 (Ref).If NEPA or fosnetupitant/palonosetron given: Prophylaxis with dexamethasone on subsequent days is not needed unless regimen contained cisplatin: Oral, IV: 8 mg once daily on days 2 to 4 (Ref).If rolapitant given: Oral, IV: 8 mg twice daily on days 2 to 4 (Ref).If NK1 receptor antagonist not used: Oral, IV: 8 mg twice daily on days 2 to 4 (Ref).Highly emetogenic chemotherapy (>90% risk of emesis): Breast cancer regimens that include an anthracycline combined with cyclophosphamide:Dexamethasone dose depends on specific NK1 receptor antagonist: Day of chemotherapy: Administer prior to chemotherapy and in combination with an NK1 receptor antagonist, and a 5-HT3 receptor antagonist, with or without olanzapine (Ref).In combination with aprepitant, fosaprepitant, NEPA, fosnetupitant/palonosetron: Oral, IV: 12 mg (Ref).In combination with rolapitant: Oral, IV: 20 mg (Ref).If NK1 receptor antagonist not used: Oral, IV: 20 mg (Ref).Postchemotherapy days: Dexamethasone use is not recommended (an alternative agent or agents is/are recommended) (Ref).Moderately emetogenic chemotherapy (30% to 90% risk of emesis): Carboplatin-based regimens: Dexamethasone dose depends on specific NK1 receptor antagonist (Ref):Day of chemotherapy: Administer prior to chemotherapy and in combination with an NK1 receptor antagonist and a 5-HT3 receptor antagonist (Ref).In combination with aprepitant, fosaprepitant, NEPA, or fosnetupitant/palonosetron: Oral, IV: 12 mg (Ref).In combination with rolapitant: Oral, IV: 20 mg (Ref).Postchemotherapy days: Prophylaxis is not necessary on subsequent days (Ref).Moderately emetogenic chemotherapy (30% to 90% risk of emesis): Non-carboplatin-based regimens: Day of chemotherapy: Administer prior to chemotherapy and in combination with a 5-HT3 receptor antagonist: Oral, IV: 8 mg (Ref).Postchemotherapy days: Note: Consider single-agent dexamethasone use for regimens containing agents with known potential to induce delayed emesis (eg, oxaliplatin, cyclophosphamide, doxorubicin) (Ref); a single-day dexamethasone regimen may be employed when utilizing palonosetron (Ref); however, if a first-generation 5-HT3 antagonist was used on day 1 rather than palonosetron, some experts suggest the first-generation 5-HT3 receptor antagonist be continued for postchemotherapy emetic prophylaxis on days 2 and 3 (Ref).Oral, IV: 8 mg on days 2 and 3 (Ref).Low emetogenic risk (10% to 30% risk of emesis): Oral, IV: 4 to 8 mg administered as a single agent in a single dose prior to chemotherapy; prophylaxis is not necessary on subsequent days (Ref).Antiemetic regimens: Postoperative nausea and vomiting, preventionAntiemetic regimens: Postoperative nausea and vomiting, prevention (off-label use): Note: May be used alone or in combination with one or more other prophylactic interventions depending on risk factors (Ref).IV: 4 to 10 mg once, before or after induction of anesthesia. Dose depends on risk and type of surgery (Ref).Antiemetic regimens: Radiation therapy-associated nausea and vomiting, preventionAntiemetic regimens: Radiation therapy-associated nausea and vomiting, prevention (off-label use): High emetogenic risk radiation therapy (total body irradiation): Radiation day(s): Oral, IV: 4 mg once daily prior to each fraction of radiation; give in combination with a 5-HT3 receptor antagonist (Ref).Postradiation days: Oral, IV: The appropriate duration of therapy following radiotherapy days is not well defined; ASCO guidelines recommend continuing dexamethasone 4 mg once on the day after each day of radiation if radiation is not planned for that day (Ref).Moderate emetogenic risk radiation therapy (upper abdomen, craniospinal irradiation):Radiation day(s): Oral, IV: 4 mg once daily prior to each of the first 5 fractions of radiation; give in combination with a 5-HT3 receptor antagonist (Ref).Asthma, acute exacerbationAsthma, acute exacerbation (alternative agent) (off-label use): Note: Alternative to a longer course of other corticosteroids in mild to moderate exacerbations or in patients who do not respond promptly and completely to short-acting beta-agonists; administer within 1 hour of presentation to emergency department (Ref).Oral: 12 to 16 mg daily for 1 to 2 days only (Ref); longer treatment at this dose may be associated with metabolic adverse effects (Ref).Cancer-related cachexiaCancer-related cachexia (off-label use): Oral: 3 to 4 mg once daily; short-term therapy (weeks) is recommended, although duration of treatment depends on treatment goals and risk/benefit assessment (Ref) or 3 to 6 mg/day for up to 4 weeks (Ref).Cancer-related pain, advanced cancer, adjuvant therapyCancer-related pain, advanced cancer, adjuvant therapy (off-label use): Note: Although available data are limited and with mixed results, dexamethasone may provide clinical benefit in the management of a variety of types of pain in patients with advanced cancer (Ref). Due to the risk for potential toxicity, carefully consider the risks and benefits of glucocorticoid use for treating cancer-related pain, including the availability of other treatments, duration of treatment, other symptoms, and life expectancy.Low-dose regimen for pain and other symptoms in the context of advanced cancer and short prognosis: Oral, IV: Initial: 0.75 to 1.5 mg once or twice daily; usual effective dose range: 1 to 2 mg IV or orally twice daily (Ref).Higher-dose regimen for pain crisis that is poorly responsive to initial opioid therapy: Oral, IV: Initial: 8 to 10 mg once; if responsive, then may consider 4 mg twice daily or 8 mg once daily; use the lowest dose that maintains pain relief while other analgesic treatments are added, if indicated (Ref).Cerebral edema associated with brain tumorCerebral (vasogenic) edema associated with brain tumor: Moderate to severe symptoms (eg, lowered consciousness/brainstem dysfunction):Initial: IV: 10 mg once followed by maintenance dosing (Ref).Maintenance: IV, Oral: 4 mg every 6 hours (Ref). Note: Consider taper after 7 days of therapy; taper slowly over several weeks (Ref).Mild symptoms: IV, Oral: 4 to 8 mg/day in 1 to 4 divided doses (Ref). Note: Consider taper after 7 days of therapy; taper slowly over several weeks (Ref).COVID-19, hospitalized patientsCOVID-19, hospitalized patients (off-label use): Note: Dexamethasone is recommended for treatment of COVID-19 in hospitalized patients requiring supplemental oxygen or ventilatory support (Ref). An equivalent dose of an alternative glucocorticoid may be substituted if dexamethasone is unavailable (Ref).IV, Oral: 6 mg once daily for up to 10 days (or until discharge if sooner) as part of an appropriate combination regimen (Ref).Cushing syndrome, diagnosisCushing syndrome, diagnosis: Note: Interpretation requires evaluation of one or more of the following: serum cortisol concentration, serum dexamethasone concentration, urinary cortisol excretion, or 17-hydroxycorticosteroid excretion; consultation with a clinical endocrinologist is recommended (Ref).Initial testing:Overnight 1 mg dexamethasone suppression test: Oral: 1 mg given once between 11 PM and 12 AM (Ref).Longer low-dose dexamethasone suppression test (2 mg/day for 48 hours): Note: May be preferred in patients with depression, anxiety, obsessive-compulsive disorder, morbid obesity, alcoholism, or diabetes mellitus (Ref).Oral: 0.5 mg every 6 hours for 48 hours for a total of 8 doses; start time varies (eg, 9 AM or12 PM) (Ref).Fetal lung maturation, acceleration ofFetal lung maturation, acceleration of (maternal administration) (off-label use): Note: Generally, for patients between 24 and 34 weeks of gestation, including those with ruptured membranes or multiple gestations, who are at risk of delivering within 7 days. A single course may be appropriate in some pregnant patients beginning at 23 weeks' gestation or late preterm (between 34 0/7 weeks' and 36 6/7 weeks' gestation) who are at risk of delivering within 7 days.IM: 6 mg every 12 hours for a total of 4 doses. May repeat course in select patients (eg, patients with pregnancies up to 34 weeks' gestation at risk for delivery within 7 days and >14 days have elapsed since initial course of antenatal corticosteroids) (Ref).Immune thrombocytopeniaImmune thrombocytopenia (initial therapy): Note: Goal of therapy is to provide a safe platelet count to prevent clinically important bleeding rather than normalization of the platelet count (Ref).Oral, IV: 40 mg once daily for 4 days and then stop (no taper); may be repeated up to 3 times if inadequate response (Ref). For severe bleeding with thrombocytopenia, give in combination with other therapies (Ref).Iodinated contrast media allergic-like reaction, preventionIodinated contrast media allergic-like reaction, prevention (alternative agent): Note: Generally for patients with a prior allergic-like or unknown-type iodinated contrast reaction who will be receiving another iodinated contrast agent. Nonurgent premedication with an oral corticosteroid (eg, prednisone) is generally preferred when contrast administration is scheduled to begin in ≥12 hours; however, consider an urgent (accelerated) regimen with an IV corticosteroid for those requiring contrast in <12 hours. Efficacy of premedication regimens starting <4 to 5 hours before the use of contrast has not been demonstrated (Ref).Urgent (accelerated) regimen: IV: 7.5 mg every 4 hours until contrast medium administration in combination with diphenhydramine (Ref).Meningitis, prevention of neurologic complicationsMeningitis (bacterial), prevention of neurologic complications (off-label use): Note: Administer first dose of dexamethasone shortly before or at the same time as the first dose of antibacterials. If antibacterials have already been administered, do not administer dexamethasone. In patients with pneumococcal meningitis who receive dexamethasone, some experts recommend adding rifampin to the standard initial antibacterial regimen or adding rifampin if susceptibility tests, once available, show intermediate susceptibility (MIC ≥2 mcg/mL) to ceftriaxone and cefotaxime (Ref).Developed world (suspected or confirmed pneumococcal meningitis): IV: 0.15 mg/kg/dose or 10 mg every 6 hours for 4 days; discontinue if culture data reveal non-pneumococcal etiology (Ref).Developing world (strongly suspected or confirmed bacterial meningitis): IV: 0.4 mg/kg/dose every 12 hours for 4 days; discontinue if culture data reveal non-pneumococcal etiology; not recommended in regions with high rates of HIV infection and/or malnutrition or in cases of delayed clinical presentation (Ref).Migraine, recurrence preventionMigraine, recurrence prevention (off-label use): IM, IV: 10 to 24 mg once in combination with standard migraine abortive therapy (Ref).Multiple myelomaMultiple myeloma: Note: Multiple dexamethasone-containing regimens are available. Refer to literature/guidelines for additional details. For many regimens, dexamethasone is continued until disease progression or unacceptable toxicity. Dexamethasone total weekly dose may be split over 2 days when combination therapies are administered on successive days (refer to protocol) (Ref).Frail patients (eg, >75 years of age, BMI <18.5 kg/m2, poorly controlled diabetes, corticosteroid intolerance): When administered weekly, dexamethasone is usually reduced to 20 mg once weekly for frail patients (Ref). May consider lower initial dexamethasone doses (8 to 20 mg once weekly) in patients >75 years of age or those with comorbidities, with subsequent titration based on response/tolerance (Ref).Combination regimens that do not include a monoclonal antibody:Oral:40 mg once weekly on days 1, 8, 15, and 22 every 28 days in combination with lenalidomide (Ref), pomalidomide (Ref), ixazomib and lenalidomide (Ref), ixazomib and lenalidomide for 18 cycles (Ref), carfilzomib and lenalidomide (Ref), or bortezomib and lenalidomide (Ref) or 40 mg once weekly on days 1, 8, 15, and 22 every 28 days in cycles 1 to 9, and then 40 mg once weekly on days 1, 8, and 15 every 28 days beginning at cycle 10 (in combination with carfilzomib) (Ref).or20 mg on days 1, 8, 15, and 22 every 28 days (in combination with lenalidomide) for 9 cycles, followed by lenalidomide maintenance (Ref) or 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 every 21 days (in combination with bortezomib and lenalidomide) for 8 cycles (induction), followed by 40 mg on days 1, 8, 15, and 22 every 28 days (in combination with lenalidomide) for maintenance (Ref) or 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 every 28 days (in combination with carfilzomib) (Ref) or 20 mg on days 1 and 3 of each week (in combination with selinexor) (Ref) or 20 mg on days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 every 35 days (in combination with selinexor and bortezomib) (Ref).or40 mg once daily on days 1 to 4 and 9 to 12 every 28 days in combination with bortezomib and lenalidomide for 6 cycles followed by transplant (Ref) or 40 mg once daily on days 1 to 4, 9 to 12, and 17 to 20 every 28 days in combination with bortezomib and doxorubicin for 3 cycles as induction (Ref). Note: Some experts reserve this dosing (for 1 cycle, followed by 40 mg once weekly thereafter) for patients with an aggressive disease presentation or acute renal failure from light chain cast nephropathy (Ref).Combination regimens that include a monoclonal antibody:Oral, IV:40 mg weekly in combination with daratumumab and pomalidomide (Ref) or daratumumab/hyaluronidase and pomalidomide (Ref) or daratumumab and lenalidomide (Ref) or daratumumab/hyaluronidase and lenalidomide (Ref) or daratumumab and carfilzomib (Ref) or isatuximab and pomalidomide (Ref) or 20 mg once daily on days 1, 2, 4, 5, 8, 9, 11, and 12 every 21 days in combination with daratumumab and bortezomib (Ref) or 20 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 every 28 days in combination with isatuximab and carfilzomib (Ref). Note: In some studies, the dexamethasone dose is split over 2 days (20 mg before daratumumab and 20 mg the day after daratumumab infusion).or40 mg weekly, except on days elotuzumab is administered (administer dexamethasone 28 mg orally [8 mg orally in patients >75 years of age] plus 8 mg IV prior to elotuzumab) in combination with elotuzumab and pomalidomide (Ref) or elotuzumab and lenalidomide (Ref).Neoplastic epidural spinal cord compression, symptomaticNeoplastic epidural spinal cord compression, symptomatic: Note: As an adjunct to definitive treatment (radiotherapy or surgery), particularly in patients with neurologic deficits (Ref).IV (initial dose): 10 or 16 mg followed by oral dosing (Ref).Oral (after IV dose): 16 mg/day (usually given in 2 to 4 divided doses). Once definitive treatment is underway, taper gradually over 1 to 2 weeks until discontinuation (Ref).Tuberculosis, central nervous systemTuberculosis, central nervous system: Note: In general, steroids are indicated for patients with established or suspected tuberculous meningitis, regardless of HIV status (Ref).IV: Initial dose: 0.3 to 0.4 mg/kg/day for 2 weeks, then 0.2 mg/kg/day for week 3, then 0.1 mg/kg/day for week 4, followed by oral therapy (Ref).Oral: Starting week 5 of treatment: 4 mg/day, then taper by 1 mg of the daily dose each week; total combined IV/oral therapy duration: ~8 weeks (Ref).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultThe renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.Note: The pharmaco*kinetics and pharmacodynamics of corticosteroids in kidney impairment are not well understood (Ref). Dexamethasone half-life is decreased in patients with severe kidney impairment (Ref), potentially due to decreased protein binding (Ref); however, the clinical implications of these findings are unclear.Oral, parenteral:Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (Ref).Hemodialysis, intermittent (thrice weekly): No supplemental dose or dosage adjustment necessary (Ref).Peritoneal dialysis: No dosage adjustment necessary (Ref).CRRT: No dosage adjustment necessary (Ref).PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).Dosing: Hepatic Impairment: AdultThere are no dosage adjustments provided in the manufacturer’s labeling.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.[DSC] = Discontinued productConcentrate, Oral: Dexamethasone Intensol: 1 mg/mL (30 mL) [contains alcohol, usp; unflavored flavor]Elixir, Oral: Decadron: 0.5 mg/5 mL (237 mL [DSC]) [contains alcohol, usp, benzoic acid, fd&c red #40 (allura red ac dye), propylene glycol]Generic: 0.5 mg/5 mL (237 mL)Kit, Injection, as sodium phosphate: ReadySharp Dexamethasone: 10 mg/mL [DSC] [contains benzyl alcohol, sodium sulfite]TopiDex: 10 mg/mL [contains benzyl alcohol]Kit, Injection, as sodium phosphate [preservative free]: Active Injection D: 10 mg/mL [DSC]DoubleDex: 10 mg/mLMAS Care-Pak: 10 mg/mLSolution, Oral: Generic: 0.5 mg/5 mL (240 mL, 500 mL)Solution, Injection, as sodium phosphate: Generic: 4 mg/mL (1 mL); 20 mg/5 mL (5 mL); 120 mg/30 mL (30 mL); 10 mg/mL (1 mL); 100 mg/10 mL (10 mL)Solution, Injection, as sodium phosphate [preservative free]: Generic: 4 mg/mL (1 mL); 10 mg/mL (1 mL)Solution Prefilled Syringe, Injection, as sodium phosphate [preservative free]: Generic: 10 mg/mL (1 mL)Tablet, Oral: Decadron: 0.5 mg [DSC] [scored; contains fd&c yellow #5 (tartrazine), quinoline yellow (d&c yellow #10)]Decadron: 0.75 mg [DSC] [scored; contains fd&c blue #1 (brilliant blue), quinoline yellow (d&c yellow #10)]Decadron: 4 mg [DSC], 6 mg [DSC] [scored]Hemady: 20 mg [contains corn starch]Generic: 0.5 mg, 0.75 mg, 1 mg, 1.5 mg, 2 mg, 4 mg, 6 mgTablet Therapy Pack, Oral: Dexabliss: 1.5 MG (39) (39 ea)DexPak 10 Day: 1.5 mg (35 ea [DSC]) [scored; contains fd&c red #40(allura red ac)aluminum lake]DexPak 13 Day: 1.5 mg (51 ea [DSC]) [scored; contains fd&c red #40(allura red ac)aluminum lake]DexPak 6 Day: 1.5 mg (21 ea [DSC]) [scored; contains fd&c red #40(allura red ac)aluminum lake]Dxevo 11-Day: 1.5 mg (39 ea)Dxevo 11-Day: 1.5 mg (39 ea) [scored]HiDex 6-Day: 1.5 mg (21 ea) [scored; contains fd&c red #40 (allura red ac dye)]TaperDex 12-Day: 1.5 mg (49 ea) [contains fd&c red #40 (allura red ac dye)]TaperDex 6-Day: 1.5 mg (21 ea) [scored; contains fd&c red #40 (allura red ac dye)]TaperDex 6-Day: 1.5 mg (21 ea) [scored; contains fd&c red #40(allura red ac)aluminum lake]TaperDex 7-Day: 1.5 mg (27 ea) [scored; contains fd&c red #40 (allura red ac dye)]ZCORT 7-Day: 1.5 mg (25 ea [DSC]) [scored]Generic: 1.5 mg (21 ea, 35 ea, 51 ea)Generic Equivalent Available: USMay be product dependentDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Elixir, Oral: Generic: 0.5 mg/5 mL (100 ea, 100 mL)Solution, Injection, as sodium phosphate: Generic: 4 mg/mL (5 mL); 10 mg/mL (1 mL, 10 mL)Tablet, Oral: Generic: 0.5 mg, 0.75 mg, 2 mg, 4 mgAdministration: PediatricOral: May administer with food or milk to decrease GI adverse effects.Parenteral: Use preservative-free dosage forms in neonates.IM: May administer 4 mg/mL or 10 mg/mL undiluted.IV: May administer as undiluted solution (4 mg/mL or 10 mg/mL) slow IV push, usually over 1 to 4 minutes; rapid administration is associated with perineal discomfort (burning, tingling) (Ref); may consider further dilution of high doses and administration by IV intermittent infusion over 15 to 30 minutes (Ref).Administration: AdultOral: Administer with meals to help prevent GI upset. If appropriate, may administer antacids between meals to help prevent peptic ulcers.Oral concentrate: Use only the calibrated dropper provided. Draw dose into dropper; squeeze dropper contents into a liquid or semi-solid food (water, juice, soda or soda-like beverage, applesauce, pudding). Gently stir for a few seconds. Administer the entire mixture immediately. Do not store for future use.IV: May administer 4 mg/mL or 10 mg/mL concentration undiluted over ≥1 minute (Ref) or infuse by IVPB over 5 to 30 minutes (Ref). Rapid administration of dexamethasone may be associated with perineal irritation (especially with higher doses); consider further dilution and slower administration by IVPB to avoid perineal irritation (Ref).IM: Administer 4 mg/mL or 10 mg/mL concentration by deep IM injection.Intra-articular or soft tissue injection: Note: Dexamethasone sodium phosphate (a short-acting solution) is the only formulation available for intra-articular or soft tissue injections in the United States or Canada. Other glucocorticoids, such as triamcinolone acetonide or methylprednisolone acetate, are used more commonly for intra-articular or soft tissue injection (Ref). Refer to product-specific labeling for further details.Intra-articular: Administer into affected joint.Soft tissue: Administer into affected tissue.Intralesional injection: Note: Dexamethasone sodium phosphate (a short-acting solution) is the only formulation available for intralesional injections in the United States or Canada. Another glucocorticoid, triamcinolone acetonide, is used more commonly for intralesional injection (Ref). Refer to product-specific labeling for further details.Intralesional: Administer into affected area.Storage/StabilityElixir: Store at 15°C to 30°C (59°F to 86°F); avoid freezing.Injection: Store intact vials at 20°C to 25°C (68°F to 77°F). Protect from light, heat, and freezing. Do not autoclave. Diluted solutions should be used within 24 hours.Oral concentrated solution (Intensol): Store at 20°C to 25°C (68°F to 77°F); do not freeze; do not use if precipitate is present; dispense only in original bottle and only with manufacturer-supplied calibrated dropper; discard open bottle after 90 days.Oral solution, tablets: Store at 20°C to 25°C (68°F to 77°F); protect from moisture.Hemady (tablets): Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Dispense in a tight, light-resistant, child-resistant container.UseOral, parenteral: Primarily as an anti-inflammatory or immunosuppressant agent in the treatment of a variety of diseases, including those of allergic, hematologic, dermatologic, neoplastic, rheumatic, autoimmune, nervous system, renal, and respiratory origin (FDA approved in pediatric patients [age not specified] and adults); primary or secondary adrenocorticoid deficiency (not first line) (FDA approved in pediatric patients [age not specified] and adults); management of cerebral edema, shock, and as a diagnostic agent (FDA approved in pediatric patients [age not specified] and adults). Has also been used as adjunctive antiemetic agent in the treatment of chemotherapy-induced emesis, treatment of croup (laryngotracheobronchitis), treatment of airway edema prior to extubation, treatment of acute mountain sickness (AMS) and high altitude cerebral edema (HACE), and in neonates with bronchopulmonary dysplasia to facilitate ventilator weaning.Medication Safety IssuesSound-alike/look-alike issues:DexAMETHasone may be confused with desoximetasone, dexmedeTOMIDine, dextroamphetamineDecadron may be confused with PercodanAdverse Reactions (Significant): ConsiderationsAdrenal suppression (tertiary adrenal insufficiency)Adrenal suppression (tertiary adrenal insufficiency) may occur with glucocorticoids, including dexamethasone, and results from inadequate stimulation of the adrenal glands (Ref). Glucocorticoid-induced adrenal insufficiency usually resolves with discontinuation of dexamethasone, but symptoms may persist for 6 to 12 months (Ref). Adrenal insufficiency may lead to adrenal crisis, a life-threatening emergency that may present like a hypotensive shock state (Ref).Mechanism: Dose- and time-related; occurs due to lack of or diminished cortisol production by the adrenal gland (Ref). Exogenous glucocorticoids produce a similar negative feedback mechanism as endogenous cortisol, causing a subsequent decrease in adrenocorticotrophic hormone (ACTH) secretion; thus, cortisol production is suppressed resulting in adrenal atrophy and subsequent insufficiency (ie, hypothalamic-pituitary-adrenal-axis [HPA-axis] suppression) (Ref). In times of stress (eg, critical illness, trauma, surgery), the body requires stress doses in patients taking dexamethasone chronically (Ref). Primary adrenal insufficiency can be caused by dexamethasone alone (without fludrocortisone) because of its lack of mineralocorticoid activity (Ref).Onset: Varied; acute (minutes after administration) and/or chronic (2 to 20 hours to days) (Ref). Chronic dexamethasone use does not allow for the HPA axis to recover quickly (Ref).Risk factors: • High doses for prolonged periods: Although some patients may become HPA suppressed with lower doses or briefer exposure, some experts consider HPA axis-suppression likely in any adult receiving a dose comparable to prednisone >20 mg/day (daytime dosing) or a dose comparable to prednisone ≥5 mg per 24 hours (evening or night dosing) for >3 weeks or with cushingoid appearance (Ref)• Potency of glucocorticoids (Ref); dexamethasone is the most potent glucocorticoid for suppressing the HPA axis (Ref).• Abrupt withdrawal (Ref)• Concurrent interacting medications (eg, carbamazepine, St John's wort, mitotane, rifampicin, itraconazole, diltiazem, thyroid replacement therapy) (Ref)• History of previous adrenal crisis (Ref)• Use of glucocorticoid therapy delivered by various routes of administration (oral and inhaled greater risk than topical or intra-articular) (Ref)CNS and psychiatric/behavioral effectsGlucocorticoids, including dexamethasone, may cause a myriad of CNS and psychiatric/behavioral adverse reactions (Ref). Patients may develop apathy or depression. More commonly, patients develop excitatory psychiatric disturbances (including agitation, anxiety, distractibility, fear, hypomania, insomnia, irritability, lethargy, labile mood, mania, pressured speech, restlessness, and tearfulness) (Ref). Exact incidences are unclear but range from 1.8% to 57% (Ref). Severe psychiatric effects have been reported in 6% of adults receiving high-dose regimens, while depression or mania have been reported in 36% (Ref). Discontinuation or dose reductions generally resolve symptoms over days to weeks (Ref).Mechanism: Dose-related; not clearly established. Dexamethasone and other glucocorticoids may alter feedback on the hypothalamic-pituitary-adrenal axis, which may lead to mood changes (Ref). Glucocorticoids may induce glutamate release, which may be responsible for neuronal toxicity (Ref). Exogenous glucocorticoids may also impact GABAergic steroids (Ref).Onset: Varied; most cases occur early in treatment (within the first 5 days), average of 11.5 days. The majority develop within 6 weeks of initiation (Ref).Risk factors:• Higher doses (comparable to ≥80 mg prednisone) (Ref)Possible additional risk factors:• Age >30 years (Ref)• Females (Ref)• History of neuropsychiatric disorders (Ref)Cushingoid features/Cushing syndromeGlucocorticoids may cause a cushingoid appearance (truncal obesity, facial adipose tissue, dorsocervical adipose tissue), which are adverse reactions related to patient's physical features (Ref). Reactions are more metabolic than weight gain, which is related to fluid retention (edema) (Ref). Iatrogenic Cushing syndrome resulting from glucocorticoid therapy increases morbidity and mortality and decreases quality of life (Ref).Mechanism: Dose- and time-related; excess cortisol from exogenous source (dexamethasone) results in suppression of adrenocorticotrophic hormone (ACTH), commonly called iatrogenic Cushing syndrome (Ref).Onset: Delayed; may develop within the first 2 months of dexamethasone therapy, with the risk dependent on the dose and duration of treatment (Ref).Risk factors:• Higher doses (Ref)• Longer duration of use (Ref)• Drug interactions prolonging the half-life of glucocorticoids via cytochrome P450 (Ref)• BMI (high) (Ref)• Daily caloric intake (>30 kcal/kg/day) (Ref)GI effectsGlucocorticoids, including dexamethasone, may cause GI effects, including peptic ulcer (with possible perforation and hemorrhage), dyspepsia, gastritis, abdominal distention, and ulcerative esophagitis (Ref). Meta-analyses suggest that glucocorticoid monotherapy carries little to no risk of peptic ulcer disease in the general population (Ref). Studies have demonstrated an increased risk of focal small bowel perforation in infants with low birth weight receiving dexamethasone (Ref).Mechanism: Dose-related; glucocorticoids inhibit gastroprotective prostaglandin synthesis and reduce gastric mucus and bicarbonate secretion (Ref). Glucocorticoid immunosuppressive effects may prevent wound healing as well as mask GI signs and symptoms (Ref). Focal small bowel perforation is thought to be due to segmental degeneration of the muscularis externa (Ref).Risk factors:• Higher doses (equivalent to methylprednisolone ≥4 mg/day) (Ref)• Concurrent aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) (Ref)• Hospitalized (but not ambulatory) patients (Ref)• Infants with low birth weight (Ref)• Recent glucocorticoid users (7 to 28 days) versus remote or nonusers (Ref)HyperglycemiaGlucocorticoids, including dexamethasone, may provoke new-onset hyperglycemia in patients without a history of diabetes and may cause an exacerbation of diabetes mellitus (Ref). Glucose levels have been noted to increase 68% above baseline (Ref). Certain patient populations (eg, transplant, cancer, chronic rheumatologic conditions) are at particular risk due to medication combinations (Ref). Resolution may occur within 24 to 36 hours after dexamethasone discontinuation (Ref).Mechanism: Dose- and time-related; increased insulin resistance (Ref). May also interfere with insulin signaling by direct effects on the insulin receptor and the glucose transporter and may promote gluconeogenesis via liver stimulation (Ref).Onset: Rapid; 4 hours (Ref). Rapid onset of steroid-induced hyperglycemia occurred within 2 days after initiation of glucocorticoids with a peak in the late afternoon following daily dosing in the morning (Ref).Risk factors:• Dose and type of glucocorticoid (Ref)• Duration of use (Ref)• Divided versus once-daily dosing (Ref)• IV and oral routes of administration (Ref)• Older age (Ref)• Males (Ref)• BMI >25 kg/m2 (Ref)• African American or Hispanic (Ref)• eGFR <40 mL/minute/1.73 m2 (Ref)• HbA1c ≥6% (Ref)• History of gestational diabetes (Ref)• Family history of diabetes mellitus (Ref)• Concurrent use of mycophenolate mofetil and calcineurin inhibitors (Ref)• Previous history of impaired fasting glucose or impaired glucose tolerance (Ref)• Patients receiving palliative care (Ref)InfectionGlucocorticoids, including dexamethasone, have immunosuppressive and anti-inflammatory effects that are reversible with discontinuation. Infection may occur after prolonged use, including Pneumocystis jirovecii pneumonia (PJP), herpes zoster, tuberculosis, and other more common bacterial infections (Ref).Mechanism: Dose- and time-related; related to pharmacologic action (ie, multiple activities on cell macrophage production and differentiation, inhibition of T-cell activation, and effects on dendritic cells) (Ref).Onset: Varied; in one study, the median duration of glucocorticoid use prior to PJP diagnosis was 12 weeks but also occurred earlier or later in some cases (Ref).Risk factors:• Higher dose and longer duration of glucocorticoid (Ref); however, may also increase risk at lower doses (eg, ≤5 mg/day of prednisone or equivalent) (Ref).• Immunocompromised state (Ref)• Concurrent medications (immunosuppressive) (Ref)• Rheumatoid arthritis (Ref)• Interstitial lung disease (Ref)• Older adults (Ref)• Male (Ref)• Low performance status (Ref)Neuromuscular and skeletal effectsGlucocorticoid (including dexamethasone)-induced neuromuscular and skeletal effects can take the form of various pathologies in patients ranging from osteoporosis and vertebral compression fracture to myopathy to osteonecrosis in adult and pediatric patients (Ref). Glucocorticoid use is the most common cause of secondary osteoporosis; may be underrecognized and undertreated due to underestimation of risk in this patient population (Ref). Vertebral fractures are the most common glucocorticoid-related fracture (Ref). Myopathies can also occur secondary to direct skeletal muscle catabolism (Ref). Acute steroid myopathy is rare (Ref).Mechanism: Dose- and time-related; glucocorticoids have direct/indirect effects on bone remodeling with osteoblast recruitment decreasing and apoptosis increasing (Ref). Myopathies or myasthenia result from reductions in protein synthesis and protein catabolism, which can manifest as proximal muscle weakness and atrophy in the upper and lower extremities (Ref).Onset: Delayed; vertebral fracture risk is increased within 3 months of initiation and peaks at 12 months (Ref).Risk factors:Drug-related risks:• Cumulative dose of glucocorticoids prednisone >5 g or equivalent (Ref)• Children receiving ≥4 courses of glucocorticoids (Ref)• Prednisone ≥2.5 mg to 7.5 mg daily or equivalent for ≥3 months (Ref)• Myopathy may occur at prednisone doses ≥10 mg daily or equivalent, with higher doses potentiating more of a rapid onset (Ref)• Fluorinated glucocorticoid preparations (eg, dexamethasone, betamethasone, triamcinolone) have a higher risk of myopathies (Ref)General fracture risks:• Age >55 years (Ref)• BMI <18.5 kg/m2 (Ref)• Bone mineral T score below -1.5 (Ref)• Endocrine disorders (eg, hypogonadism, hyper- or hypoparathyroidism) (Ref)• Excess alcohol use (>2 units/day) (Ref)• Females (Ref)• History of falls (Ref)• Malabsorption (Ref)• Menopause and duration of menopause (Ref)• White race (Ref)• Patients with cancer (Ref)• Previous fracture (Ref)• Smoking (Ref)• Underlying inflammatory condition in all ages (eg, inflammatory bowel disease, rheumatoid arthritis) (Ref)Ocular effectsGlucocorticoid (including dexamethasone)-induced ocular effects may include increased intraocular pressure (IOP), glaucoma (open-angle), and subcapsular posterior cataract in adult and pediatric patients (Ref). Cataracts may persist after discontinuation of glucocorticoid therapy (Ref).Mechanism: Dose- and time-related; Glucocorticoids can induce cataracts by covalently bonding to lens proteins, causing destabilization of the protein structure, and oxidative changes leading to cataracts formation (Ref). There are various proposed mechanisms of IOP contributing to glaucoma, including accumulation of polymerized glycosaminoglycans in the trabecular meshwork, producing edema and increasing outflow resistance (Ref). Another mechanism may include inhibition of phagocytic endothelial cells, leading to accumulation of aqueous debris (Ref). Glucocorticoids can also alter the trabecular meshwork causing an increase in nuclear size and DNA content (Ref). In addition, they can decrease the synthesis of prostaglandins which regulate the aqueous outflow (Ref).Onset: Delayed; cataracts may occur at least 1 year after initiation of chronic glucocorticoid therapy (Ref). IOP may occur at 4 years or more after initiation (Ref).Risk factors:• Dose (Ref)• Topical > Systemic (Ref)• Duration of use in all ages (Ref)• Family history of open-angle glaucoma (Ref)• Type I diabetes mellitus (Ref)• High myopia (Ref)• Pseudophakia (Ref)• Prior vitrectomies (Ref)• Connective tissue disease and sex (eg, rheumatoid arthritis in males) (Ref)• Older patients or age <6 years (Ref)• Genetics (Ref)• Angle recessive glaucoma (Ref)Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Some reactions listed are based on reports for other agents in this same pharmacologic class and may not be specifically reported for dexamethasone.Frequency not defined:Cardiovascular: Bradycardia, cardiac arrhythmia, cardiomegaly, circulatory shock, edema, embolism (fat), heart failure (in susceptible patients), hypertension, myocardial rupture (after recent myocardial infarction), syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitisDermatologic: Acne vulgaris, allergic dermatitis, alopecia, atrophic striae, diaphoresis, ecchymoses, erythema of skin, facial erythema, fragile skin, hyperpigmentation, hypertrichosis, hypopigmentation, inadvertent suppression of skin test reaction, perianal skin irritation (itching, burning, tingling; following rapid IV injection; more common in females, with higher doses; sudden onset with resolution in <1 minute) (Allan 1986; Neff 2002; Perron 2003; Singh 2011), skin atrophy, skin rash, subcutaneous atrophy, urticaria, xerodermaEndocrine & metabolic: Decreased serum potassium, fluid retention, growth suppression (children), hirsutism, hypokalemic alkalosis, menstrual disease, negative nitrogen balance (due to protein catabolism), sodium retention, weight gainGastrointestinal: Hiccups, increased appetite, nausea, pancreatitis, pruritus ani (following IV injection)Genitourinary: Defective spermatogenesis (increased or decreased), glycosuriaHematologic & oncologic: Kaposi sarcoma (Goedert 2002), petechiaHepatic: Hepatomegaly, increased serum transaminasesHypersensitivity: Anaphylaxis, angioedema, nonimmune anaphylaxisInfection: Sterile abscessLocal: Postinjection flare (intra-articular use)Nervous system: Amyotrophy, emotional lability, euphoria, headache, increased intracranial pressure, intracranial hypertension (idiopathic; usually following discontinuation), malaise, myasthenia, neuritis, neuropathy, paresthesia, personality changes, seizure, vertigoNeuromuscular & skeletal: Charcot arthropathy, rupture of tendonOphthalmic: ExophthalmosRespiratory: Pulmonary edemaMiscellaneous: Wound healing impairmentPostmarketing:Cardiovascular: Hypertrophic cardiomyopathy (premature infants) (Kale 2015)Endocrine & metabolic: Adrenal suppression (tertiary) (Dineen 2019), Cushing syndrome (iatrogenic) (Hopkins 2005), cushingoid appearance (Hopkins 2005), exacerbation of diabetes mellitus (Tamez-Pérez 2015), hyperglycemia (Tamez-Pérez 2015), impaired glucose tolerance (Tamez-Pérez 2015), moon face (Hopkins 2005), redistribution of body fat (Hopkins 2005)Gastrointestinal: Abdominal distention (Liu 2013), intestinal perforation (Gordon 1999, Gordon 2001), peptic ulcer (with possible perforation and hemorrhage) (Liu 2013), ulcerative esophagitis (Liu 2013)Hematologic & oncologic: Tumor lysis syndrome (Chanimov 2006)Infection: Infection (Youssef 2016)Nervous system: Apathy (Ciriaco 2013, Warrington 2006), depression (Ciriaco 2013, Warrington 2006), psychiatric disturbance (including agitation, anxiety, distractibility, euphoria, fear, hypomania, insomnia, irritability, labile mood, lethargy, pressured speech, restlessness, tearfulness) (Ciriaco 2013, Warrington 2006)Neuromuscular & skeletal: Bone fracture (Buckley 2018), myopathy (Liu 2013), osteonecrosis (femoral and humoral heads) (Liu 2013), osteoporosis (Buckley 2018), steroid myopathy (Haran 2018), vertebral compression fracture (Buckley 2018)Ophthalmic: Glaucoma (Phulke 2017), increased intraocular pressure (Phulke 2017), subcapsular posterior cataract (Urban 1986)ContraindicationsHypersensitivity to dexamethasone or any component of the formulation; systemic fungal infectionsDocumentation of allergenic cross-reactivity for corticosteroids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.Warnings/PrecautionsConcerns related to adverse effects:• Adrenal suppression: May cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal axis, particularly in younger children.Disease-related concerns:• Adrenal insufficiency: Dexamethasone does not provide any mineralocorticoid activity in adrenal insufficiency (may be employed as a single dose while cortisol assays are performed). Hydrocortisone is the preferred treatment of chronic primary adrenal insufficiency and adrenal crisis (ES [Bornstein 2016]).• Cardiovascular disease: Use with caution in patients with heart failure and/or hypertension; use has been associated with fluid retention, electrolyte disturbances, and hypertension. Monitor BP. Use with caution following acute myocardial infarction; corticosteroids have been associated with myocardial rupture.• GI disease: Use with caution in patients with GI diseases (diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer, ulcerative colitis, abscess, or other pyogenic infection) due to GI perforation risk. Signs of GI perforation may be masked in patients receiving corticosteroid therapy.• Head injury: Increased mortality was observed in patients receiving high-dose IV methylprednisolone. High-dose corticosteroids should not be used for the management of head injury (BTF [Carney 2016]).• Hepatic impairment: Use with caution in patients with hepatic impairment, including cirrhosis; long-term use has been associated with fluid retention.• Hepatitis B: Reactivation may occur.• Myasthenia gravis: Use may cause transient worsening of myasthenia gravis (MG) (eg, within first 2 weeks of treatment); monitor for worsening MG (AAN [Narayanaswami 2021]).• Ocular disease: Use with caution in patients with a history of ocular herpes simplex; corneal perforation has occurred; do not use in active ocular herpes simplex. Not recommended for the treatment of optic neuritis; may increase frequency of new episodes.• Pheochromocytoma: Pheochromocytoma crisis (may be fatal) has been reported after administration of systemic corticosteroids. Consider the risk of pheochromocytoma crisis in patients with suspected or confirmed pheochromocytoma.• Renal impairment: Use with caution in patients with renal impairment; fluid retention may occur.• Seizure disorders: Use corticosteroids with caution in patients with a history of seizure disorder; seizures have been reported with adrenal crisis.• Systemic sclerosis: Use with caution in patients with systemic sclerosis; an increase in scleroderma renal crisis incidence has been observed with corticosteroid use. Monitor BP and renal function in patients with systemic sclerosis treated with corticosteroids (EULAR [Kowal-Bielecka 2017]).• Thyroid disease: Changes in thyroid status may necessitate dosage adjustments; metabolic clearance of corticosteroids increases in hyperthyroid patients and decreases in hypothyroid patients.Concurrent drug therapy issues:• Immunizations: Avoid administration of live or live attenuated vaccines in patients receiving immunosuppressive doses of corticosteroids. Non-live or inactivated vaccines may be administered, although the response cannot be predicted.Special populations:• Older adult: Use with caution in elderly patients with the smallest possible effective dose for the shortest duration.• Pediatric: May affect growth velocity; growth should be routinely monitored in pediatric patients.Dosage form specific issues:• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP ["Inactive" 1997]; Zar 2007).• Sulfite: Some products may contain sodium sulfite, a sulfite that may cause allergic-type reactions including anaphylaxis and life-threatening or less severe asthmatic episodes in susceptible patients.Other warnings/precautions:• Discontinuation of therapy: Withdraw therapy with gradual tapering of dose.• Epidural injection: Corticosteroids are not approved for epidural injection. Serious neurologic events (eg, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, stroke), some resulting in death, have been reported with epidural injection of corticosteroids, with and without use of fluoroscopy.• Intra-articular injection: May produce systemic as well as local effects. Appropriate examination of any joint fluid present is necessary to exclude a septic process. Avoid injection into an infected site. Do not inject into unstable joints. Patients should not overuse joints in which symptomatic benefit has been obtained as long as the inflammatory process remains active. Frequent intra-articular injection may result in damage to joint tissues.Warnings: Additional Pediatric ConsiderationsIn premature neonates, the use of high-dose dexamethasone (approximately >0.5 mg/kg/day) for the prevention or treatment of bronchopulmonary dysplasia has been associated with adverse neurodevelopmental outcomes, including higher rates of cerebral palsy without additional clinical benefit over lower doses; current data do not support use of high doses; further studies are needed (Watterberg 2010).Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities, which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults, including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).Metabolism/Transport EffectsSubstrate of CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP3A4 (weak)Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions programAbrocitinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Abrocitinib.Management: The use of abrocitinib in combination with other immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive. Risk D: Consider therapy modificationAcetylcholinesterase Inhibitors: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur.Risk C: Monitor therapyAldesleukin: Corticosteroids may diminish the antineoplastic effect of Aldesleukin.Risk X: Avoid combinationAmphotericin B: Corticosteroids (Systemic) may enhance the hypokalemic effect of Amphotericin B.Risk C: Monitor therapyAndrogens: Corticosteroids (Systemic) may enhance the fluid-retaining effect of Androgens.Risk C: Monitor therapyAntacids: May decrease the bioavailability of Corticosteroids (Oral). Management: Consider separating doses by 2 or more hours. Budesonide enteric coated tablets could dissolve prematurely if given with drugs that lower gastric acid, with unknown impact on budesonide therapeutic effects. Risk D: Consider therapy modificationAntidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.Risk C: Monitor therapyAprepitant: May increase the serum concentration of DexAMETHasone (Systemic). Management: Reduce dexamethasone dose 50% with aprepitant. Aprepitant labeling incorporates this recommendation into the dose provided for dexamethasone; further reduction is not necessary. No dose adjustment may be needed with single, low-dose aprepitant for PONV. Risk D: Consider therapy modificationBaricitinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Baricitinib.Management: The use of baricitinib in combination with potent immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive. Risk D: Consider therapy modificationBCG Products: Corticosteroids (Systemic) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of BCG Products.Risk X: Avoid combinationBile Acid Sequestrants: May decrease the absorption of Corticosteroids (Oral). Risk C: Monitor therapyBrincidofovir: Corticosteroids (Systemic) may diminish the therapeutic effect of Brincidofovir.Risk C: Monitor therapyCalcitriol (Systemic): Corticosteroids (Systemic) may diminish the therapeutic effect of Calcitriol (Systemic).Risk C: Monitor therapyCAR-T Cell Immunotherapy: Corticosteroids (Systemic) may enhance the adverse/toxic effect of CAR-T Cell Immunotherapy. Specifically, the severity and duration of neurologic toxicities may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of CAR-T Cell Immunotherapy.Management: Avoid use of corticosteroids as premedication before treatment with CAR-T cell immunotherapy agents. Corticosteroids are indicated and may be required for treatment of toxicities such as cytokine release syndrome or neurologic toxicity. Risk D: Consider therapy modificationCaspofungin: Inducers of Drug Clearance may decrease the serum concentration of Caspofungin.Management: Consider using an increased caspofungin dose of 70 mg daily in adults (or 70 mg/m2, up to a maximum of 70 mg, daily in pediatric patients) when coadministered with known inducers of drug clearance. Risk D: Consider therapy modificationCladribine: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Cladribine.Risk X: Avoid combinationClofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapyCloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine.Risk C: Monitor therapyCobicistat: May increase the serum concentration of DexAMETHasone (Systemic). Dexamethasone (Systemic) may also counteract the boosting effects of Cobicistat on some agents. DexAMETHasone (Systemic) may increase the serum concentration of Cobicistat. Management: Consider an alternative corticosteroid. Monitor patients receiving this combination closely for evidence of diminished response to the antiviral regimen. Risk D: Consider therapy modificationCoccidioides immitis Skin Test: Corticosteroids (Systemic) may diminish the diagnostic effect of Coccidioides immitis Skin Test.Management: Consider discontinuing systemic corticosteroids (dosed at 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks) several weeks prior to coccidioides immitis skin antigen testing. Risk D: Consider therapy modificationCorticorelin: Corticosteroids (Systemic) may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy.Risk C: Monitor therapyCosyntropin: Corticosteroids (Systemic) may diminish the diagnostic effect of Cosyntropin.Risk C: Monitor therapyCOVID-19 Vaccine (Adenovirus Vector): Corticosteroids (Systemic) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector).Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters) Risk D: Consider therapy modificationCOVID-19 Vaccine (Inactivated Virus): Corticosteroids (Systemic) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus).Risk C: Monitor therapyCOVID-19 Vaccine (mRNA): Corticosteroids (Systemic) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA).Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modificationCOVID-19 Vaccine (Subunit): Corticosteroids (Systemic) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit).Risk C: Monitor therapyCOVID-19 Vaccine (Virus-like Particles): Corticosteroids (Systemic) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles).Risk C: Monitor therapyCYP3A4 Inducers (Moderate): May decrease the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapyCYP3A4 Inducers (Strong): May decrease the serum concentration of DexAMETHasone (Systemic). Management: Consider dexamethasone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced dexamethasone efficacy. Consider avoiding this combination when treating life threatening conditions (ie, multiple myeloma). Risk D: Consider therapy modificationCYP3A4 Inhibitors (Moderate): May increase the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapyCYP3A4 Inhibitors (Strong): May increase the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapyDeferasirox: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased.Risk C: Monitor therapyDelavirdine: DexAMETHasone (Systemic) may decrease the serum concentration of Delavirdine.Risk C: Monitor therapyDengue Tetravalent Vaccine (Live): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live).Risk X: Avoid combinationDenosumab: May enhance the immunosuppressive effect of Corticosteroids (Systemic). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and systemic corticosteroids. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modificationDesirudin: Corticosteroids (Systemic) may enhance the anticoagulant effect of Desirudin. More specifically, corticosteroids may increase hemorrhagic risk during desirudin treatment.Management: Discontinue treatment with systemic corticosteroids prior to desirudin initiation.If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Risk D: Consider therapy modificationDesmopressin: Corticosteroids (Systemic) may enhance the hyponatremic effect of Desmopressin.Risk X: Avoid combinationDeucravacitinib: May enhance the immunosuppressive effect of Corticosteroids (Systemic). Management: The use of deucravacitinib in combination with potent immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive. Risk D: Consider therapy modificationDisulfiram: May enhance the adverse/toxic effect of Products Containing Ethanol. Management: Do not use disulfiram with dosage forms that contain ethanol. Risk X: Avoid combinationElvitegravir: DexAMETHasone (Systemic) may decrease the serum concentration of Elvitegravir.Management: Consider using an alternative corticosteroid.Monitor patients receiving these agents in combination for diminished antiviral response. Risk D: Consider therapy modificationEPHEDrine (Systemic): May decrease the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapyEstrogen Derivatives: May increase the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapyFexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combinationFilgotinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Filgotinib.Management: Coadministration of filgotinib with systemic corticosteroids at doses equivalent to greater than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks is not recommended. Risk D: Consider therapy modificationFosamprenavir: DexAMETHasone (Systemic) may decrease the serum concentration of Fosamprenavir. Fosamprenavir may increase the serum concentration of DexAMETHasone (Systemic).Risk C: Monitor therapyFosaprepitant: May increase the serum concentration of DexAMETHasone (Systemic). Management: Reduce the dexamethasone dose 50% when coadministered with aprepitant. Aprepitant prescribing information incorporates this recommendation into the dose provided for dexamethasone; further reduction is not necessary. Risk D: Consider therapy modificationFosnetupitant: May increase the serum concentration of DexAMETHasone (Systemic). Management: Decrease dexamethasone doses to 12 mg on day 1, and if needed based on the emetic potential of the regimen, 8 mg daily on days 2 to 4 of chemotherapy when administered with fosnetupitant. Risk D: Consider therapy modificationFosphenytoin: May decrease the serum concentration of DexAMETHasone (Systemic). DexAMETHasone (Systemic) may decrease the serum concentration of Fosphenytoin. DexAMETHasone (Systemic) may increase the serum concentration of Fosphenytoin. Management: Consider dexamethasone dose increases when combined with fosphenytoin and monitor closely for reduced steroid efficacy. Monitor phenytoin levels closely, both increased and decreased phenytoin levels have been reported. Risk D: Consider therapy modificationFusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combinationGallium Ga 68 Dotatate: Corticosteroids (Systemic) may diminish the diagnostic effect of Gallium Ga 68 Dotatate.Risk C: Monitor therapyGrowth Hormone Analogs: Corticosteroids (Systemic) may diminish the therapeutic effect of Growth Hormone Analogs. Growth Hormone Analogs may decrease serum concentrations of the active metabolite(s) of Corticosteroids (Systemic).Risk C: Monitor therapyHormonal Contraceptives: CYP3A4 Inducers (Weak) may decrease the serum concentration of Hormonal Contraceptives.Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a weak CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modificationHyaluronidase: Corticosteroids (Systemic) may diminish the therapeutic effect of Hyaluronidase.Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Risk D: Consider therapy modificationImatinib: DexAMETHasone (Systemic) may decrease the serum concentration of Imatinib.Management: Avoid concurrent use of imatinib with dexamethasone when possible.If such a combination must be used, increase imatinib dose by at least 50% and monitor clinical response closely. Risk D: Consider therapy modificationImmune Checkpoint Inhibitors: Corticosteroids (Systemic) may diminish the therapeutic effect of Immune Checkpoint Inhibitors.Management: Carefully consider the need for corticosteroids, at doses of a prednisone-equivalent of 10 mg or more per day, during the initiation of immune checkpoint inhibitor therapy. Use of corticosteroids to treat immune related adverse events is still recommended Risk D: Consider therapy modificationIndium 111 Capromab Pendetide: Corticosteroids (Systemic) may diminish the diagnostic effect of Indium 111 Capromab Pendetide.Risk X: Avoid combinationInebilizumab: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Inebilizumab.Risk C: Monitor therapyInfluenza Virus Vaccines: Corticosteroids (Systemic) may diminish the therapeutic effect of Influenza Virus Vaccines.Management: Administer influenza vaccines at least 2 weeks prior to initiation of systemic corticosteroids at immunosuppressive doses. Influenza vaccines administered less than 14 days prior to or during such therapy should be repeated 3 months after therapy. Risk D: Consider therapy modificationIsoniazid: Corticosteroids (Systemic) may decrease the serum concentration of Isoniazid.Risk C: Monitor therapyLapatinib: DexAMETHasone (Systemic) may decrease the serum concentration of Lapatinib.Management: If therapy overlap cannot be avoided, consider titrating lapatinib gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic breast cancer) or 1,500 mg/day up to 5,500 mg/day (hormone receptor/HER2 positive breast cancer) as tolerated. Risk X: Avoid combinationLeflunomide: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Leflunomide.Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as systemic corticosteroids. Risk D: Consider therapy modificationLenalidomide: DexAMETHasone (Systemic) may enhance the thrombogenic effect of Lenalidomide.Management: Consider using venous thromboembolism prophylaxis (eg, low-molecular weight heparin or warfarin [INR 2.0-3.0]) in patients with multiple myeloma who are receiving lenalidomide and dexamethasone. Risk D: Consider therapy modificationLicorice: May increase the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapyLoop Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Loop Diuretics.Risk C: Monitor therapyLopinavir: DexAMETHasone (Systemic) may decrease the serum concentration of Lopinavir.Management: Consider alternative corticosteroids for coadministration with lopinavir/ritonavir due to the potential for dexamethasone to decrease lopinavir/ritonavir efficacy and result in the development of resistance. Risk D: Consider therapy modificationLutetium Lu 177 Dotatate: Corticosteroids (Systemic) may diminish the therapeutic effect of Lutetium Lu 177 Dotatate.Management: Avoid repeated use of high-doses of corticosteroids during treatment with lutetium Lu 177 dotatate. Use of corticosteroids is still permitted for the treatment of neuroendocrine hormonal crisis. The effects of lower corticosteroid doses is unknown. Risk D: Consider therapy modificationMacimorelin: Corticosteroids (Systemic) may diminish the diagnostic effect of Macimorelin.Risk X: Avoid combinationMethotrimeprazine: Products Containing Ethanol may enhance the adverse/toxic effect of Methotrimeprazine. Specifically, CNS depressant effects may be increased.Management: Avoid products containing alcohol in patients treated with methotrimeprazine. Risk X: Avoid combinationMetyraPONE: Corticosteroids (Systemic) may diminish the diagnostic effect of MetyraPONE.Management: Consider alternatives to the use of the metyrapone test in patients taking systemic corticosteroids. Risk D: Consider therapy modificationMifamurtide: Corticosteroids (Systemic) may diminish the therapeutic effect of Mifamurtide.Risk X: Avoid combinationMiFEPRIStone: May diminish the therapeutic effect of Corticosteroids (Systemic). MiFEPRIStone may increase the serum concentration of Corticosteroids (Systemic). Management: Avoid mifepristone in patients who require long-term corticosteroid treatment of serious illnesses or conditions (eg, for immunosuppression following transplantation). Corticosteroid effects may be reduced by mifepristone treatment. Risk X: Avoid combinationNatalizumab: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Natalizumab.Risk X: Avoid combinationNetupitant: May increase the serum concentration of DexAMETHasone (Systemic). Management: Decrease dexamethasone doses to 12 mg on day 1, and if needed based on the emetic potential of the regimen, 8 mg daily on days 2 to 4 of chemotherapy when administered with netupitant. Risk D: Consider therapy modificationNeuromuscular-Blocking Agents (Nondepolarizing): May enhance the adverse neuromuscular effect of Corticosteroids (Systemic). Increased muscle weakness, possibly progressing to polyneuropathies and myopathies, may occur. Management: If concomitant therapy is required, use the lowest dose for the shortest duration to limit the risk of myopathy or neuropathy. Monitor for new onset or worsening muscle weakness, reduction or loss of deep tendon reflexes, and peripheral sensory decriments Risk D: Consider therapy modificationNicorandil: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nicorandil. Gastrointestinal perforation has been reported in association with this combination.Risk C: Monitor therapyNiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine.Risk C: Monitor therapyNirmatrelvir and Ritonavir: May increase the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapyNonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective).Risk C: Monitor therapyNonsteroidal Anti-Inflammatory Agents (Nonselective): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective).Risk C: Monitor therapyNonsteroidal Anti-Inflammatory Agents (Topical): May enhance the adverse/toxic effect of Corticosteroids (Systemic). Specifically, the risk of gastrointestinal bleeding, ulceration, and perforation may be increased. Risk C: Monitor therapyOcrelizumab: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Ocrelizumab.Risk C: Monitor therapyOfatumumab: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Ofatumumab.Risk C: Monitor therapyOrnidazole: May enhance the adverse/toxic effect of Products Containing Ethanol. Specifically, a disulfiram-like reaction may occur. Risk X: Avoid combinationPhenytoin: May decrease the serum concentration of DexAMETHasone (Systemic). DexAMETHasone (Systemic) may decrease the serum concentration of Phenytoin. DexAMETHasone (Systemic) may increase the serum concentration of Phenytoin. Management: Consider dexamethasone dose increases when combined with phenytoin and monitor closely for reduced steroid efficacy. Monitor phenytoin levels closely when combined with dexamethasone, both increased and decreased phenytoin levels have been reported. Risk D: Consider therapy modificationPidotimod: Corticosteroids (Systemic) may diminish the therapeutic effect of Pidotimod.Risk C: Monitor therapyPimecrolimus: May enhance the immunosuppressive effect of Corticosteroids (Systemic). Risk X: Avoid combinationPneumococcal Vaccines: Corticosteroids (Systemic) may diminish the therapeutic effect of Pneumococcal Vaccines.Risk C: Monitor therapyPoliovirus Vaccine (Live/Trivalent/Oral): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral).Risk X: Avoid combinationPolymethylmethacrylate: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Polymethylmethacrylate. Specifically, the risk for hypersensitivity or implant clearance may be increased.Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modificationQuinolones: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Quinolones. Specifically, the risk of tendonitis and tendon rupture may be increased.Risk C: Monitor therapyRabies Vaccine: Corticosteroids (Systemic) may diminish the therapeutic effect of Rabies Vaccine.Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modificationRilpivirine: DexAMETHasone (Systemic) may decrease the serum concentration of Rilpivirine.Risk X: Avoid combinationRitodrine: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Ritodrine.Risk C: Monitor therapyRubella- or Varicella-Containing Live Vaccines: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines.Risk X: Avoid combinationRuxolitinib (Topical): Corticosteroids (Systemic) may enhance the immunosuppressive effect of Ruxolitinib (Topical).Risk X: Avoid combinationSalicylates: May enhance the adverse/toxic effect of Corticosteroids (Systemic). These specifically include gastrointestinal ulceration and bleeding. Corticosteroids (Systemic) may decrease the serum concentration of Salicylates. Withdrawal of corticosteroids may result in salicylate toxicity. Risk C: Monitor therapySaquinavir: DexAMETHasone (Systemic) may decrease the serum concentration of Saquinavir.Management: Consider alternatives to this combination if possible, due to the potential for decreased saquinavir/ritonavir therapeutic effect and the potential development of resistance. Risk D: Consider therapy modificationSargramostim: Corticosteroids (Systemic) may enhance the therapeutic effect of Sargramostim. Specifically, corticosteroids may enhance the myeloproliferative effects of sargramostim.Risk C: Monitor therapySecnidazole: Products Containing Ethanol may enhance the adverse/toxic effect of Secnidazole.Risk X: Avoid combinationSelpercatinib: CYP3A4 Inducers (Weak) may decrease the serum concentration of Selpercatinib.Risk C: Monitor therapySimeprevir: DexAMETHasone (Systemic) may decrease the serum concentration of Simeprevir.Risk X: Avoid combinationSipuleucel-T: Corticosteroids (Systemic) may diminish the therapeutic effect of Sipuleucel-T.Management: Consider reducing the dose or discontinuing immunosuppressants, such as systemic corticosteroids, prior to initiating sipuleucel-T therapy. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone given for 2 or more weeks are immunosuppressive. Risk D: Consider therapy modificationSirolimus (Conventional): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Conventional).Risk C: Monitor therapySirolimus (Protein Bound): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Protein Bound).Risk C: Monitor therapySodium Benzoate: Corticosteroids (Systemic) may diminish the therapeutic effect of Sodium Benzoate.Risk C: Monitor therapySphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Corticosteroids (Systemic). Risk C: Monitor therapySuccinylcholine: Corticosteroids (Systemic) may enhance the neuromuscular-blocking effect of Succinylcholine.Risk C: Monitor therapyTacrolimus (Systemic): Corticosteroids (Systemic) may decrease the serum concentration of Tacrolimus (Systemic). Conversely, when discontinuing corticosteroid therapy, tacrolimus concentrations may increase.Risk C: Monitor therapyTacrolimus (Systemic): CYP3A4 Inducers (Weak) may decrease the serum concentration of Tacrolimus (Systemic).Risk C: Monitor therapyTacrolimus (Topical): Corticosteroids (Systemic) may enhance the immunosuppressive effect of Tacrolimus (Topical).Risk X: Avoid combinationTalimogene Laherparepvec: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased.Risk X: Avoid combinationTemsirolimus: DexAMETHasone (Systemic) may decrease serum concentrations of the active metabolite(s) of Temsirolimus.Risk C: Monitor therapyTertomotide: Corticosteroids (Systemic) may diminish the therapeutic effect of Tertomotide.Risk X: Avoid combinationThalidomide: DexAMETHasone (Systemic) may enhance the dermatologic adverse effect of Thalidomide. DexAMETHasone (Systemic) may enhance the thrombogenic effect of Thalidomide.Management: Consider using venous thromboembolism prophylaxis (eg, low-molecular-weight heparin or warfarin [INR 2.0 to 3.0]) in patients with multiple myeloma receiving both thalidomide and dexamethasone. Monitor for increased dermatologic adverse effects (eg, rash) Risk D: Consider therapy modificationThiazide and Thiazide-Like Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics.Risk C: Monitor therapyTofacitinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Tofacitinib.Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive. Risk D: Consider therapy modificationTyphoid Vaccine: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Typhoid Vaccine.Risk X: Avoid combinationUbrogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Ubrogepant.Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a weak CYP3A4 inducer. Risk D: Consider therapy modificationUpadacitinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Upadacitinib.Management: Coadministration of upadacitinib with systemic corticosteroids at doses equivalent to greater than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks is not recommended. Risk D: Consider therapy modificationUrea Cycle Disorder Agents: Corticosteroids (Systemic) may diminish the therapeutic effect of Urea Cycle Disorder Agents. More specifically, Corticosteroids (Systemic) may increase protein catabolism and plasma ammonia concentrations, thereby increasing the doses of Urea Cycle Disorder Agents needed to maintain these concentrations in the target range.Risk C: Monitor therapyVaccines (Inactivated/Non-Replicating): Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating).Management: Administer vaccines at least 2 weeks prior to immunosuppressive corticosteroids if possible. If patients are vaccinated less than 14 days prior to or during such therapy, repeat vaccination at least 3 months after therapy if immunocompetence restored. Risk D: Consider therapy modificationVaccines (Live): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Live).Management: Avoid live vaccines during and for 1 month after therapy with immunosuppressive doses of corticosteroids (equivalent to prednisone > 2 mg/kg or 20 mg/day in persons over 10 kg for at least 2 weeks). Give live vaccines prior to therapy whenever possible. Risk D: Consider therapy modificationVitamin K Antagonists (eg, warfarin): Corticosteroids (Systemic) may enhance the anticoagulant effect of Vitamin K Antagonists.Risk C: Monitor therapyVoriconazole: DexAMETHasone (Systemic) may decrease the serum concentration of Voriconazole.Risk C: Monitor therapyYellow Fever Vaccine: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Yellow Fever Vaccine.Risk X: Avoid combinationDietary ConsiderationsMay be taken with meals to decrease GI upset. May need diet with increased potassium, pyridoxine, vitamin C, vitamin D, folate, calcium, and phosphorus.Reproductive ConsiderationsThe manufacturer’s labeling for use of dexamethasone as part of combination therapy for multiple myeloma recommends pregnancy testing prior to use in patients who may become pregnant. Patients who may become pregnant should use effective contraception during therapy and for at least 1 month after the last dexamethasone dose. Consult individual monographs for additional information related to pregnancy testing and contraception when combination therapy is used for multiple myeloma.Dexamethasone may alter the motility of and number of spermatozoa.Pregnancy ConsiderationsDexamethasone crosses the placenta (Brownfoot 2013); and is partially metabolized by placental enzymes to an inactive metabolite (Murphy 2007).Some studies have shown an association between first trimester systemic corticosteroid use and oral clefts or decreased birth weight; however, information is conflicting and may be influenced by maternal dose/indication for use (Lunghi 2010; Park-Wyllie 2000; Pradat 2003). Hypoadrenalism may occur in newborns following maternal use of corticosteroids during pregnancy; monitor.Dexamethasone is classified as a fluorinated corticosteroid. When systemic corticosteroids are needed in pregnancy for rheumatic disorders, nonfluorinated corticosteroids (eg, prednisone) are preferred. Chronic high doses should be avoided for the treatment of maternal disease (ACR [Sammaritano 2020]).Use of the overnight dexamethasone 1 mg suppression test for Cushing syndrome is not recommended during pregnancy due to the increased risk of false positives. In addition, dexamethasone is generally avoided for the treatment of pregnant patients with adrenal insufficiency (ES [Nieman 2008]; ESE [Luger 2021]).Antenatal corticosteroid administration promotes fetal lung maturity and is associated with the reduction of intraventricular hemorrhage, necrotizing enterocolitis, neonatal mortality, and respiratory distress syndrome. A single course of dexamethasone is recommended for patients between 24 0/7 and 33 6/7 weeks' gestation who are at risk of delivering within 7 days. This recommendation includes those with ruptured membranes or multiple gestations. A single course of dexamethasone may be considered for patients beginning at 23 0/7 weeks' gestation who are at risk of delivering within 7 days, in consultation with the family regarding resuscitation. In addition, a single course of dexamethasone may be given to patients between 34 0/7 weeks and 36 6/7 weeks who are at risk of preterm delivery within 7 days and who have not previously received corticosteroids if induction or delivery will proceed ≥24 hours and ≤7 days; delivery should not be delayed for administration of antenatal corticosteroids. Use of concomitant tocolytics is not currently recommended and administration of late preterm corticosteroids has not been evaluated in patients with intrauterine infection, multiple gestations, pregestational diabetes, or patients who delivered previously by cesarean section at term. Multiple repeat courses are not recommended. However, in patients with pregnancies less than 34 weeks' gestation at risk for delivery within 7 days and who had a course of antenatal corticosteroids >14 days prior, a single repeat course may be considered; use of a repeat course in patients with preterm prelabor rupture of membranes is controversial (ACOG 2016; ACOG 2017; ACOG 2020).Dexamethasone is used off label in the management of COVID-19. Use is recommended for hospitalized pregnant patients with COVID-19 who require mechanical ventilation, or who require supplemental oxygen without mechanical ventilation (NIH 2022). In patients who do not require dexamethasone for fetal lung maturity, or in those who have already completed a course of dexamethasone to enhance fetal lung development, treatment recommendations are available using alternative corticosteroids which have more limited placental transfer and may provide less fetal risk. A treatment algorithm is available for pregnant patients with severe or critical COVID-19 requiring corticosteroids for fetal lung maturation and those who do not (Saad 2020). The risk of severe illness from COVID-19 infection is increased in symptomatic pregnant patients compared to nonpregnant patients (ACOG 2022). Information related to the treatment of COVID-19 during pregnancy continues to emerge; refer to current guidelines for the treatment of pregnant patients.Some products contain alcohol, benzyl alcohol or sodium sulfite; use of preservative-free or alternative formulations in pregnancy is recommended.Monitoring ParametersHemoglobin, occult blood loss, blood pressure, serum potassium and glucose; intraocular pressure with systemic use >6 weeks; weight and height in children.Mechanism of ActionDexamethasone is a long-acting corticosteroid with minimal sodium-retaining potential. It decreases inflammation by suppression of neutrophil migration, decreased production of inflammatory mediators, and reversal of increased capillary permeability; suppresses normal immune response. Dexamethasone induces apoptosis in multiple myeloma cells. Dexamethasone's mechanism of antiemetic activity is unknown.Pharmaco*kinetics (Adult data unless noted)Onset of action: IV: Rapid.Immune thrombocytopenia: Oral: Initial response: 2 to 14 days; Peak response: 4 to 28 days (Neunert 2011).Duration: IV: Short.Absorption: Oral: 61% to 86% (Czock 2005).Metabolism: Hepatic.Half-life elimination:Extremely low birth-weight infants with BPD: 9.26 ± 3.34 hours (range: 5.85 to 16.1 hours) (Charles 1993).Children 4 months to 16 years: 4.34 ± 4.14 hours (range: 2.33 to 9.54 hours) (Richter 1983).Adults: Oral: 4 ± 0.9 hours (Czock 2005); IV: ~1 to 5 hours (Hochhaus 2001; Miyabo 1981; Rohdewald 1987; Tóth 1999).Time to peak, serum: Oral: 1 to 2 hours (Czock 2005); IM: ~30 to 120 minutes (Egerman 1997; Hochhaus 2001); IV: 5 to 10 minutes (free dexamethasone) (Miyabo 1981; Rohdewald 1987).Excretion: Urine (~10%) (Duggan 1975; Miyabo 1981).Pricing: USConcentrate (Dexamethasone Intensol Oral)1 mg/mL (per mL): $1.07Elixir (Dexamethasone Oral)0.5 mg/5 mL (per mL): $0.11 - $0.27Kit (DoubleDex Injection)10 mg/mL (per each): $598.00Kit (MAS Care-Pak Injection)10 mg/mL (per each): $605.00Solution (Dexamethasone Oral)0.5 mg/5 mL (per mL): $0.27Solution (Dexamethasone Sod Phosphate PF Injection)10 mg/mL (per mL): $2.10 - $8.22Solution (Dexamethasone Sodium Phosphate Injection)4 mg/mL (per mL): $0.93 - $3.4710 mg/mL (per mL): $1.49 - $1.7220 mg/5 mL (per mL): $0.21 - $1.51100 mg/10 mL (per mL): $0.48 - $1.70120 mg/30 mL (per mL): $0.39 - $1.63Tablet Therapy Pack (Dexamethasone Oral)1.5MG (21) (per each): $8.06 - $8.541.5MG (35) (per each): $8.551.5MG (51) (per each): $8.54Tablet Therapy Pack (Dxevo 11-Day Oral)1.5 mg (per each): $17.79Tablet Therapy Pack (HiDex 6-Day Oral)1.5MG (21) (per each): $33.29Tablet Therapy Pack (TaperDex 12-Day Oral)1.5MG (49) (per each): $5.68Tablet Therapy Pack (TaperDex 6-Day Oral)1.5 mg (per each): $10.801.5MG (21) (per each): $10.80Tablet Therapy Pack (TaperDex 7-Day Oral)1.5MG (27) (per each): $8.66Tablets (Dexamethasone Oral)0.5 mg (per each): $0.14 - $0.210.75 mg (per each): $0.25 - $0.271 mg (per each): $0.30 - $0.371.5 mg (per each): $0.48 - $3.702 mg (per each): $0.59 - $0.744 mg (per each): $1.19 - $1.206 mg (per each): $1.78 - $1.90Tablets (Hemady Oral)20 mg (per each): $31.31Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalAacidexam (BE);Alin (CR, DO, GT, HN, NI, PA, SV);Asiadexa (VN);Camidexon (ID);Corodex (UY);Cortyk (CL);D Cort (BD);Decadron (AE, BH, CO, CY, EC, IT, JO, KW, LB, PY, QA, SA);Decan (PH, SG);Decasone (ZA);Decdan (IN);Dectancyl (VN);Deltasone (EG);Desalark (IT);Dexa-Sine (BE);Dexacor (BD);Dexacort Forte (IL);Dexaflam (DE);Dexafree (CH, FR, PL, PT);Dexamax (PH);Dexamed (CZ, JO, RO, SG, TR);Dexamed Elixir (LK);Dexamet Solution for Injection (HK);Dexanocorten (EG);Dexasone (EG, MY);Dexazone (QA);Dexcor (BD);Dexmethsone (AU, NZ);Dexo (ET);Dexona (ET, IN);Dexona-E (LK);Dexone (ZW);Dexovit (LK);Dexsol (IE);Fortecortin (AT, BG, CH, DE, ES);Lenadex (JP);Lodexa (TH);Lodexa-5 (TH);Maradex (VE);Martapan (GB);Medicort (PE);Meradexone (BD);Metacort (PH);Methodex (LK);Millicorten (QA);Naxidex (LK);Nexadron Oftal (AR);Odeson (BD);Oftan Dexa (EE);Opnol (SE);Oradexon (CL, FI, ID, NL, PT, SA);Ordex (BD);Ronic (ET);Sonexa (BD);Spersadex (CH, DE, HK, NO, ZA);Sterodex (IL);Steron (BD);Vedex (LK);Vextasone (MY);Vherdex (PH);Visumetazone (IT);Wymesone (IN)For country code abbreviations (show table)Abouir K, Gosselin P, Guerrier S, et al. Dexamethasone exposure in normal-weight and obese hospitalized COVID-19 patients: an observational exploratory trial. Clin Transl Sci. 2022;15(7):1796-1804. doi:10.1111/cts.13297 [PubMed 35706350]Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319. [PubMed 11487763]Akahoshi S, Hasegawa Y. Steroid-induced iatrogenic adrenal insufficiency in children: a literature review. Endocrines. 2020;1(2):125-137. doi:10.3390/endocrines1020012Allan SG, Leonard RCF. Dexamethasone antiemesis and side-effects. Lancet. 1986;1(8488):1035. [PubMed 2871314]Allolio B. Extensive expertise in endocrinology. Adrenal crisis. Eur J Endocrinol. 2015;172(3):R115-R124. doi:10.1530/EJE-14-0824 [PubMed 25288693]American Academy of Pediatrics (AAP). In: Kimberlin DW, Brady MT, Jackson MA, Long SA, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics; 2018.American Academy of Pediatrics (AAP). Statement of endorsem*nt-congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency. Pediatrics. 2010; 126(5):151. Accessed October 27, 2014. http://pediatrics.aappublications.org/content/126/5/1051.extract.American Academy of Pediatrics Committee on Infectious Diseases. Dexamethasone Therapy for Bacterial Meningitis in Infants and Children. Pediatrics. 1990;86(1):130-133. [PubMed 2193301]American College of Obstetricians and Gynecologists (ACOG) Committee on Obstetric Practice. ACOG Committee Opinion No. 713: Antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol. 2017;130(2):e102-e109. doi:10.1097/AOG.0000000000002237 [PubMed 28742678]American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins–Obstetrics. ACOG Practice Bulletin No. 171: Management of preterm labor. Obstet Gynecol. 2016;128(4):e155-e164. doi:10.1097/AOG.0000000000001711 [PubMed 27661654]American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins–Obstetrics. ACOG Practice Bulletin No. 217: Prelabor rupture of membranes. Obstet Gynecol. 2020;135(3):e80‐e97. doi:10.1097/AOG.0000000000003700 [PubMed 32080050]American College of Obstetricians and Gynecologists (ACOG). COVID-19 FAQs for obstetricians-gynecologists, obstetrics. https://www.acog.org/clinical-information/physician-faqs/covid-19-faqs-for-ob-gyns-obstetrics. Accessed August 1, 2022.American College of Radiology (ACR) Committee on Drugs and Contrast Media. ACR manual on contrast media. https://www.acr.org/-/media/ACR/Files/Clinical-Resources/Contrast_Media.pdf. Published 2021. Accessed January 3, 2022.Anene O, Meert KL, Uy H, Simpson P, Sarnaik AP. Dexamethasone for the prevention of postextubation airway obstruction: a prospective, randomized, double-blind, placebo-controlled trial. Crit Care Med. 1996;24(10):1666-1669. [PubMed 8874303]Annane D, Pastores SM, Rochwerg B, et al. Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017. Crit Care Med. 2017;45(12):2078-2088. doi: 10.1097/CCM.0000000000002737. [PubMed 28938253]Arnold DM. Initial treatment of immune thrombocytopenia (ITP) in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 19, 2022.Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007:110, 176.Attal M, Richardson PG, Rajkumar SV, et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study [published correction appears in Lancet. 2019;394(10214):2072]. Lancet. 2019;394(10214):2096-2107. doi:10.1016/S0140-6736(19)32556-5 [PubMed 31735560]Bahal N, Nahata MC. The role of corticosteroids in infants and children with bacterial meningitis. DICP. 1991;25(5):542-545. [PubMed 2068839]Baldwin D, Apel J. Management of hyperglycemia in hospitalized patients with renal insufficiency or steroid-induced diabetes. Curr Diab Rep. 2013;13(1):114-120. doi:10.1007/s11892-012-0339-7 [PubMed 23090580]Based on expert opinion.Benghiat H, Sanghera P, Stange D, et al. Dexamethasone-related adrenal insufficiency in patients with brain and skull base tumours. Support Care Cancer. 2018;26(12):4031-4038. doi:10.1007/s00520-018-4264-4 [PubMed 29858690]Bernini JC, Rogers ZR, Sandler ES, et al. Beneficial effect of intravenous dexamethasone in children with mild to moderately severe acute chest syndrome complicating sickle cell disease. Blood. 1998;92:3082-3089. [PubMed 9787142]Berris KK, Repp AL, Kleerekoper M. Glucocorticoid-induced osteoporosis. Curr Opin Endocrinol Diabetes Obes. 2007;14(6):446-450. doi:10.1097/MED.0b013e3282f15407 [PubMed 17982350]Bhimraj A, Morgan RL, Shumaker AH, et al. Infectious Diseases Society of America (IDSA) guidelines on the treatment and management of patients with COVID-19. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/#toc-5. Updated June 29, 2022. Accessed August 10, 2022.Bjornson CL, Klassen TP, Williamson J, et al. A randomized trial of a single dose of oral dexamethasone for mild croup. N Engl J Med. 2004;351(13):1306-1313. [PubMed 15385657]Bonaventura A, Montecucco F. Steroid-induced hyperglycemia: An underdiagnosed problem or clinical inertia? A narrative review. Diabetes Res Clin Pract. 2018;139:203-220. doi:10.1016/j.diabres.2018.03.006 [PubMed 29530386]Bornstein SR. Predisposing factors for adrenal insufficiency. N Engl J Med. 2009;360(22):2328-2339. doi:10.1056/NEJMra0804635 [PubMed 19474430]Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(2):364-389. doi:10.1210/jc.2015-1710. [PubMed 26760044]Boumpas DT, Chrousos GP, Wilder RL, Cupps TR, Balow JE. Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann Intern Med. 1993;119(12):1198-1208. doi:10.7326/0003-4819-119-12-199312150-00007 [PubMed 8239251]Bowden SA, Henry R. Pediatric Adrenal insufficiency: Diagnosis, management, and new therapies. Int J Pediatr. 2018;2018:1739831. doi:10.1155/2018/1739831 [PubMed 30515225]Briot K, Roux C. Glucocorticoid-induced osteoporosis. RMD Open. 2015;1(1):e000014. doi:10.1136/rmdopen-2014-000014 [PubMed 26509049]Brownfoot FC, Gagliardi DI, Bain E, Middleton P, Crowther CA. Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2013;(8):CD006764. doi:10.1002/14651858.CD006764.pub3 [PubMed 23990333]Buckley L, Fuyatt G, Fink HA, et al. 2017 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheumatology. 2017;69(8):1521-1537.Buckley L, Humphrey MB. Glucocorticoid-induced osteoporosis. N Engl J Med. 2018;379(26):2547-2556. doi:10.1056/NEJMcp1800214 [PubMed 30586507]Caplan A, Fett N, Rosenbach M, Werth VP, Micheletti RG. Prevention and management of glucocorticoid-induced side effects: A comprehensive review: Gastrointestinal and endocrinologic side effects. J Am Acad Dermatol. 2017;76(1):11-16. doi:10.1016/j.jaad.2016.02.1239 [PubMed 27986133]Carney N, Totten AM, O'Reilly C, et al; Brain Trauma Foundation. Guidelines for the management of severe traumatic brain injury, fourth edition [published online September 20, 2016]. Neurosurgery. doi:10.1227/NEU.0000000000001432. [PubMed 27654000]Centeno LM, Moore ME. Preferred intraarticular corticosteroids and associated practice: a survey of members of the American College of Rheumatology. Arthritis Care Res. 1994;7(3):151-155. [PubMed 7727555]Centers for Disease Control (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm [PubMed 6810084]Chang SM, Messersmith H, Ahluwalia M, et al. Anticonvulsant prophylaxis and steroid use in adults with metastatic brain tumors: summary of SNO and ASCO endorsem*nt of the Congress of Neurological Surgeons guidelines. Neuro Oncol. 2019;21(4):424-427. doi:10.1093/neuonc/noz034. [PubMed 30883663]Chang YP. Evidence for adverse effect of perinatal glucocorticoid use on the developing brain. Korean J Pediatr. 2014;57(3):101-109. doi:10.3345/kjp.2014.57.3.101 [PubMed 24778691]Chanimov M, Koren-Michowitz M, Cohen ML, Pilipodi S, Bahar M. Tumor lysis syndrome induced by dexamethasone. Anesthesiology. 2006;105(3):633-634. doi:10.1097/00000542-200609000-00042 [PubMed 16932011]Chari A, Rodriguez-Otero P, McCarthy H, et al. Subcutaneous daratumumab plus standard treatment regimens in patients with multiple myeloma across lines of therapy (PLEIADES): an open-label phase II study. Br J Haematol. 2021;192(5):869-878. doi:10.1111/bjh.16980 [PubMed 33216361]Chari A, Suvannasankha A, Fay JW, et al. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood. 2017;130(8):974-981. doi:10.1182/blood-2017-05-785246. [PubMed 28637662]Chari A, Vogl DT, Gavriatopoulou M, et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019;381(8):727-738. doi:10.1056/NEJMoa1903455 [PubMed 31433920]Charles B, Schild P, Steer P, Cartwright D, Donovan T. Pharmaco*kinetics of dexamethasone following single-dose intravenous administration to extremely low birth weight infants. Dev Pharmacol Ther. 1993;20(3-4):205-210. [PubMed 7828455]Chen JS, Wu JM, Chen YJ, Yeh TF. Pulsed high-dose dexamethasone therapy in children with chronic idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol. 1997;19(6):526-529. [PubMed 9407939]Cinvanti (aprepitant IV) [prescribing information]. San Diego, CA: Heron Therapeutics, Inc; November 2017.Ciriaco M, Ventrice P, Russo G, et al. Corticosteroid-related central nervous system side effects. J Pharmacol Pharmacother. 2013;4(suppl 1):S94-S98. doi:10.4103/0976-500X.120975 [PubMed 24347992]Colman I, Friedman BW, Brown MD, et al. Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomised controlled trials for preventing recurrence. BMJ. 2008;336(7657):1359-1361. doi:10.1136/bmj.39566.806725.BE [PubMed 18541610]Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med. 2003;348(8):727-734. doi:10.1056/NEJMra020529. [PubMed 12594318]Coursin DB, Wood KE. Corticosteroid supplementation for adrenal insufficiency. JAMA. 2002;287(2):236-240. doi:10.1001/jama.287.2.236 [PubMed 11779267]Couser RJ, Ferrara TB, Falde B, et al. Effectiveness of dexamethasone in preventing extubation failure in preterm infants at increased risk for airway edema. J Pediatr. 1992;121(4):591-596. [PubMed 1403397]Cruz MN, Stewart G, Rosenberg N. Use of dexamethasone in the outpatient management of acute laryngotracheitis. Pediatrics. 1995;96(2 Pt 1):220-223. [PubMed 7630673]Czock D, Keller F, Rasche FM, Häussler U. Pharmaco*kinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmaco*kinet. 2005;44(1):61-98. doi:10.2165/00003088-200544010-00003 [PubMed 15634032]Davis PG and Henderson-Smart DJ. Intravenous dexamethasone for extubation of newborn infants. Cochrane Database Syst Rev. 2001;(4):CD000308. [PubMed 11687075]de Gans J, van de Beek D; European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002;347(20):1549-1556. doi:10.1056/NEJMoa021334. [PubMed 12432041]De Laet MH, Dassonville M, Johansson A, et al. Small-bowel perforation in very low birth weight neonates treated with high-dose dexamethasone. Eur J Pediatr Surg. 2000;10(5):323-327. doi:10.1055/s-2008-1072384 [PubMed 11194544]De Oliveira GS Jr, Castro-Alves LJ, Ahmad S, Kendall MC, McCarthy RJ. Dexamethasone to prevent postoperative nausea and vomiting: an updated meta-analysis of randomized controlled trials. Anesth Analg. 2013;116(1):58-74. doi:10.1213/ANE.0b013e31826f0a0a [PubMed 23223115]Decadron (dexamethasone) [prescribing information]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; May 2019.Delaleu J, Destere A, Hachon L, Declèves X, Lloret-Linares C. Glucocorticoids dosing in obese subjects: a systematic review. Therapie. 2019;74(4):451-458. doi:10.1016/j.therap.2018.11.016 [PubMed 30928086]Desandre PL, Quest TE. Management of cancer-related pain. Hematol Oncol Clin North Am. 2010;24(3):643-658. [PubMed 20488359]Dexabliss (dexamethasone) [prescribing information]. Biloxi, MS: Levins Pharmaceuticals; March 2020.Dexamethasone elixir [prescribing information]. Morton Grove, IL: Morton Grove Pharmaceuticals; April 2008.Dexamethasone, Granisetron, or Both for the Prevention of Nausea and Vomiting During Chemotherapy for Cancer. The Italian Group for Antiemetic Research. N Engl J Med. 1995;332(1):1-5. [PubMed 7990859]Dexamethasone Injection, USP (dexamethasone sodium phosphate) [prescribing information]. Lake Zurich, IL: Fresenius Kabi; November 2017.Dexamethasone Injection, USP (dexamethasone sodium phosphate) [prescribing information]. Rockford, IL: Mylan; December 2015.Dexamethasone tablets, dexamethasone oral solution, Intensol [prescribing information]. East Windsor, New Jersey: Novitium Pharma LLC; June 2022.Dexamethasone tablets and dexamethasone oral solution [prescribing information]. East Windsor, New Jersey: Novitium Pharma LLC; June 2022.DexPak 13 Day TaperPak, 10 Day TaperPak, and 6 Day TaperPak (dexamethasone) [prescribing information]. Richmond, VA: ECR; June 2011.Dickerson JE Jr, Dotzel E, Clark AF. Steroid-induced cataract: new perspective from in vitro and lens culture studies. Exp Eye Res. 1997;65(4):507-516. doi:10.1006/exer.1997.0359 [PubMed 9464184]Dietrich J, Rao K, Pastorino S, Kesari S. Corticosteroids in brain cancer patients: benefits and pitfalls. Expert Rev Clin Pharmacol. 2011;4(2):233-242. doi:10.1586/ecp.11.1 [PubMed 21666852]Dimopoulos MA, Dytfeld D, Grosicki S, et al. Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma. N Engl J Med. 2018;379(19):1811-1822. doi: 10.1056/NEJMoa1805762. [PubMed 30403938]Dimopoulos MA, Moreau P, Palumbo A, et al; ENDEAVOR Investigators. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016a;17(1):27-38. doi:10.1016/S1470-2045(15)00464-7. [PubMed 26671818]Dimopoulos MA, Oriol A, Nahi H, et al; POLLUX Investigators. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016b;375(14):1319-1331. [PubMed 27705267]Dimopoulos MA, Sonneveld P, Leung N, et al. International Myeloma Working Group recommendations for the diagnosis and management of myeloma-related renal impairment. J Clin Oncol. 2016c;34(13):1544-1557. [PubMed 26976420]Dimopoulos M, Quach H, Mateos MV, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Lancet. 2020;396(10245):186-197. doi:10.1016/S0140-6736(20)30734-0 [PubMed 32682484]Dimopoulos MA, Terpos E, Boccadoro M, et al; APOLLO Trial Investigators. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(6):801-812. doi:10.1016/S1470-2045(21)00128-5 [PubMed 34087126]Dineen R, Thompson CJ, Sherlock M. Adrenal crisis: prevention and management in adult patients. Ther Adv Endocrinol Metab. 2019;10:2042018819848218. doi:10.1177/2042018819848218 [PubMed 31223468]Dixon WG, Abrahamowicz M, Beauchamp ME, et al. Immediate and delayed impact of oral glucocorticoid therapy on risk of serious infection in older patients with rheumatoid arthritis: a nested case-control analysis. Ann Rheum Dis. 2012;71(7):1128-1133. doi:10.1136/annrheumdis-2011-200702 [PubMed 22241902]Doyle LW, Davis PG, Morley CJ, et al. Low-Dose Dexamethasone Facilitates Extubation Among Chronically Ventilator-Dependent Infants: A Multicenter, International, Randomized, Controlled Trial. Pediatrics. 2006;117(1):75-83. [PubMed 16396863]Drozdowicz LB, Bostwick JM. Psychiatric adverse effects of pediatric corticosteroid use. Mayo Clin Proc. 2014;89(6):817-834. doi:10.1016/j.mayocp.2014.01.010 [PubMed 24943696]Duggan DE, Matalia N, Ditzler, CA, et al. Bioavailability of oral dexamethasone. Clin Pharmacol Ther. 1975;18(2):205-209. [PubMed 1097154]Dulek DE, Fuhlbrigge RC, Tribble AC, et al. Multidisciplinary guidance regarding the use of immunomodulatory therapies for acute coronavirus disease 2019 in pediatric patients. J Pediatric Infect Dis Soc. 2020;9(6):716-737. doi:10.1093/jpids/piaa098 [PubMed 32808988]Dupuis LL, Boodhan S, Holdsworth M, et al; Pediatric Oncology Group of Ontario. Guideline for the prevention of acute nausea and vomiting due to antineoplastic medication in pediatric cancer patients. Pediatr Blood Cancer. 2013;60(7):1073-1082. doi:10.1002/pbc.24508. [PubMed 23512831]Durand M, Sardesai S, McEvoy C. Effects of early dexamethasone therapy on pulmonary mechanics and chronic lung disease in very low birth weight infants: a randomized, controlled trial. Pediatrics. 1995;95(4):584-590. [PubMed 7700763]Durie BGM, ho*ring A, Abidi MH, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017;389(10068):519-527. doi:10.1016/S0140-6736(16)31594-X [PubMed 28017406]Durie BGM, ho*ring A, Sexton R, et al. Longer term follow-up of the randomized phase III trial SWOG S0777: bortezomib, lenalidomide and dexamethasone vs. lenalidomide and dexamethasone in patients (Pts) with previously untreated multiple myeloma without an intent for immediate autologous stem cell transplant (ASCT). Blood Cancer J. 2020;10(5):53. doi:10.1038/s41408-020-0311-8 [PubMed 32393732]Dxevo (dexamethasone) [prescribing information]. Ocean Springs, MS: Phlight Pharma.; June 2019.Egerman RS, Pierce WF 4th, Andersen RN, Umstot ES, Carr TL, Sibai BM. A comparison of the bioavailability of oral and intramuscular dexamethasone in women in late pregnancy. Obstet Gynecol. 1997;89(2):276-280. [PubMed 9015035]Erstad BL. Dosing of medications in morbidly obese patients in the intensive care unit setting. Intensive Care Med. 2004;30(1):18-32. doi:10.1007/s00134-003-2059-6. [PubMed 14625670]Facon T, Kumar S, Plesner T, et al; MAIA Trial Investigators. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380(22):2104-2115. doi:10.1056/NEJMoa1817249. [PubMed 31141632]Facon T, Venner CP, Bahlis NJ, et al. Oral ixazomib, lenalidomide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma. Blood. 2021;137(26):3616-3628. doi:10.1182/blood.2020008787 [PubMed 33763699]Fardet L, Petersen I, Nazareth I. Suicidal behavior and severe neuropsychiatric disorders following glucocorticoid therapy in primary care. Am J Psychiatry. 2012;169(5):491-497. doi:10.1176/appi.ajp.2011.11071009 [PubMed 22764363]Fong AC, Cheung NW. The high incidence of steroid-induced hyperglycaemia in hospital. Diabetes Res Clin Pract. 2013;99(3):277-280. doi:10.1016/j.diabres.2012.12.023 [PubMed 23298665]Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi:10.1210/jc.2015-4061. [PubMed 26934393]Furst DE, Saag KG. Glucocorticoid withdrawal. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 22, 2022.Gahart BL, Nazareno AR, Ortega MQ. Gahart’s 2021 Intravenous Medications: A Handbook for Nurses and Health Professionals. 37th ed. Elsevier; 2021.Gal P, Reed M. Medications. In: Kliegman RM, Behrman RE, Jenson HB, et al, eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, PA: Saunders Elsevier; 2007: 2955-2999.Gallagher SA, Hackett P. Acute mountain sickness and high altitude cerebral edema. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 1, 2021.Gan TJ, Belani KG, Bergese S, et al. Fourth consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg. 2020;131(2):411-448. doi:10.1213/ANE.0000000000004833 [PubMed 32467512]García Rodríguez LA, Lin KJ, Hernández-Díaz S, Johansson S. Risk of upper gastrointestinal bleeding with low-dose acetylsalicylic acid alone and in combination with clopidogrel and other medications. Circulation. 2011;123(10):1108-1115. doi:10.1161/CIRCULATIONAHA.110.973008 [PubMed 21357821]George MD, Baker JF, Winthrop K, et al. Risk for serious infection with low-dose glucocorticoids in patients with rheumatoid arthritis: a cohort study. Ann Intern Med. 2020;173(11):870-878. doi:10.7326/M20-1594 [PubMed 32956604]George R, Jeba J, Ramkumar G, Chacko AG, Tharyan P. Interventions for the treatment of metastatic extradural spinal cord compression in adults. Cochrane Database Syst Rev. 2015;(9):CD006716. doi:10.1002/14651858.CD006716.pub3. [PubMed 26337716]Ghisdal L, Van Laecke S, Abramowicz MJ, Vanholder R, Abramowicz D. New-onset diabetes after renal transplantation: risk assessment and management. Diabetes Care. 2012;35(1):181-188. doi:10.2337/dc11-1230 [PubMed 22187441]Giuliana G, Marcianò V, De Cosimo D, D'Angelo M. Effetti sui tessuti parodontali di uno spazzolino a setole "ammortizzate" (Analisi al S.E.M.) [Effect on periodontal tissue of a "cushioned" bristle brush. (S.E.M. analysis)]. Stomatol Mediterr. 1990;10(2):77-82. Italian. [PubMed 2218744]Gill N, Sirizzotti N, Johnson D, et al. Endogenous glucocorticoid response to single-dose dexamethasone for croup in children: A pharmacodynamic study. Pediatr Emerg Care. 2020;36(1):50-56. doi:10.1097/PEC.0000000000001142 [PubMed 28398936]Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. Updated 2020. Accessed May 6, 2020. https://ginasthma.org/wp-content/uploads/2020/04/GINA-2020-full-report_-final-_wms.pdf.Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention.https://ginasthma.org/gina-reports/. Updated 2022. Accessed October 11, 2022.Goedert JJ, Vitale F, Lauria C, et al. Risk factors for classical Kaposi's sarcoma. J Natl Cancer Inst. 2002;94(22):1712-1718. [PubMed 12441327]Gordon P, Rutledge J, Sawin R, Thomas S, Woodrum D. Early postnatal dexamethasone increases the risk of focal small bowel perforation in extremely low birth weight infants. J Perinatol. 1999;19(8 Pt 1):573-577. doi:10.1038/sj.jp.7200269 [PubMed 10645522]Gordon PV, Young ML, Marshall DD. Focal small bowel perforation: an adverse effect of early postnatal dexamethasone therapy in extremely low birth weight infants. J Perinatol. 2001;21(3):156-160. doi:10.1038/sj.jp.7200520 [PubMed 11503101]Grosicki S, Simonova M, Spicka I, et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet. 2020;396(10262):1563-1573. doi:10.1016/S0140-6736(20)32292-3 [PubMed 33189178]Gupta P, Bhatia V. Corticosteroid physiology and principles of therapy. Indian J Pediatr. 2008;75(10):1039-1044. [PubMed 19023528]Guslandi M. Steroid ulcers: Any news? World J Gastrointest Pharmacol Ther. 2013;4(3):39-40. doi:10.4292/wjgpt.v4.i3.39 [PubMed 23919213]Hamrahian AH, Sanziana R, Milan S. The management of the surgical patient taking glucocorticoids. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 8, 2020.Haran M, Schattner A, Kozak N, Mate A, Berrebi A, Shvidel L. Acute steroid myopathy: a highly overlooked entity. QJM. 2018;111(5):307-311. doi:10.1093/qjmed/hcy031 [PubMed 29462474]Haywood A, Good P, Khan S, et al. Corticosteroids for the management of cancer-related pain in adults. Cochrane Database Syst Rev. 2015;2015(4):CD010756. doi:10.1002/14651858.CD010756.pub2 [PubMed 25908299]Hedlund-Treutiger I, Henter JI, Elinder G. Randomized study of IVIg and high-dose dexamethasone therapy for children with chronic idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol. 2003;25(2):139-44. [PubMed 12571466]Hegenbarth MA; American Academy of Pediatrics Committee on Drugs. Preparing for pediatric emergencies: drugs to consider. Pediatrics. 2008;121(2):433-443. [PubMed 18245435]Hemady (dexamethasone) [prescribing information]. East Windsor, NJ: Acrotech Biopharma Inc; July 2022.Henderson LA, Canna SW, Friedman KG, et al. American College of Rheumatology (ACR) clinical guidance for multisystem inflammatory syndrome in children associated with SARS-CoV-2 and hyperinflammation in pediatric COVID-19: Version 3. Arthritis Rheumatol. Published online February 3, 2022. doi:10.1002/art.42062 [PubMed 35118829]Hernández-Díaz S, Rodríguez LA. Steroids and risk of upper gastrointestinal complications. Am J Epidemiol. 2001;153(11):1089-1093. doi:10.1093/aje/153.11.1089 [PubMed 11390328]Hesketh PJ. Prevention and treatment of chemotherapy-induced nausea and vomiting in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 16, 2020b.Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: ASCO guideline update. J Clin Oncol. 2020a;38(24):2782-2797. doi:10.1200/JCO.20.01296 [PubMed 32658626]Hochhaus G, Barth J, al-Fayoumi S, et al. Pharmaco*kinetics and pharmacodynamics of dexamethasone sodium-m-sulfobenzoate (DS) after intravenous and intramuscular administration: a comparison with dexamethasone phosphate (DP). J Clin Pharmacol. 2001;41(4):425-434. [PubMed 11304899]Holdsworth MT, Raisch DW, Frost J. Acute and delayed nausea and emesis control in pediatric oncology patients. Cancer. 2006;106(4):931-940. [PubMed 16404740]Honoré PM, Jacobs R, De Waele E, et al. What do we know about steroids metabolism and 'PK/PD approach' in AKI and CKD especially while on RRT--current status in 2014. Blood Purif. 2014;38(2):154-157. doi:10.1159/000368390 [PubMed 25471548]Hopkins RL, Leinung MC. Exogenous Cushing's syndrome and glucocorticoid withdrawal. Endocrinol Metab Clin North Am. 2005;34(2):371-84, ix. doi:10.1016/j.ecl.2005.01.013 [PubMed 15850848]Horby P, Lim WS, Emberson J, et al. Effect of dexamethasone in hospitalized patients with COVID-19: preliminary report. Published June 22, 2020. Accessed June 25, 2020. https://www.medrxiv.org/content/10.1101/2020.06.22.20137273v1.Huang Y, Cai X, Song X, et al. Steroids for preventing recurrence of acute severe migraine headaches: a meta-analysis. Eur J Neurol. 2013;20(8):1184-1190. doi:10.1111/ene.12155 [PubMed 23577697]Husebye ES, Allolio B, Arlt W, et al. Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J Intern Med. 2014;275(2):104-115. doi:10.1111/joim.12162 [PubMed 24330030]Huscher D, Thiele K, Gromnica-Ihle E, et al. Dose-related patterns of glucocorticoid-induced side effects. Ann Rheum Dis. 2009;68(7):1119-1124. doi:10.1136/ard.2008.092163 [PubMed 18684744]Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]"Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics Committee on Drugs. Pediatrics. 1997;99(2):268-278. [PubMed 9024461]James ER. The etiology of steroid cataract. J Ocul Pharmacol Ther. 2007;23(5):403-420. doi:10.1089/jop.2006.0067 [PubMed 17900234]James HE, Madauss WC, Tibbs PA, McCloskey JJ, Bean JR. The effect of high dose dexamethasone in children with severe closed head injury. A preliminary report. Acta Neurochir (Wien). 1979;45(3-4):225-236. [PubMed 371348]Janes M, Kuster S, Goldson TM, Forjuoh SN. Steroid-induced psychosis. Proc (Bayl Univ Med Cent). 2019;32(4):614-615. doi:10.1080/08998280.2019.1629223 [PubMed 31656440]Jordan K, Roila F, Molassiotis A, et al. Antiemetics in Children Receiving Chemotherapy. MASCC/ESMO Guideline Update 2009. Support Care Cancer. 2011;19(suppl 1):S37-S42. doi: 10.1007/s00520-010-0994-7. [PubMed 20824481]Joseph RM, Hunter AL, Ray DW, Dixon WG. Systemic glucocorticoid therapy and adrenal insufficiency in adults: a systematic review. Semin Arthritis Rheum. 2016;46(1):133-141. doi: 10.1016/j.semarthrit.2016.03.001. [PubMed 27105755]Joshi GP. Anesthetic management for enhanced recovery after major surgery (ERAS) in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 31, 2022.Kale Y, Aydemir O, Ceylan O, Bas AY, Demirel N. Hypertrophic cardiomyopathy after a single dose of dexamethasone in a preterm infant. Pediatr Neonatol. 2015;56(4):268-270. doi:10.1016/j.pedneo.2013.03.015 [PubMed 23639746]Kawai S, Ichikawa Y, Homma M. Differences in metabolic properties among cortisol, prednisolone, and dexamethasone in liver and renal diseases: accelerated metabolism of dexamethasone in renal failure. J Clin Endocrinol Metab. 1985;60(5):848-854. doi:10.1210/jcem-60-5-848 [PubMed 3980669]Keeney GE, Gray MP, Morrison AK, et al. Dexamethasone for acute asthma exacerbations in children: a meta-analysis. Pediatrics. 2014;133(3):493-499. [PubMed 24515516]Khemani RG, Randolph A, Markovitz B. Corticosteroids for the prevention and treatment of post-extubation stridor in neonates, Children and Adults. Cochrane Database Syst Rev. 2009;(3):CD001000. [PubMed 19588321]Klöti J, Fanconi S, Zachmann M, Zaugg H. Dexamethasone therapy and cortisol excretion in severe pediatric head injury. Childs Nerv Syst. 1987;3(2):103-105. [PubMed 3304622]Komatsu Y, Okita K, Yuki S, et al. Open-label, randomized, comparative, phase III study on effects of reducing steroid use in combination with palonosetron. Cancer Sci. 2015;106(7):891-895. doi:10.1111/cas.12675 [PubMed 25872578]Kowal-Bielecka O, Fransen J, Avouac J, et al; EUSTAR Coauthors. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis. 2017;76(8):1327-1339. doi:10.1136/annrheumdis-2016-209909. [PubMed 27941129]Kravitz J, Dominici P, Ufberg J, Fisher J, Giraldo P. Two days of dexamethasone versus 5 days of prednisone in the treatment of acute asthma: a randomized controlled trial [published correction appears in: Ann Emerg Med. 2018;71(1):9]. Ann Emerg Med. 2011;58(2):200-204. doi:10.1016/j.annemergmed.2011.01.004. [PubMed 21334098]Kretschmer H. Prognosis of severe head injuries in childhood and adolescence. Neuropediatrics. 1983;14(3):176-181. [PubMed 6621810]Kühne T, Freedman J, Semple JW, Doyle J, Butchart S, Blanchette VS. Platelet and immune responses to oral cyclic dexamethasone therapy in childhood chronic immune thrombocytopenic purpura. J Pediatr. 1997;130(1):17-24. [PubMed 9003846]Kumar A, Weber MH, Gokaslan Z, et al. Metastatic spinal cord compression and steroid treatment: a systematic review. Clin Spine Surg. 2017;30(4):156-163. doi:10.1097/BSD.0000000000000528. [PubMed 28437329]Lam DS, Fan DS, Ng JS, Yu CB, Wong CY, Cheung AYl. Ocular hypertensive and anti-inflammatory responses to different dosages of topical dexamethasone in children: a randomized trial. Clin Experiment Ophthalmol. 2005;33(3):252-258. [PubMed 15932528]Lamiable D, Vistelle R, Sulmont V, Millart H, Caron J, Choisy H. Pharmacocinétique de la dexaméthasone par voie orale chez le sujet obèse [pharmaco*kinetics of dexamethasone administered orally in obese patients]. Therapie. 1990;45(4):311-314. [PubMed 2399513]Larocca A, Bonello F, Gaidano G, et al. Dose/schedule-adjusted Rd-R vs continuous Rd for elderly, intermediate-fit patients with newly diagnosed multiple myeloma. Blood. 2021;137(22):3027-3036. doi:10.1182/blood.2020009507 [PubMed 33739404]Laubach JP. Multiple myeloma: administrations considerations for common therapies. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 9, 2022.Leachman SA, Reed BR. The use of dermatologic drugs in pregnancy and lactation. Dermatol Clin. 2006;24(2):167-197. [PubMed 16677965]Lee MJ, Guinn D. Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 23, 2021.Leonard JM. Central nervous system tuberculosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 9, 2019.Leonard MB. Glucocorticoid-induced osteoporosis in children: impact of the underlying disease. Pediatrics. 2007;119(suppl 2):S166-S174. [PubMed 17332238]Liu D, Ahmet A, Ward L, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013;9(1):30. doi:10.1186/1710-1492-9-30 [PubMed 23947590]Loblaw DA, Mitera G, Ford M, Laperriere NJ. A 2011 updated systematic review and clinical practice guideline for the management of malignant extradural spinal cord compression. Int J Radiat Oncol Biol Phys. 2012;84(2):312-317. doi:10.1016/j.ijrobp.2012.01.014. [PubMed 22420969]Lonial S, Dimopoulos M, Palumbo A, et al; ELOQUENT-2 Investigators. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373(7):621-631. [PubMed 26035255]Loprinzi CL, Kugler JW, Sloan JA, et al. Randomized comparison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia/cachexia. J Clin Oncol. 1999;17(10):3299-3306. doi:10.1200/JCO.1999.17.10.3299 [PubMed 10506633]Luger A, Broersen LHA, Biermasz NR, et al. ESE clinical practice guideline on functioning and nonfunctioning pituitary adenomas in pregnancy. Eur J Endocrinol. 2021;185(3):G1-G33. doi:10.1530/EJE-21-0462 [PubMed 34425558]Luks AM, Auerbach PS, Freer L, et al. Wilderness Medical Society clinical practice guidelines for the prevention and treatment of acute altitude illness: 2019 update. Wilderness Environ Med. 2019;30(4S):S3-S18. [PubMed 31248818]Luks AM, McIntosh SE, Grissom CK, et al. Wilderness Medical Society consensus guidelines for the prevention and treatment of acute altitude illness. Wilderness Environ Med. 2010;21(2):146-155. [PubMed 20591379]Luks AM, McIntosh SE, Grissom CK, et al. Wilderness Medical Society practice guidelines for the prevention and treatment of acute altitude illness: 2014 update. Wilderness Environ Med. 2014;25(4)(suppl):S4-S14. doi:10.1016/j.wem.2014.06.017. [PubMed 25498261]Lunghi L, Pavan B, Biondi C, et al. Use of Glucocorticoids in Pregnancy. Curr Pharm Des. 2010;16(32):3616-3637. [PubMed 20977425]Makol A, Wright K, Amin S. Rheumatoid arthritis and pregnancy: safety considerations in pharmacological management. Drugs. 2011;71(15):1973‐1987. doi:10.2165/11596240-000000000-00000 [PubMed 21985166]Malbari F, Staggers KA, Minard CG, Weiner HL, Chintagumpala MM, Levy AS. Provider views on perioperative steroid use for patients with newly diagnosed pediatric brain tumors. J Neurooncol. 2020;147(1):205-212. [PubMed 32026434]Mathes BM, Alquire PC. Intralesional corticosteroid injection. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 18, 2019.Mazzucconi MG, Fazi P, Bernasconi S, et al. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood. 2007;109(4):1401-1407. [PubMed 17077333]McCallister A, So TY, Stewart J. Evaluation of the efficacy of a onetime injectable dexamethasone administered orally in the pediatric emergency department for asthma exacerbation. J Pediatr Pharmacol Ther. 2017;22(5):326-331. [PubMed 29042832]McDonnell M, Evans N. Upper and Lower Gastrointestinal Complications With Dexamethasone Despite H2 Antagonists. J Paediatr Child Health. 1995;31(2):152-154. [PubMed 7794619]McGoldrick E, Stewart F, Parker R, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2020;12(12):CD004454. doi:10.1002/14651858.CD004454.pub4 [PubMed 33368142]McIntosh JJ. Corticosteroid guidance for pregnancy during COVID-19 pandemic [published online April 9, 2020]. Am J Perinatol. 2020. doi:10.1055/s-0040-1709684 [PubMed 32274772]Migita K, Sasaki Y, Ishizuka N, et al. Glucocorticoid therapy and the risk of infection in patients with newly diagnosed autoimmune disease. Medicine (Baltimore). 2013;92(5):285-293. doi:10.1097/MD.0b013e3182a72299 [PubMed 23982055]Mikhael J, Ismaila N, Cheung MC, et al. Treatment of multiple myeloma: ASCO and CCO joint clinical practice guideline. J Clin Oncol. 2019;37(14):1228-1263. doi:10.1200/JCO.18.02096 [PubMed 30932732]Miyabo S, Nakamura T, Kuwazima S, Kishida S. A comparison of the bioavailability and potency of dexamethasone phosphate and sulphate in man. Eur J Clin Pharmacol. 1981;20(4):277-282. [PubMed 6273180]Mongelluzzo J, Mohamad Z, Ten Have TR, et al. Corticosteroids and Mortality in Children With Bacterial Meningitis. JAMA. 2008;299(17):2048-2055. [PubMed 18460665]Moreau P, Dimopoulos MA, Mikhael J, et al; IKEMA Study Group. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Lancet. 2021;397(10292):2361-2371. doi:10.1016/S0140-6736(21)00592-4 [PubMed 34097854]Moreau P, Masszi T, Grzasko N, et al; TOURMALINE-MM1 Study Group. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;374(17):1621-1634. doi:10.1056/NEJMoa1516282 [PubMed 27119237]Moreau P, Mateos MV, Berenson JR, et al. Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study [published correction appears in Lancet Oncol. 2018;19(8):e382]. Lancet Oncol. 2018;19(7):953-964. doi:10.1016/S1470-2045(18)30354-1. [PubMed 29866475]Murphy VE, Fittock RJ, Zarzycki PK, et al. Metabolism of Synthetic Steroids by the Human Placenta. Placenta. 2007;28(1):39-46. [PubMed 16549198]Narayanaswami P, Sanders DB, Wolfe G, et al. International consensus guidance for management of myasthenia gravis: 2020 update. Neurology. 2021;96(3):114-122. doi:10.1212/WNL.0000000000011124 [PubMed 33144515]Narum S, Westergren T, Klemp M. Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis. BMJ Open. 2014;4(5):e004587. doi:10.1136/bmjopen-2013-004587 [PubMed 24833682]National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. NIH Publication No. 08-4051. Bethesda, MD: US Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute; 2007. http://www.nhlbi.nih.gov/files/docs/guidelines/asthgdln.pdf.National Collaborating Centre for Cancer (UK). Metastatic Spinal Cord Compression: Diagnosis and Management of Patients at Risk of or with Metastatic Spinal Cord Compression. Cardiff (UK): National Collaborating Centre for Cancer (UK); November 2008. (NICE Clinical Guidelines, No. 75.) https://www.ncbi.nlm.nih.gov/books/NBK55007/. Accessed September 19, 2019. [PubMed 22171401]National Institutes of Health (NIH). Coronavirus disease (COVID-19) treatment guidelines. https://www.covid19treatmentguidelines.nih.gov. Updated September 26, 2022. Accessed September 29, 2022.Neff SPW, Stapelberg F, Warmington A. Excruciating perineal pain after intravenous dexamethasone. Anaesth Intensive Care. 2002;30(3):370-371. [PubMed 12075649]Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA; American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190-4207. [PubMed 21325604]Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829-3866. doi:10.1182/bloodadvances.2019000966 [PubMed 31794604]Ng PC. The effectiveness and side effects of dexamethasone in preterm infants with bronchopulmonary dysplasia. Arch Dis Child. 1993;68(3)(spec no):330-336. [PubMed 8466274]Nguyen TH, Tran TH, Thwaites G, et al. Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis. N Engl J Med. 2007;357(24):2431-2440. doi:10.1056/NEJMoa070852. [PubMed 18077808]Nicolaides NC, Pavlaki AN, Maria Alexandra MA, Chrousos GP. Glucocorticoid therapy and adrenal suppression. In: Feingold KR, Anawalt B, Boyce A, et al, eds. Endotext. MDText.com, Inc; October 19, 2018. [PubMed 25905379]Nieman LK. Treatment of adrenal insufficiency in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 14, 2020.Nieman LK, Biller BM, Findling JW, et al. The diagnosis of Cushing's syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2008;93(5):1526-1540. [PubMed 18334580]O'Connell MB, Fritsch MA. Musculoskeletal and connective tissue disorders. Fundamentals of Geriatric Pharmacotherapy, 2nd ed. Hutchison LC, Sleeper RB, Eds. ASHP Publications, 2015.Onland W, Offringa M, De Jaegere AP, et al. Finding the optimal postnatal dexamethasone regimen for preterm infants at risk of bronchopulmonary dysplasia: a systematic review of placebo-controlled trials. Pediatrics. 2009;123(1):367-377. [PubMed 19117904]Orr SL, Friedman BW, Christie S, et al. Management of adults with acute migraine in the emergency department: the American Headache Society evidence assessment of parenteral pharmacotherapies. Headache. 2016;56(6):911-940. doi:10.1111/head.12835 [PubMed 27300483]Ost L, Wettrell G, Bjorkhem I, et al. Prednisolone excretion in human milk. J Pediatr. 1985;106(6):1008-1011. [PubMed 3998938]Oxford University News Release. Low-cost dexamethasone reduces death by up to one third in hospitalised patients with severe respiratory complications of COVID-19. Accessed on June 18, 2020. https://www.recoverytrial.net/files/recovery_dexamethasone_statement_160620_v2final.pdf.Palumbo A, Chanan-Khan A, Weisel K, et al; CASTOR Investigators. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(8):754-766. [PubMed 27557302]Park-Wyllie L, Mazzotta P, Pastuszak A, et al. Birth defects After Maternal Exposure to Corticosteroids: Prospective Cohort Study and Meta-Analysis of Epidemiological Studies. Teratology. 2000;62(6):385-392. [PubMed 11091360]Parsons S, Tran VL. The trilogy of SARS-CoV-2 in pediatrics (part 1): acute COVID-19 in special populations. J Pediatr Pharmacol Ther. 2021;26(3):220-239. doi:10.5863/1551-6776-26.3.220 [PubMed 33833623]Pastores SM, Annane D, Rochwerg B; Corticosteroid Guideline Task Force of SCCM and ESICM. Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part II): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017. Intensive Care Med. 2018;44(4):474-477. [PubMed 29090327]Patel P, Olteanu A, Cabral S, Santesso N, Robinson PD, Dupuis LL. Dexamethasone dosing for prevention of acute chemotherapy-induced vomiting in pediatric patients: A systematic review. Pediatr Blood Cancer. 2020;67(12):e28716. doi:10.1002/pbc.28716. [PubMed 32970373]Patel P, Robinson PD, Thackray J, et al. Guideline for the prevention of acute chemotherapy-induced nausea and vomiting in pediatric cancer patients: a focused update. Pediatr Blood Cancer. 2017;64(10). doi:10.1002/pbc.26542. [PubMed 28453189]Patt H, Bandgar T, Lila A, Shah N. Management issues with exogenous steroid therapy. Indian J Endocrinol Metab. 2013;17(suppl 3):S612-S617. doi:10.4103/2230-8210.123548 [PubMed 24910822]Pelewicz K, Miśkiewicz P. Glucocorticoid withdrawal—an overview on when and how to diagnose adrenal insufficiency in clinical practice. Diagnostics (Basel). 2021;11(4):728. doi:10.3390/diagnostics11040728 [PubMed 33923971]Pereira RM, Freire de Carvalho J. Glucocorticoid-induced myopathy. Joint Bone Spine. 2011;78(1):41-44. doi:10.1016/j.jbspin.2010.02.025 [PubMed 20471889]Perron G, Dolbec P, Germain J, Béchard P. Perineal pruritus after i.v. dexamethasone administration. Can J Anaesth. 2003;50(7):749-750. [PubMed 12944454]Petrocheilou A, Tanou K, Kalampouka E, Malakasioti G, Giannios C, Kaditis AG. Viral croup: diagnosis and a treatment algorithm. Pediatr Pulmonol. 2014;49(5):421-429. [PubMed 24596395]Phillips RS, Gopaul S, Gibson F, et al. Antiemetic Medication for Prevention and Treatment of Chemotherapy Induced Nausea and Vomiting in Childhood. Cochrane Database Syst Rev. 2010;(9):CD007786. [PubMed 20824866]Phulke S, Kaushik S, Kaur S, Pandav SS. Steroid-induced glaucoma: An avoidable irreversible blindness. J Curr Glaucoma Pract. 2017;11(2):67-72. doi:10.5005/jp-journals-l0028-1226 [PubMed 28924342]Pilkey J, Streeter L, Beel A, Hiebert T, Li X. Corticosteroid-induced diabetes in palliative care. J Palliat Med. 2012;15(6):681-689. doi:10.1089/jpm.2011.0513 [PubMed 22583383]Pivonello R, Isidori AM, De Martino MC, Newell-Price J, Biller BM, Colao A. Complications of Cushing's syndrome: state of the art. Lancet Diabetes Endocrinol. 2016;4(7):611-629. doi:10.1016/S2213-8587(16)00086-3 [PubMed 27177728]Pollard AJ, Niermeyer S, Barry P, et al. Children at high altitude: An international consensus statement by an ad hoc committee of the International Society for Mountain Medicine, March 12, 2001. High Alt Med Biol. 2001;2(3):389-403. [PubMed 11682018]Poon LC, Yang H, Kapur A, et al. Global interim guidance on coronavirus disease 2019 (COVID-19) during pregnancy and puerperium from FIGO and allied partners: Information for healthcare professionals. Int J Gynaecol Obstet. 2020;149(3):273-286. doi:10.1002/ijgo.13156 [PubMed 32248521]Portenoy RK, Ahmed E, Keilson YY. Cancer pain management: role of adjuvant analgesics (coanalgesics). Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 6, 2022. [PubMed 32248521]Pradat P, Robert-Gnansia E, Di Tanna GL, et al. First trimester exposure to corticosteroids and oral clefts. Birth Defects Res A Clin Mol Teratol. 2003;67(12):968-970. [PubMed 14745915]Prete A, Bancos I. Glucocorticoid induced adrenal insufficiency. BMJ. 2021;374:n1380. doi:10.1136/bmj.n1380 [PubMed 34253540]Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019;3(22):3780-3817. doi:10.1182/bloodadvances.2019000812 [PubMed 31770441]Qureshi F, Zaritsky A, Poirier MP. Comparative efficacy of oral dexamethasone versus oral prednisone in acute pediatric asthma. J Pediatr. 2001;139(1):20-26. [PubMed 11445789]Raajasekar AKA, Barola S, Tehrani L, Chandra AB. To push or not to push: the benefit of administering anti-emetics by intravenous push. Blood. 2015;126(23):3314. https://ashpublications.org/blood/article/126/23/3314/90789/To-Push-or-Not-to-Push-The-Benefit-of.Rajkumar SV. Multiple myeloma: 2011 update on diagnosis, risk-stratification, and management [published correction appears in Am J Hematol. 2014;89(6):669]. Am J Hematol. 2011;86(1):57-65. doi:10.1002/ajh.21913. [PubMed 21181954]Rajkumar SV, Jacobus S, Callander NS, et al; Eastern Cooperative Oncology Group. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2010;11(1):29-37. doi:10.1016/S1470-2045(09)70284-0. [PubMed 19853510]Razeghinejad MR, Katz LJ. Steroid-induced iatrogenic glaucoma. Ophthalmic Res. 2012;47(2):66-80. doi:10.1159/000328630 [PubMed 21757964]RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in hospitalized patients with covid-19 - preliminary report. N Engl J Med. Published online July 17, 2020. doi:10.1056/NEJMoa2021436 [PubMed 32678530]Rehrer MW, Liu B, Rodriguez M, Lam J, Alter HJ. A randomized controlled noninferiority trial of single dose of oral dexamethasone versus 5 days of oral prednisone in acute adult asthma. Ann Emerg Med. 2016;68(5):608-613. doi:10.1016/j.annemergmed.2016.03.017 [PubMed 27117874]Richter O, Ern B, Reinhardt D, Becker B. Pharmaco*kinetics of dexamethasone in children. Pediatr Pharmacol (New York). 1983;3(3-4):329-337. [PubMed 6677878]Rittichier KK, Ledwith CA. Outpatient Treatment of Moderate Croup With Dexamethasone: Intramuscular Versus Oral Dosing. Pediatrics. 2000;106(6):1344-1348. [PubMed 11099587]Roberts WN. Intraarticular and soft tissue injections: What agent(s) to inject and how frequently? Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 26, 2019.Roeland EJ, Bohlke K, Baracos VE, et al. Management of cancer cachexia: ASCO guideline. J Clin Oncol. 2020;38(21):2438-2453. doi:10.1200/JCO.20.00611 [PubMed 32432946]Rohdewald P, Möllmann H, Barth J, Rehder J, Derendorf H. Pharmaco*kinetics of dexamethasone and its phosphate ester. Biopharm Drug Dispos. 1987;8(3):205-212. [PubMed 3593899]Roila F, Molassiotis A, Herrstedt J, et al. 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Ann Oncol. 2016;27(suppl 5):v119-v133. [PubMed 27664248]Rosiñol L, Oriol A, Rios R, et al. Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplant in multiple myeloma. Blood. 2019;134(16):1337-1345. doi:10.1182/blood.2019000241 [PubMed 31484647]Roth P, Happold C, Weller M. Corticosteroid use in neuro-oncology: an update. Neurooncol Pract. 2015;2(1):6-12. doi:10.1093/nop/npu029 [PubMed 26034636]Rottenstreich A, Wexler ID, Abu-Libdeh A, Berkun Y. Iatrogenic cushing syndrome due to intranasal dexamethasone. Clin Pediatr (Phila). 2015;54(12):1215-1257. doi:10.1177/0009922814563927 [PubMed 25533884]Roxanas MG, Hunt GE. Rapid reversal of corticosteroid-induced mania with sodium valproate: a case series of 20 patients. Psychosomatics. 2012;53(6):575-581. doi:10.1016/j.psym.2012.06.006 [PubMed 23157995]Russell KF, Liang Y, O'Gorman K, Johnson DW, Klassen TP. Glucocorticoids for croup. Cochrane Database Syst Rev. 2011;(1):CD001955. [PubMed 21249651]Russell K, Wiebe N, Saenz A, et al. Glucocorticoids for Croup. Cochrane Database Syst Rev. 2004;(1):CD001955. [PubMed 14973975]Ryken TC, McDermott M, Robinson PD, et al. The role of steroids in the management of brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol. 2010;96(1):103-114. doi:10.1007/s11060-009-0057-4 [PubMed 19957014]Saad AF, Chappell L, Saade GR, Pacheco LD. Corticosteroids in the management of pregnant patients with coronavirus disease (COVID-19). Obstet Gynecol. 2020;136(4):823-826. doi:10.1097/AOG.0000000000004103 [PubMed 32769659]Salem M, Tainsh RE Jr, Bromberg J, Loriaux DL, Chernow B. Perioperative glucocorticoid coverage. A reassessment 42 years after emergence of a problem. Ann Surg. 1994;219(4):416-425. doi:10.1097/00000658-199404000-00013 [PubMed 8161268]Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol. 2020;72(4):529‐556. doi:10.1002/art.41191 [PubMed 32090480]San Miguel J, Weisel K, Moreau P, et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14(11):1055-1066. doi:10.1016/S1470-2045(13)70380-2 [PubMed 24007748]Sexton DJ. Dexamethasone to prevent neurologic complications of bacterial meningitis in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com.Accessed September 20, 2019.Shefrin AE, Goldman RD. Use of dexamethasone and prednisone in acute asthma exacerbations in pediatric patients. Can Fam Physician. 2009;55(7):704-706. [PubMed 19602654]Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259. [PubMed 19188870]Shenoi RP, Timm N; Committee on Drugs; Committee on Pediatric Emergency Medicine. Drugs used to treat pediatric emergencies. Pediatrics. 2020;145(1):e20193450. [PubMed 31871244]Siegel MD, Siemieniuk R. Acute respiratory distress syndrome: Supportive care and oxygenation in adults. Post TW, ed. UpToDate. http://www.uptodate.com. Waltham, MA: UpToDate Inc. Accessed July 17, 2020.Singh A, Alter HJ, Zaia B. Does the addition of dexamethasone to standard therapy for acute migraine headache decrease the incidence of recurrent headache for patients treated in the emergency department? A meta-analysis and systematic review of the literature. Acad Emerg Med. 2008;15(12):1223-1233. doi:10.1111/j.1553-2712.2008.00283.x [PubMed 18976336]Singh M, Sharma CS, Rautela RS, Taneja A. Intravenous dexamethasone causes perineal pain and pruritus. J Anesthe Clinic Res. 2011;4:273. doi:10.4172/2155-6148.1000273 http://www.omicsonline.org/intravenous-dexamethasone-causes-perineal-pain-and-pruritus-2155-6148.1000273.pdf .Society for Maternal Fetal Medicine (SMFM) and the Society for Obstetric Anesthesia and Perinatology (SOAP). Revise Labor and Delivery COVID-19 Considerations (April 14, 2020; updated from an earlier version on March 27, 2020). Accessed April 17, 2020. https://www.smfm.org/covidclinical.Sonneveld P, Schmidt-Wolf IG, van der Holt B, et al. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012;30(24):2946-2955. doi:10.1200/JCO.2011.39.6820 [PubMed 22802322]Sparrow A, Geelhoed G. Prednisolone Versus Dexamethasone in Croup: A Randomised Equivalence Trial. Arch Dis Child. 2006;91(7):580-583. [PubMed 16624882]Speiser PW, Arlt W, Auchus RJ, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(11):4043-4088. doi:10.1210/jc.2018-01865 [PubMed 30272171]Speiser PW, Azziz R, Baskin LS, et al; Endocrine Society. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline [published correction appear in J Clin Endocrinol Metab. 2010;95(11):5137]. J Clin Endocrinol Metab. 2010;95(9):4133-4160. doi:10.1210/jc.2009-2631 [PubMed 20823466]Stark AR, Carlo WA, Tyson JE, et al; National Institute of Child Health and Human Development Neonatal Research Network. Adverse effects of early dexamethasone treatment in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med. 2001;344(2):95-101. doi:10.1056/NEJM200101113440203 [PubMed 11150359]Steen VD, Medsger TA Jr. Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis. Arthritis Rheum. 1998;41(9):1613-1619. doi:10.1002/1529-0131(199809)41:9<1613::AID-ART11>3.0.CO;2-O [PubMed 9751093]Sterne JAC, Murthy S, Diaz, JV; et al. World Health Organization (WHO) Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA. Published online September 2, 2020. doi:10.1001/jama.2020.17023 [PubMed 32876694]Stewart AK, Rajkumar SV, Dimopoulos MA, et al; ASPIRE Investigators. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372(2):142-152. doi:10.1056/NEJMoa1411321. [PubMed 25482145]Sturdza A, Millar BA, Bana N, et al. The use and toxicity of steroids in the management of patients with brain metastases. Support Care Cancer. 2008;16(9):1041-1048. doi:10.1007/s00520-007-0395-8 [PubMed 18256860]Tamez-Pérez HE, Quintanilla-Flores DL, Rodríguez-Gutiérrez R, González-González JG, Tamez-Peña AL. Steroid hyperglycemia: Prevalence, early detection and therapeutic recommendations: A narrative review. World J Diabetes. 2015;6(8):1073-1081. doi:10.4239/wjd.v6.i8.1073 [PubMed 26240704]TaperDex (dexamethasone) [prescribing information]. Ridgeland, MS: Xspire Pharma; February 2020.Tellez DW, Galvis AG, Storgion SA, et al. Dexamethasone in the Prevention of Postextubation Stridor in Children. J Pediatr. 1991;118(2):289-294. [PubMed 1993963]Thwaites GE, Nguyen DB, Nguyen HD, et al. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. N Engl J Med. 2004;351(17):1741-1751. [PubMed 15496623]Tóth GG, Kloosterman C, Uges DR, Jonkman MF. Pharmaco*kinetics of high-dose oral and intravenous dexamethasone. Ther Drug Monit. 1999;21(5):532-535. [PubMed 10519450]Trang G, Steele R, Baron M, Hudson M. Corticosteroids and the risk of scleroderma renal crisis: a systematic review. Rheumatol Int. 2012;32(3):645-653. doi:10.1007/s00296-010-1697-6 [PubMed 21132302]Tseng CL, Chen YT, Huang CJ, et al. Short-term use of glucocorticoids and risk of peptic ulcer bleeding: a nationwide population-based case-crossover study. Aliment Pharmacol Ther. 2015;42(5):599-606. doi:10.1111/apt.13298 [PubMed 26096497]Tuca A, Jimenez-Fonseca P, Gascón P. Clinical evaluation and optimal management of cancer cachexia. Crit Rev Oncol Hematol. 2013;88(3):625-636. doi:10.1016/j.critrevonc.2013.07.015 [PubMed 23953794]Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39(9):1267-1284. [PubMed 15494903]University of Oxford. RECOVERY Trial. Accessed July 8, 2020. https://www.recoverytrial.net/.Urban RC Jr, Cotlier E. Corticosteroid-induced cataracts. Surv Ophthalmol. 1986;31(2):102-110. doi:10.1016/0039-6257(86)90077-9 [PubMed 3541262]US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Updated March 2019. Accessed April 8, 2019. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf.van Staa TP, Cooper C, Leufkens HG, Bishop N. Children and the risk of fractures caused by oral corticosteroids. J Bone Miner Res. 2003;18(5):913-918. doi:10.1359/jbmr.2003.18.5.913 [PubMed 12733732]van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int. 2002;13(10):777-787. doi:10.1007/s001980200108 [PubMed 12378366]Vecht CJ, Hovestadt A, Verbiest HB, van Vliet JJ, van Putten WL. Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain tumors: a randomized study of doses of 4, 8, and 16 mg per day. Neurology. 1994;44(4):675-680. doi:10.1212/wnl.44.4.675 [PubMed 8164824]Villar J, Ferrando C, Martínez D, et al; dexamethasone in ARDS network. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med. 2020;8(3):267-276. doi:10.1016/S2213-2600(19)30417-5 [PubMed 32043986]Wald ER, Kaplan SL, Mason, EO Jr. Dexamethasone therapy for children with bacterial meningitis. Pediatrics. 1995;95(1):21-28. [PubMed 7770303]Wallace MD, Metzger NL. Optimizing the treatment of steroid-induced hyperglycemia. Ann Pharmacother. 2018;52(1):86-90. doi:10.1177/1060028017728297 [PubMed 28836444]Wang JJ, Ho ST, Lee SC, Liu YC, Ho CM. The use of dexamethasone for preventing postoperative nausea and vomiting in females undergoing thyroidectomy: a dose-ranging study. Anesth Analg. 2000a;91(6):1404-1407. doi:10.1097/00000539-200012000-00019 [PubMed 11093989]Wang JJ, Ho ST, Tzeng JI, Tang CS. The effect of timing of dexamethasone administration on its efficacy as a prophylactic antiemetic for postoperative nausea and vomiting. Anesth Analg. 2000b;91(1):136-139. doi:10.1097/00000539-200007000-00025 [PubMed 10866900]Warrington TP, Bostwick JM. Psychiatric adverse effects of corticosteroids. Mayo Clin Proc. 2006;81(10):1361-1367. doi:10.4065/81.10.1361 [PubMed 17036562]Watterberg KL; American Academy of Pediatrics. Committee on Fetus and Newborn. Policy Statement--Postnatal Corticosteroids to Prevent or Treat Bronchopulmonary Dysplasia. Pediatrics. 2010;126(4):800-808. [PubMed 20819899]Wei Y, Ji XB, Wang YW, et al. High-dose dexamethasone vs prednisone for treatment of adult immune thrombocytopenia: a prospective multicenter randomized trial. Blood. 2016;127(3):296-302. [PubMed 26480931]Widdifield J, Bernatsky S, Paterson JM, et al. Serious infections in a population-based cohort of 86,039 seniors with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2013;65(3):353-361. doi:10.1002/acr.21812 [PubMed 22833532]Winthrop KL. Infections and biologic therapy in rheumatoid arthritis: our changing understanding of risk and prevention. Rheum Dis Clin North Am. 2012;38(4):727-745. doi:10.1016/j.rdc.2012.08.019 23137579. [PubMed 23137579]World Health Organization (WHO). Breastfeeding and maternal medication, recommendations for drugs in the eleventh WHO model list of essential drugs. 2002. https://apps.who.int/iris/handle/10665/62435.World Health Organization (WHO). Corticosteroids for COVID-19: living guidance. Published September 2, 2020. Accessed September 4, 2020. https://www.who.int/publications/i/item/WHO-2019-nCoV-Corticosteroids-2020.1World Health Organization (WHO). Guidelines for treatment of drug-susceptible tuberculosis and patient care: 2017 update. Published 2017. Accessed April 9, 2019. https://apps.who.int/iris/bitstream/handle/10665/255052/9789241550000-eng.pdf;jsessionid=DE537F54942A5274CE53BA18E0FBCC15?sequence=1Yale SH, Limper AH. Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illness and prior corticosteroid therapy. Mayo Clin Proc. 1996;71(1):5-13. doi:10.4065/71.1.5 [PubMed 8538233]Yanovski JA, Cutler GB Jr, Chrousos GP, Nieman LK. Corticotropin-releasing hormone stimulation following low-dose dexamethasone administration. A new test to distinguish Cushing's syndrome from pseudo-Cushing's states. JAMA. 1993;269(17):2232-2238. [PubMed 8386285]Yildirim ZK, Büyükavci M, Eren S, Orbak Z, Sahin A, Karakelleoğlu C. Late side effects of high-dose steroid therapy on skeletal system in children with idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol. 2008;30(10):749-753. doi:10.1097/MPH.0b013e318180bbc9 [PubMed 19011472]Younes AK, Younes NK. Recovery of steroid induced adrenal insufficiency. Transl Pediatr. 2017;6(4):269-273. doi:10.21037/tp.2017.10.01 [PubMed 29184808]Youssef J, Novosad SA, Winthrop KL. Infection risk and safety of corticosteroid use. Rheum Dis Clin North Am. 2016;42(1):157-176, ix-x. doi:10.1016/j.rdc.2015.08.004 [PubMed 26611557]Zar T, Graeber C, Perazella MA. Recognition, treatment, and prevention of propylene glycol toxicity. Semin Dial. 2007;20(3):217-219. [PubMed 17555487]Topic 15964 Version 623.0

CloseSpironolactone: Drug informationSpironolactone: Drug information(For additional information see "Spironolactone: Patient drug information" and see "Spironolactone: Pediatric drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USAldactone;CaroSpirBrand Names: CanadaAldactone;JAMP-Spironolactone;MINT-Spironolactone;TEVA-SpironolactonePharmacologic CategoryAntihypertensive;Diuretic, Potassium Sparing;Mineralocorticoid (Aldosterone) Receptor AntagonistDosing: AdultNote: Suspension is not therapeutically equivalent to tablets. Suspension results in 15% to 37% higher serum concentration compared to tablets. Doses of suspension >100 mg may result in higher than expected serum concentrations. In patients requiring >100 mg/dose, use tablets only.Acne vulgaris, females, moderate to severeAcne vulgaris, females, moderate to severe (alternative agent) (off-label use): Tablet: Oral: Initial: 25 to 50 mg/day in 1 to 2 divided doses; titrate as needed based on response and tolerability to a usual effective dose of 50 to 100 mg/day in 1 to 2 divided doses; maximum dose: 200 mg/day (Ref).Ascites due to cirrhosisAscites due to cirrhosis:Note: Generally used in combination with furosemide, but may be used as monotherapy for patients with hypokalemia. For combination therapy, a dosing ratio of spironolactone 100 mg to furosemide 40 mg should generally be maintained, but can be adjusted for electrolyte abnormalities (Ref).Tablet: Oral: Initial: 100 mg once daily; titrate every 3 to 5 days based on response and tolerability; usual maximum dose: 400 mg once daily (Ref). For small-volume ascites in patients who weigh ≤50 kg, some experts recommend a starting dose of 50 mg once daily (Ref).Heart failureHeart failure:Note: When initiating therapy, verify the following: serum creatinine ≤2.5 mg/dL in men and ≤2 mg/dL in women or eGFR >30 mL/minute/1.73 m2 and serum potassium <5 mEq/L. Monitor closely and if patient develops hyperkalemia (serum potassium >5 mEq/L), reduce the dose, change to every-other-day dosing, or discontinue therapy; assess for other causes of hyperkalemia before permanent discontinuation. If renal function worsens, consider dose reduction or discontinuation (Ref).Heart failure with preserved ejection fraction (off-label use):Note: For use in patients with symptomatic heart failure with preserved ejection fraction (HFpEF) (≥45%) who have an elevated serum natriuretic peptide level or have been hospitalized for heart failure in the last 12 months (Ref). Some experts are more conservative regarding serum potassium for patients with HFpEF. They recommend initiating therapy or uptitrating the dose only if serum potassium is ≤4.7 mEq/L and eGFR is ≥30 mL/minute/1.73 m2. They recommend dose reduction or discontinuation if serum potassium is >5 mEq/L (Ref).Tablet: Oral: Initial: 12.5 mg once daily; may double the dose every 2 to 4 weeks if serum potassium and renal function are stable, up to a maximum target dose of 50 mg/day in 1 or 2 divided doses (Ref).Heart failure with reduced ejection fraction: Note: Should be considered for use in patients with symptomatic (New York Heart Association class II to IV) heart failure with reduced ejection fraction (HFrEF) (≤35%) as part of an optimal medical regimen for HFrEF (Ref).Tablet: Oral: Initial: 12.5 to 25 mg once daily; may double the dose every 4 weeks if serum potassium remains <5 mEq/L and renal function is stable, up to a maximum target dose of 50 mg/day in 1 to 2 divided doses (Ref).Suspension: Oral: Initial: 10 to 20 mg once daily. Consider a starting dose of 10 mg once daily in patients at increased risk of hyperkalemia. May titrate to 37.5 mg once daily if serum potassium remains <5 mEq/L and renal function is stable (Ref).Post-myocardial infarction, complicated by reduced ejection fraction (off-label use):Note: Should be considered for use following acute myocardial infarction (MI) in patients with left ventricular ejection fraction ≤40% plus symptoms of heart failure or diabetes. Use in addition to other pharmacologic therapies post MI (Ref).Tablet: Oral: Initial: 12.5 to 25 mg once daily; may double the dose every 4 weeks if serum potassium remains <5 mEq/L and renal function is stable, up to a maximum target dose of 50 mg/day in 1 to 2 divided doses (Ref).Suspension: Oral: Initial: 10 to 20 mg once daily. Consider a starting dose of 10 mg once daily in patients at increased risk of hyperkalemia. May titrate to 37.5 mg once daily if serum potassium remains <5 mEq/L and renal function is stable (Ref).Hirsutism, femalesHirsutism, females (alternative agent) (off-label use): Note: Typically given in addition to oral contraceptives (OCs) if inadequate response to OCs is observed after 6 months. May be considered as initial therapy for females who cannot conceive or who are using reliable contraception (Ref).Tablet: Oral: Initial: 50 mg twice daily; may increase to 100 mg twice daily as needed. Assess response at 6-month intervals before adjusting dose, adding additional agents, or switching to alternative therapy (Ref).Hormone therapy for transgender females, assigned male at birthHormone therapy for transgender females, assigned male at birth (adjunctive agent) (off-label use): Tablet: Oral: Initial: 25 mg once or twice daily in combination with other appropriate agents. Increase at 1-week intervals based on response and tolerability to a usual dose of 100 to 300 mg/day in 2 divided doses; maximum dose: 400 mg/day. Adjust dose with a goal of suppressing serum testosterone levels into the normal range for females (<50 ng/dL) (Ref).Hypertension, chronicHypertension, chronic (alternative agent):Note: Not recommended for initial management but may be considered as additional therapy for resistant hypertension in patients who do not respond adequately to combination therapy with preferred agents (Ref).Tablet: Oral: Initial: 25 mg once daily; titrate as needed after ~2 to 4 weeks based on response and tolerability up to 100 mg once daily (Ref). Some experts recommend a starting dose of 12.5 mg once daily and generally do not exceed 50 mg once daily in the absence of primary aldosteronism (Ref). Patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication titration within 1 week (Ref).Suspension: Oral: Initial: 20 mg/day in 1 or 2 divided doses; titrate as needed after ~2 to 4 weeks based on response and tolerability up to 75 mg/day in 1 or 2 divided doses. Patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication titration within 1 week (Ref).Primary aldosteronismPrimary aldosteronism:Tablet: Oral: Initial: 12.5 to 25 mg once daily (Ref); gradually titrate to the lowest effective dose; usual maximum dose: 400 mg/day (Ref). For surgical candidates, the last dose should be administered the day of surgery; discontinue spironolactone on postoperative day 1 (Ref).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultThe renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.Note: Use with caution; monitor potassium prior to initiating spironolactone and closely during therapy. In circ*mstances where treatment with spironolactone is considered necessary, interventions such as dietary counseling on a low potassium diet, loop diuretics, sodium bicarbonate to correct metabolic acidosis, and prescribing daily GI cation exchangers (eg, patiromer, zirconium cyclosilicate) have been utilized (Ref).Altered kidney function:Tablet:Ascites due to cirrhosis; hypertension; primary aldosteronism: There are no specific dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.Heart failure:eGFR >50 mL/minute/1.73 m2: No initial dosage adjustment necessary.eGFR 30 to 50 mL/minute/1.73 m2: Initial: 12.5 mg once daily or every other day; may double the dose every 4 weeks if serum potassium remains <5 mEq/L and renal function is stable, up to a maximum target dose of 25 mg/day (Ref).eGFR <30 mL/minute/1.73 m2: Use not recommended (Ref); heart failure clinical trials excluded patients with serum creatinine ≥2.5 mg/dL (Ref).Suspension:Ascites due to cirrhosis; hypertension: There are no dosage adjustments provided in the manufacturer's labeling.Heart failure:eGFR >50 mL/minute/1.73 m2: No initial dosage adjustment necessary.eGFR 30 to 50 mL/minute/1.73 m2: Initial: 10 mg once daily.eGFR <30 mL/minute/1.73 m2: Use not recommended (Ref); heart failure clinical trials excluded patients with serum creatinine ≥2.5 mg/dL (Ref).Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzed (Ref):Tablet: Not routinely recommended, but 2 small trials have demonstrated the safety of spironolactone in patients with end-stage kidney disease receiving dialysis (Ref), with a suggested maximum of 25 mg once daily (Ref). Start at lowest initial dose (eg, 12.5 mg daily or every other day) and only utilize if benefits outweigh the risks, potassium is well-controlled, and patients can be monitored closely for hyperkalemia (Ref).Peritoneal dialysis: Unlikely to be significantly dialyzed given high degree of protein binding (Ref):Tablet: Not routinely recommended, but 2 small trials have demonstrated the safety of doses up to 25 mg once daily in patients receiving peritoneal dialysis (Ref). Start at lowest initial dose (eg, 12.5 mg daily or every other day) and only utilize if benefits outweigh the risks, potassium is well-controlled, and patients can be monitored closely for hyperkalemia (Ref).Dosing: Hepatic Impairment: AdultThere are no specific dosage adjustments provided in the manufacturer's labeling; initiate with low dose and titrate slowly (cirrhosis). Use with caution; minor alterations of fluid and electrolyte balance may precipitate hepatic coma.Dosing: Pediatric(For additional information see "Spironolactone: Pediatric drug information")Note: Although spironolactone is commercially available in a suspension, it is NOT therapeutically equivalent to the tablets; commercially available suspension results in 15% to 37% higher serum concentration compared to the tablet; pediatric dosing is based on experience with tablets and extemporaneously compounded suspension. Multiple concentrations of oral suspension exist; use extra precaution and prescribe in mg (not mL).Bronchopulmonary dysplasiaBronchopulmonary dysplasia (BPD): Limited data available; efficacy results variable. Although the benefits of diuretic therapy in the management of BPD are variable (eg, optimal duration of therapy, impact on pulmonary endpoints), diuretics continue to be used in clinical practice (Ref). Infants: Oral: 1.5 mg/kg/dose every 12 hours (Ref).EdemaEdema (diuresis): Limited data available: Infants, Children, and Adolescents: Oral: Initial: 1 to 3 mg/kg/day divided every 6 to 24 hours; titrate as needed; reported maximum daily dose range: 4 to 6 mg/kg/day in divided doses every 6 to 12 hours or 400 mg/day, whichever is less (Ref)HypertensionHypertension: Limited data available: Infants, Children, and Adolescents: Oral: Initial: 1 mg/kg/day divided every 12 to 24 hours; titrate as needed up to a maximum daily dose: 3.3 mg/kg/day or 100 mg/day, whichever is less (Ref)Primary aldosteronism, treatmentPrimary aldosteronism (caused by adrenal hyperplasia), treatment: Limited data available: Infants, Children, and Adolescents: Oral: 1 to 3 mg/kg/day; maximum daily dose: 100 mg/day (Ref)Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricThere are no dosage adjustments provided in the manufacturer's labeling; spironolactone is substantially excreted by the kidney; use with caution; monitor serum potassium closely. The following recommendations have been suggested: In pediatric patients with mild to moderate failure, consider extended dosing interval (eg, every 12 to 24 hours) and avoid use in severe renal impairment (Ref).Dosing: Hepatic Impairment: PediatricThere are no dosage adjustments provided in the manufacturer's labeling. Use with caution; minor alterations of fluid and electrolyte balance may precipitate hepatic coma.Dosing: Older AdultHeart failure: Oral: Avoid use of tablets >25 mg/day (or equivalent dose of suspension) (Ref).Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Suspension, Oral: CaroSpir: 25 mg/5 mL (5 mL) [contains saccharin sodium]CaroSpir: 25 mg/5 mL (118 mL, 473 mL) [contains saccharin sodium; banana flavor]Tablet, Oral: Aldactone: 25 mgAldactone: 50 mg, 100 mg [scored]Generic: 25 mg, 50 mg, 100 mgGeneric Equivalent Available: USMay be product dependentDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Tablet, Oral: Aldactone: 25 mg, 100 mgGeneric: 25 mg, 100 mgAdministration: AdultOral:Tablet: Administer with or without food; however, administer consistently with respect to food.Suspension: Shake well before administering dose. Administer with or without food; however, administer consistently with respect to food.Administration: PediatricOral: May be taken with or without food; however, consistent administration with or without food is preferred to minimize fluctuations in drug exposure.Hazardous Drugs Handling ConsiderationsHazardous agent (NIOSH 2016 [group 2]).Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.NIOSH recommends single gloving for administration of intact tablets or capsules. If manipulating tablets/capsules (eg, to prepare an oral suspension), NIOSH recommends double gloving, a protective gown, and preparation in a controlled device; if not prepared in a controlled device, respiratory and eye/face protection as well as ventilated engineering controls are recommended. NIOSH recommends double gloving, a protective gown, and (if there is a potential for vomit or spit up) eye/face protection for administration of an oral liquid/feeding tube administration (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).Use: Labeled IndicationsAscites due to cirrhosis: Management of edema in cirrhosis of the liver unresponsive to fluid and sodium restriction.Heart failure with reduced ejection fraction: To increase survival, manage edema, and reduce need for hospitalization in patients with heart failure with reduced ejection fraction and New York Heart Association class III to IV symptoms; usually administered in conjunction with other heart failure therapies.Hypertension, chronic: Management of hypertension unresponsive to other therapies.Primary hyperaldosteronism (tablet only): Short-term preoperative treatment of primary hyperaldosteronism; long-term maintenance therapy for patients with discrete aldosterone-producing adrenal adenomas who are not candidates for surgery; long-term maintenance therapy for bilateral micro- or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism).Use: Off-Label: AdultAcne vulgaris, females, moderate to severe; Heart failure with preserved ejection fraction; Heart failure with reduced ejection fraction (New York Heart Association class II); Hirsutism, females; Hormone therapy for transgender females (assigned male at birth); Post myocardial infarction, complicated by reduced ejection fractionMedication Safety IssuesSound-alike/look-alike issues:Aldactone may be confused with Aldactazide.Older Adult: High-Risk Medication:Beers Criteria: Diuretics (spironolactone) are identified in the Beers Criteria as potentially inappropriate medications to be used with caution in patients 65 years and older due to the potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium concentration closely when initiating or adjusting the dose in older adults (Beers Criteria [AGS 2019]).International issues:Aldactone: Brand name for spironolactone [US, Canada, multiple international markets], but also the brand name for potassium canrenoate [Austria, Czech Republic, Germany, Hungary, Poland].Aldactone [US, Canada, multiple international markets] may be confused with Aldomet brand name for methyldopa [multiple international markets].Adverse Reactions (Significant): ConsiderationsGynecomastiaSpironolactone may cause gynecomastia in patients of any age that may affect one or both breasts (typically both) (Ref). Gynecomastia is usually reversible following discontinuation of therapy (Ref). Eplerenone, which is associated with a lower risk of gynecomastia, may be considered if continued aldosterone antagonist therapy is required (Ref).Mechanism: Dose- and time-related; due to decreased androgen production, inhibition of androgen receptor binding, displacement of estradiol from sex hormone-binding globulin and enhanced peripheral conversion of testosterone to estradiol (Ref).Onset: Delayed; may occur after 1 to 2 months to over a year of therapyRisk factors:• Higher doses (eg, ≥150 mg/day) (Ref)• Longer duration of therapy (Ref)HyperkalemiaSpironolactone may cause reversible hyperkalemia, which may result in hospitalization and in some cases death (Ref).Mechanism: Dose-related; related to the pharmacologic action. Competes with aldosterone for binding to the mineralocorticoid receptor, thereby inhibiting the exchange of sodium for potassium in the distal convoluted renal tubule and preventing potassium excretion.Onset: Intermediate; usually occurs within 4 weeks of initiation or dose titration (Ref).Risk factors:• Older age (Ref)• Kidney impairment (Ref)• Excessive potassium intake (eg, potassium supplements, potassium-containing salt substitutes)• Concomitant use of certain drugs (eg, angiotensin-converting enzyme [ACE] inhibitors, angiotensin-receptor blockers, drospirenone, nonsteroidal anti-inflammatory drugs) (Ref). Concurrent use of larger doses of ACE inhibitors (eg, lisinopril ≥10 mg daily in adults) also increases risk (Ref).• Heart failure (especially patients receiving higher doses and patients with diabetes mellitus, higher baseline serum potassium levels, and worse New York Heart Association functional class) (Ref)Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.1% to 10%: Endocrine & metabolic: Gynecomastia (9%; up to 52% in patients receiving high doses [eg, ≥150 mg/day]) (Haynes 2009; Jeunemaitre 1987; Nuttall 2015; Prisant 2005)Frequency not defined:Cardiovascular: VasculitisDermatologic: Chloasma, erythematous maculopapular rash, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticariaEndocrine & metabolic: Amenorrhea (Levitt 1970), decreased libido, hyperglycemia, hypocalcemia, hypomagnesemia, hyponatremia, hypovolemiaGastrointestinal: Abdominal cramps, diarrhea, gastritis, gastrointestinal hemorrhage, gastrointestinal ulcer, nausea, vomitingGenitourinary: Erectile dysfunction, irregular menses, mastalgia, postmenopausal bleedingHematologic & oncologic: Agranulocytosis (Whitling 1997), leukopenia, thrombocytopeniaHepatic: HepatotoxicityHypersensitivity: AnaphylaxisImmunologic: Drug reaction with eosinophilia and systemic symptomsNervous system: Ataxia, confusion, dizziness, drowsiness, headache, lethargy, nipple painNeuromuscular & skeletal: Lower limb crampRenal: Renal failure syndrome, renal insufficiencyMiscellaneous: FeverPostmarketing: Endocrine & metabolic: Gout (Ben Salem 2017), hyperkalemia (common: ≥10%) (Huang 2005; Shah 2005), hyperuricemia (Ben Salem 2017), metabolic acidosis (in patients with cirrhosis) (Feinfeld 1978; Gabow 1979), ovarian cyst (in a premature neonate) (Vachharajani 2001)ContraindicationsHyperkalemia; Addison disease; concomitant use with eplerenone.Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to spironolactone or any component of the formulation; acute renal insufficiency; severe renal impairment (eGFR <30 mL/minute/1.73 m2); anuria; concomitant use with heparin or low molecular weight heparin; pregnancy; breastfeeding.Warnings/PrecautionsConcerns related to adverse effects:• Fluid/electrolyte imbalance: Fluid and electrolyte imbalance (eg, hypomagnesemia, hyponatremia, hypocalcemia, hyperglycemia, hyperkalemia) may occur. Patients with heart failure, renal disease, or cirrhosis may be particularly susceptible. Monitor and correct electrolyte disturbances; adjust dose to avoid dehydration.• Tumorigenic: Shown to be a tumorigen in chronic toxicity animal studies. Recent retrospective and observational studies do not suggest an increased risk of prostate or breast cancer (McKenzie 2016; Rozner 2020; Sabatier 2019).Disease-related concerns:• Adrenal vein catheterization: Discontinue use prior to adrenal vein catheterization.• Heart failure: When evaluating a heart failure patient for spironolactone treatment, eGFR should be >30 mL/minute/1.73 m2 or creatinine should be ≤2.5 mg/dL (men) or ≤2 mg/dL (women) with no recent worsening and potassium <5 mEq/L with no history of severe hyperkalemia (ACCF/AHA [Yancy 2013]). Serum potassium levels require close monitoring and management if elevated. American College of Cardiology/American Heart Association recommends considering discontinuation upon the development of serum potassium >5.5 mEq/L or worsening renal function with careful evaluation of the entire medical regimen. Avoid triple therapy with the combined use of an ACE inhibitor, ARB, and spironolactone. Therapy may need to be modified during an episode of diarrhea or dehydration or when loop diuretic therapy is interrupted (ACCF/AHA [Yancy 2013]).Special populations:• Older adult: Avoid use of tablets >25 mg/day in older adult patients with heart failure or with reduced renal function (eg, CrCl <30 mL/minute or eGFR ≤30 mL/minute/1.73 m2 [ACCF/AHA (Yancy 2013)]).Other warnings/precautions:• Suspension: Suspension is NOT therapeutically equivalent to tablets. In patients requiring >100 mg/dose, use tablets (>100 mg/dose of suspension may result in spironolactone concentration higher than expected).Metabolism/Transport EffectsNone known.Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Abiraterone Acetate: Spironolactone may diminish the therapeutic effect of Abiraterone Acetate.Risk C: Monitor therapyAlfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyAlpha-/Beta-Agonists: Spironolactone may diminish the vasoconstricting effect of Alpha-/Beta-Agonists.Risk C: Monitor therapyAmifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine.Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modificationAMILoride: May enhance the hyperkalemic effect of Spironolactone. Risk X: Avoid combinationAmmonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis.Risk C: Monitor therapyAmphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapyAngiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapyAngiotensin-Converting Enzyme Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors.Risk C: Monitor therapyAntipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]).Risk C: Monitor therapyAspirin: May diminish the therapeutic effect of Spironolactone. Risk C: Monitor therapyAtorvastatin: May enhance the adverse/toxic effect of Spironolactone. Specifically, there is a theoretical potential for enhanced effects on reducing endogenous steroid activity. Risk C: Monitor therapyBarbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyBenperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyBrigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapyBrimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyBromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combinationCholestyramine Resin: May enhance the adverse/toxic effect of Spironolactone. Specifically, the risks of developing metabolic acidosis and hyperkalemia may be elevated with this combination. Risk C: Monitor therapyCiprofloxacin (Systemic): Spironolactone may enhance the arrhythmogenic effect of Ciprofloxacin (Systemic).Risk C: Monitor therapyCosyntropin: Spironolactone may diminish the diagnostic effect of Cosyntropin.Management: Patients receiving spironolactone should omit their pre-test dose on the day selected for cosyntropin testing. Risk D: Consider therapy modificationCycloSPORINE (Systemic): Potassium-Sparing Diuretics may enhance the hyperkalemic effect of CycloSPORINE (Systemic).Risk X: Avoid combinationCYP2C8 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Spironolactone may increase the serum concentration of CYP2C8 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors).Risk C: Monitor therapyCYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Spironolactone may increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors).Risk C: Monitor therapyDesmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin.Risk C: Monitor therapyDexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapyDiacerein: May enhance the therapeutic effect of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased. Risk C: Monitor therapyDiazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyDigoxin: Spironolactone may increase the serum concentration of Digoxin. Spironolactone (and/or its metabolites) may also interfere with the assays used to determine Digoxin concentrations, falsely increasing or decreasing Digoxin concentrations.Risk C: Monitor therapyDrospirenone-Containing Products: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapyDULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine.Risk C: Monitor therapyEplerenone: Spironolactone may enhance the hyperkalemic effect of Eplerenone.Risk X: Avoid combinationFinerenone: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of Finerenone.Risk C: Monitor therapyFludrocortisone: May diminish the therapeutic effect of Mineralocorticoid (Aldosterone) Receptor Antagonists. Mineralocorticoid (Aldosterone) Receptor Antagonists may diminish the therapeutic effect of Fludrocortisone. Risk C: Monitor therapyFlunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapyHeparin: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: Monitor serum potassium concentrations closely. The spironolactone Canadian product monograph lists its combination with heparin or low molecular weight heparins as contraindicated. Risk C: Monitor therapyHeparins (Low Molecular Weight): May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: Monitor serum potassium concentrations closely. The spironolactone Canadian product monograph lists its combination with heparin or low molecular weight heparins as contraindicated. Risk C: Monitor therapyHerbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapyHerbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyHypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents.Risk C: Monitor therapyLevodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products.Risk C: Monitor therapyLoop Diuretics: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapyLormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyMethylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapyMitotane: Spironolactone may decrease the serum concentration of Mitotane.Risk C: Monitor therapyMolsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyNaftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyNicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyNicorandil: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapyNicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyNitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside.Risk C: Monitor therapyNonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapyObinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modificationOpioid Agonists: May enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Risk C: Monitor therapyPentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyPholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine.Risk C: Monitor therapyPhosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyPotassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: Avoid coadministration of a potassium-sparing diuretic and a potassium salt. This combination should only be used in cases of significant hypokalemia, and only if serum potassium can be closely monitored. Risk D: Consider therapy modificationProstacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyQuinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapyQuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine.Risk C: Monitor therapySodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced.Risk C: Monitor therapyTacrolimus (Systemic): Potassium-Sparing Diuretics may enhance the hyperkalemic effect of Tacrolimus (Systemic).Risk C: Monitor therapyTolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapyTriamterene: May enhance the hyperkalemic effect of Spironolactone. Risk X: Avoid combinationTrimethoprim: May enhance the hyperkalemic effect of Spironolactone. Risk C: Monitor therapyFood InteractionsFood increases the bioavailability of unmetabolized spironolactone by ~90% to 95%.Reproductive ConsiderationsSpironolactone is associated with dose-dependent menstrual irregularities (AAD [Zaenglein 2016]; ES [Funder 2016]; ES [Martin 2018]; Kallistratos 2018). Some guidelines recommend use of combination oral contraception in premenopausal patients to regulate menses and prevent pregnancy (AAD [Zaenglein 2016], ES [Martin 2018]). Decreasing the dose or switching to an alternative mineralocorticoid receptor antagonist may be appropriate for some indications (AHA [Carey 2018]; ES [Funder 2016]; Kallistratos 2018).Spironolactone is associated with dose-dependent erectile dysfunction (AAD [Zaenglein 2016]; ES [Funder 2016]; ES [Martin 2018]; Kallistratos 2018). Decreasing the dose or switching to an alternative mineralocorticoid receptor antagonist may be appropriate for some indications (AHA [Carey 2018]; ES [Funder 2016]; Kallistratos 2018). The antiandrogen blocking activity of spironolactone results in decreased spontaneous erections, sperm production, and testicular volume in transgender patients undergoing feminizing therapy (ES [Hembree 2017]).Patients taking spironolactone for primary aldosteronism (PA) who are planning to become pregnant should be switched to other agents prior to conception when possible (Forestiero 2022). Patients who require use of spironolactone for the treatment of PA should use the lowest effective dose prior to a planned pregnancy, then stop treatment once their pregnancy is confirmed (Riester 2015).Patients with heart failure who are planning to become pregnant should discontinue mineralocorticoid receptor antagonists prior to conception (AHA/ACC/HFSA [Heidenreich 2022]).Pregnancy ConsiderationsSpironolactone crosses the placenta (ESC [Regitz-Zagrosek 2018]).Based on the mechanism of action and data from animal reproduction studies, in utero exposure to spironolactone during the period of embryogenesis may cause feminization of a male fetus (limited human data; Liszewski 2019). High doses late in pregnancy may be associated with intrauterine growth restriction (Riester 2015).Chronic maternal hypertension is associated with adverse events in the fetus/infant. The risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death may be increased with chronic hypertension in pregnancy. Actual risks may be related to duration and severity of maternal hypertension. The use of mineralocorticoid receptor antagonists for the treatment of hypertension in pregnancy is generally not recommended (ACOG 203 2019).The treatment of edema associated with chronic heart failure during pregnancy is similar to that of nonpregnant patients. However, the use of mineralocorticoid receptor antagonists is not recommended. Patients diagnosed after delivery can be treated according to heart failure guidelines (AHA/ACC/HFSA [Heidenreich 2022]; ESC [Bauersachs 2016]; ESC [Regitz-Zagrosek 2018]).Data specific to the treatment of primary aldosteronism (PA) in pregnancy are limited. Patients with PA should stop spironolactone before conception or during the first trimester once the pregnancy is confirmed (Riester 2015). If spironolactone is stopped and PA is not controlled, agents other than spironolactone are recommended for the adjunctive treatment of PA during pregnancy (Forestiero 2022; Sanga 2022).Case reports describe the use of potassium-sparing diuretics such as spironolactone for the adjunctive treatment of Gitleman syndrome during pregnancy (Calò 2012; Moustakakis 2012; Shahzad 2019).Breastfeeding ConsiderationsThe active metabolite of spironolactone (canrenone) is present in breast milk.Data are available from a case report following maternal use of spironolactone 25 mg twice daily throughout pregnancy, then 4 times daily after delivery. Milk and maternal serum samples were obtained 17 days after birth. Two hours after the maternal dose, canrenone concentrations were ~144 ng/mL (serum) and ~104 ng/mL (milk). When measured 14.5 hours after the dose, canrenone concentrations were ~92 ng/mL (serum) and ~47 ng/mL (milk). The authors calculated the estimated maximum amount of canrenone to the breastfeeding infant to be ~0.2% of the maternal dose of spironolactone (Phelps 1977).Spironolactone is considered compatible with breastfeeding (WHO 2002). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.Dietary ConsiderationsAdministration with food increases the bioavailability of spironolactone. Excessive potassium intake (eg, salt substitutes, low-salt foods, bananas, nuts) should be avoided.Monitoring ParametersBlood pressure, serum electrolytes (potassium [within 1 week of initiation or dose titration and regularly thereafter], sodium), uric acid, glucose, renal function, volume statusHeart failure: Serum potassium and renal function should be checked in 3 days after initiation, at 1 week after initiation, at least monthly for the first 3 months of therapy, and every 3 months thereafter. If adding or increasing the dose of concomitant ACE inhibitors or ARBs, a new cycle of monitoring should be done. If serum potassium increases to >5.5 mEq/L or renal function worsens, hold doses until potassium is <5 mEq/L and consider restarting with a reduced dose after confirming resolution of hyperkalemia/renal insufficiency for at least 72 hours (ACCF/AHA [Yancy 2013]).Transgender hormone therapy: Serum testosterone levels (goal: <50 ng/dL) every 3 months during the first year and then annually or biannually; serum electrolytes every 3 months for the first year then annually; routine cancer and laboratory screening as in non-transgender individuals for all tissues present (ES [Hembree 2017]).Mechanism of ActionCompetes with aldosterone for receptor sites in the distal renal tubules, increasing sodium chloride and water excretion while conserving potassium and hydrogen ions; may block the effect of aldosterone on arteriolar smooth muscle as wellPharmaco*kineticsNote: Suspension results in 15% to 37% higher serum concentration compared to the tablet; doses of suspension >100 mg may result in higher spironolactone concentrations than expected.Duration: Tablet: 2 to 3 daysBioavailability: High-fat/-calorie meal increased the bioavailability of spironolactone ~90%.Protein binding: >90%Metabolism: Rapid and extensive; hepatic to multiple metabolites, including active metabolites canrenone, 7-alpha-spirolactone, and 6-beta-hydroxy-7-alphaHalf-life elimination:Tablet: Spironolactone: 1.4 hours; Canrenone: 16.5 hours (terminal); 7-alpha-spirolactone: 13.8 hours (terminal)Suspension: Spironolactone: 1 to 2 hours; Canrenone, 7-alpha-spirolactone, and 6-beta-hydroxy-7-alpha: 10 to 35 hours.Time to peak, serum:Tablet: 2.6 to 4.3 hours (primarily as active metabolites)Suspension: Spironolactone: 0.5 to 1.5 hours; Canrenone: 2.5 to 5 hoursExcretion: Urine (primarily as metabolites) and bile (secondary)Pharmaco*kinetics: Additional ConsiderationsHepatic function impairment: Terminal half-life is increased in patients with cirrhotic ascites.Pricing: USSuspension (CaroSpir Oral)25 mg/5 mL (per mL): $4.23Tablets (Aldactone Oral)25 mg (per each): $3.1950 mg (per each): $5.60100 mg (per each): $9.38Tablets (Spironolactone Oral)25 mg (per each): $0.19 - $0.4650 mg (per each): $0.81 - $0.88100 mg (per each): $1.42 - $1.43Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalAldactin (TW);Aldacton (TR);Aldactone (AE, AT, AU, BB, BD, BE, BF, BH, BJ, BR, CH, CI, CO, CY, CZ, DE, EC, EE, ES, ET, FI, FR, GB, GH, GM, GN, GR, HK, HR, HU, ID, IE, IL, IN, IQ, IR, IS, IT, JO, KE, KR, KW, LB, LK, LR, LU, LY, MA, ML, MR, MT, MU, MW, MX, NE, NG, NO, OM, PE, PH, PK, PT, QA, RU, SA, SC, SD, SE, SG, SI, SK, SL, SN, SY, TH, TN, TZ, UG, VE, YE, ZA, ZM, ZW);Aldactone A (AR, BM, BS, BZ, CR, DO, EC, GT, GY, HN, JM, NI, PA, SR, SV, TT, UY);Aldoxol (PY);Alizar (CL);Alspiron (RO);Altone (TH);Antagerone (EG);Belactone (LK);Diulactone (PH, VN);Drimox A (AR);Epilactone (EG);Expal (AR);Finospir (PL);Huma-Spiroton (HU);Indurit (PY);Ismian (PL);Lactone (PH);Laxtone (TW);Noractone (AE, JO);Osiren (AR, AT);Osyrol (JP);Pondactone (TH);Skyton (TW);Spectone (EG);Spilac (LK);Spinolac (VN);Spiractin (AU, NZ, ZA);Spiralang (IT);Spiretic (BD);Spirix (DK, FI, NO);Spiroctan (FR, LU);Spirofar (PH);Spirola (ID);Spirolacton (ID);Spirolon (BF, BJ, CI, EC, ET, GH, GM, GN, KE, LR, MA, ML, MR, MT, MU, MW, MY, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW);Spiron (DK, HU, TW);Spirone (PE);Spironolacton-ratiopharm (LU);Spironolactone-Eurogenerics (LU);Spironolactone-Searle (LU);Spirotone (NZ, TW);Unilactone (AE, BH, CY, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE);Uractone (LU);Uractonum (SG, TR);Verospiron (BD, BG, CZ, EE, HU, LT, SK, UA);Vivitar (CR, DO, GT, HN, MX, NI, PA, SV)For country code abbreviations (show table)<800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 40-NF 35). Rockville, MD: United States Pharmacopeia Convention; 2017:83-102.2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674-694. doi:10.1111/jgs.15767 [PubMed 30693946]Agarwal R, Rossignol P, Romero A, et al. Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2019;394(10208):1540-1550. doi:10.1016/S0140-6736(19)32135-X [PubMed 31533906]Albersheim SG, Solimano AJ, Sharma AK, et al. Randomized, double-blind, controlled trial of long-term diuretic therapy for bronchopulmonary dysplasia. J Pediatr. 1989;115(4):615-620. [PubMed 2677293]Aldactone (spironolactone) [prescribing information]. New York, NY: Pfizer Inc; February 2021.Aldactone (spironolactone) [product monograph]. Kirkland, Quebec, Canada: Pfizer Canada Inc; July 2015.American College of Obstetricians and Gynecologists (ACOG). ACOG practice bulletin no. 203: chronic hypertension in pregnancy. Obstet Gynecol. 2019;133(1):e26-e50. [PubMed 30575676]Amsterdam EA, Wenger NK, Brindis RG, et al; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; American Association for Clinical Chemistry. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [published correction appears in J Am Coll Cardiol. 2014;64(24):2713-2714]. J Am Coll Cardiol. 2014;64(24):e139-e228. doi:10.1016/j.jacc.2014.09.017 [PubMed 25260718]Aronow WS, Fleg JL, Pepine CJ, et al. ACC/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus documents developed in collaboration with the American Academy of Neurology, American Geriatrics Society, American Society for Preventive Cardiology, American Society of Hypertension, American Society of Nephrology, Association of Black Cardiologists, and European Society of Hypertension. J Am Coll Cardiol. 2011;57(20):2037-2114. [PubMed 21524875]ASHP. Standardize 4 Safety Initiative Compounded Oral Liquid Version 1.01. July 2017. https://www.ashp.org/-/media/assets/pharmacy-practice/s4s/docs/s4s-ashp-oral-compound-liquids.ashx?la=en&hash=4C2E4F370B665C028981B61F6210335AD5D0D1D6.Bakris GL, Pitt B, Weir MR, et al.; AMETHYST-DN Investigators. Effect of patiromer on serum potassium level in patients with hyperkalemia and diabetic kidney disease: the AMETHYST-DN randomized clinical trial. JAMA. 2015;314(2):151-161. doi:10.1001/jama.2015.7446 [PubMed 26172895]Barbieri RL, Chang J. Management of hirsutism in premenopausal women. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 29, 2021.Barrionuevo P, Nabhan M, Altavar O, et al. Treatment options for hirsutism: a systematic review and network meta-analysis. J Clin Endocrinol Metab. 2018;103(4):1258-1264. doi:10.1210/jc.2017-02052 [PubMed 29522176]Based on expert opinion.Bauersachs J, Arrigo M, Hilfiker-Kleiner D, et al. Current management of patients with severe acute peripartum cardiomyopathy: practical guidance from the Heart Failure Association of the European Society of Cardiology Study Group on peripartum cardiomyopathy. Eur J Heart Fail. 2016;18(9):1096-1105. [PubMed 27338866]Bazoukis G, Thom*opoulos C, Tsioufis C. Effect of mineralocorticoid antagonists on blood pressure lowering: overview and meta-analysis of randomized controlled trials in hypertension. J Hypertens. 2018;36(5):987-994. doi:10.1097/HJH.0000000000001671 [PubMed 29356711]Ben Salem C, Slim R, Fathallah N, Hmouda H. Drug-induced hyperuricaemia and gout. Rheumatology (Oxford). 2017;56(5):679-688. doi:10.1093/rheumatology/kew293 [PubMed 27498351]Borlaug BA, Colucci WS. Treatment and prognosis of heart failure with preserved ejection fraction. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 10, 2022.Brook RD, Townsend RR. Treatment of resistant hypertension. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 8, 2020.Calò LA, Caielli P. Gitelman's syndrome and pregnancy: new potential pathophysiological influencing factors, therapeutic approach and materno-fetal outcome. J Matern Fetal Neonatal Med. 2012;25(8):1511-1513. doi:10.3109/14767058.2011.629254 [PubMed 21999963]Carey RM, Calhoun DA, Bakris GL, et al; American Heart Association Professional/Public Education and Publications Committee of the Council on Hypertension; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Genomic and Precision Medicine; Council on Peripheral Vascular Disease; Council on Quality of Care and Outcomes Research; and Stroke Council. Resistant hypertension: detection, evaluation, and management: a scientific statement from the American Heart Association. Hypertension. 2018;72(5):e53-e90. doi:10.1161/HYP.0000000000000084 [PubMed 30354828]Carospir (spironolactone) [prescribing information]. Farmville, NC: CMP Pharma Inc; July 2021.Charytan DM, Himmelfarb J, Ikizler TA, et al.; Hemodialysis Novel Therapies Consortium. Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): a randomized, placebo-controlled, multiple dosage trial. Kidney Int. 2019;95(4):973-982. doi:10.1016/j.kint.2018.08.034 [PubMed 30473139]Colucci WS. Secondary pharmacologic therapy in heart failure with reduced ejection fraction (HFrEF) in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 2, 2021.Deutsch MB. Guidelines for the primary and gender-affirming care of transgender and nonbinary people. Center of Excellence for Transgender Health. http://transhealth.ucsf.edu/trans?page=guidelines-home. Published June 17, 2016. Accessed January 14, 2019.De Vecchis R, Cantatrione C, Mazzei D, Barone A, Maurea N. The Impact Exerted on Clinical Outcomes of Patients With Chronic Heart Failure by Aldosterone Receptor Antagonists: A Meta-Analysis of Randomized Controlled Trials. J Clin Med Res. 2017;9(2):130-142. doi:10.14740/jocmr2851w [PubMed 28090229]Eichenwald EC, ed. Cloherty and Stark's Manual of Neonatal Care. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2017.Engelhardt B, Blalock WA, DonLevy S, Rush M, Hazinski TA. Effect of spironolactone-hydrochlorothiazide on lung function in infants with chronic bronchopulmonary dysplasia. J Pediatr. 1989;114(4 Pt 1):619-624. [PubMed 2926575]Fanaroff AA, Fanaroff JM, eds. Klaus & Fanaroff's Care of the High-Risk Neonate. 6th ed. Philadelphia, PA: Elsevier Saunders; 2013.Feinfeld DA, Carvounis CP. Fatal hyperkalemia and hyperchloremic acidosis. Association with spironolactone in the absence of renal impairment. JAMA. 1978;240(14):1516. doi:10.1001/jama.240.14.1516 [PubMed 682358]Forestiero V, Sconfienza E, Mulatero P, Monticone S. Primary aldosteronism in pregnancy. Rev Endocr Metab Disord. Published online May 10, 2022. doi:10.1007/s11154-022-09729-6 [PubMed 35536535]Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi:10.1210/jc.2015-4061 [PubMed 26934393]Gabow PA, Moore S, Schrier RW. Spironolactone-induced hyperchloremic acidosis in cirrhosis. Ann Intern Med. 1979;90(3):338-340. doi:10.7326/0003-4819-90-3-338 [PubMed 426401]Georgianos PI, Agarwal R. Pharmacotherapy of hypertension in chronic dialysis patients. Clin J Am Soc Nephrol. 2016;11(11):2062-2075. doi:10.2215/CJN.00870116 [PubMed 27797886]Giefer MJ, Murray KF, Colletti RB. Pathophysiology, diagnosis, and management of pediatric ascites. J Pediatr Gastroenterol Nutr. 2011;52(5):503-513. [PubMed 21464748]Go AS, Bauman M, King SM, et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention [published online November 15, 2013]. Hypertension. [PubMed 24243703]Goodfellow A, Alaghband-Zadeh J, Carter G, et al. Oral spironolactone improves acne vulgaris and reduces sebum excretion. Br J Dermatol. 1984;111(2):209-214. doi:10.1111/j.1365-2133.1984.tb04045.x [PubMed 6235834]Graber E. Acne vulgaris: Management of moderate to severe acne in adolescents and adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 3, 2022.Gueiros APS, Gueiros JEB, Nóbrega KT, et al. Effect of spironolactone on the progression of coronary calcification in peritoneal dialysis patients: a pilot study. J Bras Nefrol. 2019;41(3):345-355. doi:10.1590/2175-8239-jbn-2019-0009 [PubMed 31419271]Hammer F, Malzahn U, Donhauser J, et al.; MiREnDa Study Group. A randomized controlled trial of the effect of spironolactone on left ventricular mass in hemodialysis patients. Kidney Int. 2019;95(4):983-991. doi:10.1016/j.kint.2018.11.025 [PubMed 30712923]Haynes BA, Mookadam F. Male gynecomastia. Mayo Clin Proc. 2009;84(8):672. doi:10.1016/S0025-6196(11)60515-6 [PubMed 19648382]Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18):e895-e1032. doi:10.1161/CIR.0000000000001063 [PubMed 35363499]Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an Endocrine Society clinical practice guideline. Endocr Pract. 2017;23(12):1437. doi:10.4158/1934-2403-23.12.1437 [PubMed 29320642]Hoffman DJ, Gerdes JS, Abbasi S. Pulmonary function and electrolyte balance following spironolactone treatment in preterm infants with chronic lung disease: a double-blind, placebo-controlled, randomized trial. J Perinatol. 2000;20(1):41-45. [PubMed 10693099]Huang C, Noirot LA, Reichley RM, Bouselli DA, Dunagan WC, Bailey TC. Automatic detection of spironolactone - related adverse drug events. AMIA Annu Symp Proc. 2005;2005:989. [PubMed 16779276]Ito Y, Mizuno M, Suzuki Y, et al.; Nagoya Spiro Study Group. Long-term effects of spironolactone in peritoneal dialysis patients. J Am Soc Nephrol. 2014;25(5):1094-1102. doi:10.1681/ASN.2013030273 [PubMed 24335969]James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520. [PubMed 24352797]Jeunemaitre X, Chatellier G, Kreft-Jais C, et al. Efficacy and tolerance of spironolactone in essential hypertension. Am J Cardiol. 1987;60(10):820-825. doi:10.1016/0002-9149(87)91030-7 [PubMed 3661395]Juurlink DN, Mamdani MM, Lee DS, et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med. 2004;351(6):543-551. doi:10.1056/NEJMoa040135 [PubMed 15295047]Kallistratos MS, Pittaras A, Theodoulidis I, Grassos C, Poulimenos LE, Manolis AJ. Adverse effects of mineralocorticoid receptor antagonist administration. Curr Pharm Des. 2018;24(46):5537-5541. doi:10.2174/1381612825666190222144359 [PubMed 30799782]Kliegman RM, Stanton BMD, St. Geme J, Schor NF, eds. Nelson Textbook of Pediatrics. 20th ed. Philadelphia, PA: Saunders Elsevier; 2016.Levitt JI. Spironolactone therapy and amenorrhea. JAMA. 1970;211(12):2014-2015. [PubMed 5467162]Liszewski W, Boull C. Lack of evidence for feminization of males exposed to spironolactone in utero: a systematic review. J Am Acad Dermatol. 2019;80(4):1147-1148. [PubMed 30352280]Mackenzie IS, Morant SV, Wei L, Thompson AM, MacDonald TM. Spironolactone use and risk of incident cancers: a retrospective, matched cohort study. Br J Clin Pharmacol. 2017;83(3):653-663. doi:10.1111/bcp.13152 [PubMed 27735065]Maddox TM, Januzzi JL Jr, Allen LA, et al. 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021;77(6):772-810. doi:10.1016/j.jacc.2020.11.022 [PubMed 33446410]Mann JFE. Choice of drug therapy in primary (essential) hypertension. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 23, 2021.Martin KA, Anderson RR, Chang RJ, et al. Evaluation and treatment of hirsutism in premenopausal women: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(4):1233-1257. doi:10.1210/jc.2018-00241 [PubMed 29522147]Moustakakis MN, Bockorny M. Gitelman syndrome and pregnancy. Clin Kidney J. 2012;5(6):552-555. doi:10.1093/ckj/sfs126 [PubMed 26064481]Muhlemann MF, Carter GD, Cream JJ, Wise P. Oral spironolactone: an effective treatment for acne vulgaris in women. Br J Dermatol. 1986;115(2):227-232. doi:10.1111/j.1365-2133.1986.tb05722.x [PubMed 2943311]Mulatero P, Rabbia F, Milan A, Paglieri C, Morello F, Chiandussi L, Veglio F. Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism. Hypertension. 2002;40(6):897-902. [PubMed 12468576]National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Pediatrics. 2004;114(2)(suppl 4th Report):555-576. [PubMed 15286277]Nuttall FQ, Warrier RS, Gannon MC. Gynecomastia and drugs: a critical evaluation of the literature. Eur J Clin Pharmacol. 2015;71(5):569-578. doi:10.1007/s00228-015-1835-x [PubMed 25827472]O'Gara PT, Kushner FG, Ascheim DD, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(4):e362-e425. [PubMed 23247304]Oxlund CS, Henriksen JE, Tarnow L, Schousboe K, Gram J, Jacobsen IA. Low dose spironolactone reduces blood pressure in patients with resistant hypertension and type 2 diabetes mellitus: a double blind randomized clinical trial. J Hypertens. 2013;31(10):2094-2102. doi:10.1097/HJH.0b013e3283638b1a [PubMed 24107738]Park, MK. Park's Pediatric Cardiology for Practitioners. 6th ed. Philadelphia, PA: Elsevier Health Sciences; 2014.Phelps DL, Karim A. Spironolactone: relationship between concentrations of dethioacetylated metabolite in human serum and milk. J Pharm Sci. 1977;66(8):1203. [PubMed 894512]Pitt B, Pfeffer MA, Assmann SF, et al; TOPCAT Investigators. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370(15):1383-1392. doi:10.1056/NEJMoa1313731 [PubMed 24716680]Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction [published correction appears in N Engl J Med. 2003 May 29;348(22):2271]. N Engl J Med. 2003;348(14):1309-1321. doi:10.1056/NEJMoa030207 [PubMed 12668699]Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341(10):709-717. doi:10.1056/NEJM199909023411001 [PubMed 10471456]Prior JC, Vigna YM, Watson D. Spironolactone with physiological female steroids for presurgical therapy of male-to-female transsexualism. Arch Sex Behav. 1989;18(1):49-57. doi:10.1007/bf01579291 [PubMed 2540730]Prisant LM, Chin E. Gynecomastia and hypertension. J Clin Hypertens (Greenwich). 2005;7(4):245-248. doi:10.1111/j.1524-6175.2005.04105.x [PubMed 15860966]Refer to manufacturer's labeling.Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J. 2018;39(34):3165-3241. [PubMed 30165544]Riester A, Reincke M. Progress in primary aldosteronism: mineralocorticoid receptor antagonists and management of primary aldosteronism in pregnancy. Eur J Endocrinol. 2015;172(1):R23-R30. [PubMed 25163723]Rose LI, Underwood RH, Newmark SR, Kisch ES, Williams GH. Pathophysiology of spironolactone-induced gynecomastia. Ann Intern Med. 1977;87(4):398-403. doi:10.7326/0003-4819-87-4-398 [PubMed 907238]Rozner RN, Freites-Martinez A, Shapiro J, Geer EB, Goldfarb S, Lacouture ME. Safety of 5α-reductase inhibitors and spironolactone in breast cancer patients receiving endocrine therapies. Breast Cancer Res Treat. 2019;174(1):15-26. doi:10.1007/s10549-018-4996-3 [PubMed 30467659]Runyon BA. Ascites in adults with cirrhosis: Initial therapy. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 7, 2020.Runyon BA; AASLD. Introduction to the revised American Association for the Study of Liver Diseases practice guideline management of adult patients with ascites due to cirrhosis 2012. Hepatology. 2013;57(4):1651-1653. doi:10.1002/hep.26359 [PubMed 23463403]Sabatier P, Amar J, Montastruc F, et al. Breast cancer and spironolactone: an observational postmarketing study. Eur J Clin Pharmacol. 2019;75(11):1593-1598. doi:10.1007/s00228-019-02740-y [PubMed 31418056]Sabri M, Saps M, Peters JM. Pathophysiology and management of pediatric ascites. Curr Gastroenterol Rep. 2003;5(3):240-246. [PubMed 12734047]Sanga V, Rossitto G, Seccia TM, Rossi GP. Management and outcomes of primary aldosteronism in pregnancy: a systematic review. Hypertension. 2022;79(9):1912-1921. doi:10.1161/HYPERTENSIONAHA.121.18858 [PubMed 35686552]Shah KB, Rao K, Sawyer R, Gottlieb SS. The adequacy of laboratory monitoring in patients treated with spironolactone for congestive heart failure. J Am Coll Cardiol. 2005;46(5):845-849. doi:10.1016/j.jacc.2005.06.010 [PubMed 16139135]Shahzad MA, Mukhtar M, Ahmed A, Ullah W, Saeed R, Hamid M. Gitelman syndrome: a rare cause of seizure disorder and a systematic review. Case Rep Med. 2019;2019:4204907. doi:10.1155/2019/4204907 [PubMed 30867665]Shaw JC. Low-dose adjunctive spironolactone in the treatment of acne in women: a retrospective analysis of 85 consecutively treated patients. J Am Acad Dermatol. 2000;43(3):498-502. doi:10.1067/mjd.2000.105557 [PubMed 10954662]Slaughter JL, Stenger MR, Reagan PB. Variation in the use of diuretic therapy for infants with bronchopulmonary dysplasia. Pediatrics. 2013;131(4):716-723. [PubMed 23478874]Smith SC Jr, Benjamin EJ, Bonow RO, et al. AHA/ACC Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2011 Update: A Guideline From the American Heart Association and American College of Cardiology Foundation. Circulation. 2011;124(22):2458-2473. [PubMed 22052934]Spinowitz BS, Fishbane S, Pergola PE, et al.; ZS-005 Study Investigators. Sodium zirconium cyclosilicate among Individuals with hyperkalemia: a 12-month phase 3 study. Clin J Am Soc Nephrol. 2019;14(6):798-809. doi:10.2215/CJN.12651018 [PubMed 31110051]Stewart A, Brion LP, Ambrosio-Perez I. Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease. Cochrane Database Syst Rev. 2011;(9):CD001817. [PubMed 21901679]Tamirisa KP, Aaronson KD, Koelling TM. Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure. Am Heart J. 2004;148(6):971-978. doi:10.1016/j.ahj.2004.10.005 [PubMed 15632880]Thiede RM, Rastogi S, Nardone B, et al. Hyperkalemia in women with acne exposed to oral spironolactone: a retrospective study from the RADAR (Research on Adverse Drug Events and Reports) program. Int J Womens Dermatol. 2019;5(3):155-157. doi:10.1016/j.ijwd.2019.04.024 [PubMed 31360748]US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. http://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf. Updated September 2016. Accessed October 5, 2016.Vachharajani AJ, Shah JK, Paes BA. Ovarian cyst in a premature infant treated with spironolactone. Am J Perinatol. 2001;18(6):353-356. [PubMed 11607853]van der Vorst MM, Kist JE, van der Heijden AJ, Burggraaf J. Diuretics in pediatrics: current knowledge and future prospects. Paediatr Drugs. 2006;8(4):245-264. [PubMed 16898855]Vardeny O, Claggett B, Anand I, et al. Incidence, predictors, and outcomes related to hypo- and hyperkalemia in patients with severe heart failure treated with a mineralocorticoid receptor antagonist. Circ Heart Fail. 2014;7(4):573-579. doi:10.1161/CIRCHEARTFAILURE.114.001104 [PubMed 24812304]Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014;16(1):14-26. doi:10.1111/jch.12237 [PubMed 24341872]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in Hypertension. 2018;71(6):e140-e144]. Hypertension. 2018;71(6):e13-e115. doi:10.1161/HYP.0000000000000065 [PubMed 29133356]Whitling AM, Pérgola PE, Sang JL, Talbert RL. Spironolactone-induced agranulocytosis. Ann Pharmacother. 1997;31(5):582-585. doi:10.1177/106002809703100511 [PubMed 9161653]Williams B, MacDonald TM, Morant S, et al; British Hypertension Society's PATHWAY Studies Group. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015;386(10008):2059-2068. doi:10.1016/S0140-6736(15)00257-3 [PubMed 26414968]World Health Organization (WHO). Breastfeeding and maternal medication, recommendations for drugs in the eleventh WHO model list of essential drugs. 2002. https://apps.who.int/iris/handle/10665/62435Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136(6):e137-e161. doi:10.1161/CIR.0000000000000509 [PubMed 28455343]Yancy CW, Jessup M, Bozkurt B, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;128(16):e240-e327. doi:10.1161/CIR.0b013e31829e8776 [PubMed 23741058]Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Card Fail. 2017;23(8):628-651. doi:10.1016/j.cardfail.2017.04.014 [PubMed 28461259]Yemisci A, Gorgulu A, Piskin S. Effects and side-effects of spironolactone therapy in women with acne. J Eur Acad Dermatol Venereol. 2005;19(2):163-166. doi:10.1111/j.1468-3083.2005.01072.x [PubMed 15752283]Young WF Jr. Treatment of primary aldosteronism. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 10, 2020.Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945-973.e33. doi:10.1016/j.jaad.2015.12.037 [PubMed 26897386]Topic 9943 Version 470.0

CloseTranexamic acid: Pediatric drug informationTranexamic acid: Pediatric drug information(For additional information see "Tranexamic acid: Drug information" and see "Tranexamic acid: Patient drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USCyklokapron;LystedaBrand Names: CanadaCyklokapron;Erfa-Tranexamic;GD-Tranexamic Acid;MAR-Tranexamic AcidTherapeutic CategoryAntifibrinolytic Agent;Antihemophilic Agent;Hemostatic AgentDosing: NeonatalPrevention of bleeding associated with extracorporeal membrane oxygenation during surgery for congenital diaphragmatic hernia repair: Limited data available: Term neonates: IV: Loading dose: 4 mg/kg as a single dose 30 to 60 minutes before repair, followed by a continuous IV infusion of 1 mg/kg/hour for 24 hours, was reported to reduce blood loss and hemorrhagic complications (Ref).Prevention of perioperative bleeding: Limited data available; reported dosing regimens variable and ideal dose-response not established:General dosing (non-cardiac): IV: Loading dose: 10 to 30 mg/kg followed by a continuous IV infusion at 5 to 10 mg/kg/hour; dosing based on a pharmaco*kinetic model to achieve a target serum concentration of 20 mcg/mL and 70 mcg/mL, respectively (Ref).Cardiac surgery with cardiopulmonary bypass: Low dose: IV: Loading dose: 10 mg/kg followed by a continuous IV infusion at 5 mg/kg/hour; dosing based on a pharmaco*kinetic model to achieve a target serum concentration of 20 mcg/mL; tranexamic acid must also be added to cardiopulmonary bypass solution at a concentration of 20 mcg/mL (Ref). A pharmaco*kinetic analysis (n=43; mean age: 123 days [range: 6 to 348 days]; mean weight: 4.95 kg [range: 2.3 to 9.5 kg]) targeting a serum concentration of 20 mcg/mL proposed the following regimen: Loading dose: 10 mg/kg, followed by a continuous IV infusion at 10 mg/kg/hour until initiation of cardiopulmonary bypass, then IV priming bolus: 4 mg/kg into the bypass prime volume, followed by a continuous IV infusion at 4 mg/kg/hour (Ref).Intermediate dose: IV: Loading dose: 30 mg/kg followed by a continuous IV infusion at 10 mg/kg/hour; dosing based on a pharmaco*kinetic model to achieve a target serum concentration of 70 mcg/mL; tranexamic acid must also be added to cardiopulmonary bypass solution at a concentration of 70 mcg/mL (Ref).High dose: IV: Loading dose: 100 mg/kg over 15 minutes, then a priming dose: 100 mg/kg into the by-pass circuit followed by a continuous IV infusion at 10 mg/kg/hour (Ref).Dosing adjustment in renal impairment: Prophylaxis or treatment of mild to major bleeding secondary to surgery: There are no specific neonatal dosage adjustments provided in the manufacturer's labeling; however, due to risk of accumulation with kidney impairment, dosage adjustments are recommended (Ref).Dosing: PediatricDiffuse alveolar hemorrhage, treatmentDiffuse alveolar hemorrhage (intractable), treatment: Very limited data available (Ref), ideal dose-response not established:Children ≤25 kg: Inhaled: 250 mg every 6 hours for 3 to 4 doses (18 to 24 hours); if response occurs, continue treatment for another 2 to 3 doses after bleeding completely stops; if no or minimal response or bleeding worsens, add inhaled recombinant factor VIIa; maximum duration of inhaled therapy: 3 days.Children >25 kg and Adolescents: Inhaled: 500 mg inhaled every 6 hours for 3 to 4 doses (18 to 24 hours); if response occurs, continue treatment for another 2 to 3 doses after bleeding completely stops; if no or minimal response or bleeding worsens, add inhaled recombinant factor VIIa; maximum duration of inhaled therapy: 3 days.Dosing based on a prospective pilot study of 18 children (median age: 24 months [interquartile range: 11.3 to 58.5 months]) with intractable diffuse alveolar hemorrhage (DAH) who received inhaled tranexamic acid; DAH responded to inhaled tranexamic treatment alone in 10 children (56%); the 8 nonresponders had inhaled recombinant factor VIIa added; 75% (n=6) of these patients had complete cessation of DAH; none of the patients who responded to treatment had recurrence or complications reported (Ref). Two retrospective studies have reported doses of 250 to 500 mg every 6 to 12 hours until resolution of bleeding for pulmonary hemorrhages (Ref).Hereditary angioedema, prophylaxisHereditary angioedema (HAE), prophylaxis: Limited data available:Long-term prophylaxis: Note: Not the preferred treatment option; reserve use for when C1-inhibitor concentrate is unavailable (Ref).Children and Adolescents: Oral: 20 to 50 mg/kg/day in 2 to 3 divided doses; doses up to 75 mg/kg/day have been reported; maximum daily dose range: 3,000 to 6,000 mg/day (Ref); may consider alternate-day regimen or twice-weekly regimen when frequency of attacks reduces (Ref).Short-term prophylaxis (eg, prior to surgical or diagnostic interventions in head/neck region): Note: Not the preferred treatment option; some experts do not recommend use for short-term prophylaxis (Ref).Weight directed: Children and Adolescents: Oral: 20 to 50 mg/kg/day in 2 to 3 divided doses; maximum daily dose range: 3,000 to 6,000 mg/day; initiate therapy at least 5 days before and continue for 2 days postprocedure (Ref).Fixed dosing: Children and Adolescents: Patients with an adequate weight (eg, ≥50 kg): Oral: 500 mg 4 times daily (Ref); therapy usually initiated 2 to 5 days before dental work and continue for 2 days after the procedure (Ref).Menstrual bleeding, heavyMenstrual bleeding, heavy: Postmenarche female: Tablet (Lysteda): Oral: 1,300 mg 3 times daily for up to 5 days during monthly menstruation; maximum daily dose: 3,900 mg/day.Prevention of bleeding associated with tooth extraction in hemophilic patientsPrevention of bleeding associated with tooth extraction in hemophilic patients: Note: Use in combination with replacement therapy.Infants, Children, and Adolescents: IV: 10 mg/kg immediately before surgery, then 10 mg/kg/dose 3 to 4 times daily for 2 to 8 days.Prevention of perioperative bleedingPrevention of perioperative bleeding: Limited data available; reported regimens variable and ideal dose-response not established:General dosing (non-cardiac): Infants, Children, and Adolescents: IV: Loading dose: 10 to 30 mg/kg followed by a continuous IV infusion at 5 to 10 mg/kg/hour; dosing based on a pharmaco*kinetic model to achieve a target serum concentration of 20 mcg/mL and 70 mcg/mL, respectively (Ref).Cardiac surgery with cardiopulmonary bypass: Infants, Children, and Adolescents:Low dose: IV: Loading dose: 10 mg/kg followed by a continuous IV infusion at 5 mg/kg/hour; dosing based on a pharmaco*kinetic model to achieve a target serum concentration of 20 mcg/mL; tranexamic acid must also be added to cardiopulmonary bypass solution at a concentration of 20 mcg/mL (Ref). A pharmaco*kinetic analysis (n=43; mean age: 123 days [range: 6 to 348 days]; mean weight: 4.95 kg [range: 2.3 to 9.5 kg]) targeting a serum concentration of 20 mcg/mL proposed the following regimen: Loading dose: 10 mg/kg, followed by a continuous IV infusion at 10 mg/kg/hour until initiation of cardiopulmonary bypass, then IV priming bolus: 4 mg/kg into the bypass prime volume, followed by a continuous IV infusion at 4 mg/kg/hour (Ref). Another regimen studied in 2 trials (n=80; age range: 2 months to 15 years) is 10 mg/kg into the bypass circuit after induction, during cardiopulmonary bypass, and after protamine reversal of heparin for a total of 3 doses (Ref). A pharmaco*kinetic analysis has proposed the following regimen to achieve a target serum concentration range of 20 to 30 mcg/mL in children 1 to 12 years and weighing 5 to 40 kg: IV: Loading dose: 6.4 mg/kg over 5 minutes followed by a weight-adjusted continuous IV infusion in the range of 2 to 3.1 mg/kg/hour; the pharmaco*kinetic data showed that patients weighing less should receive an initial continuous IV infusion rate at the higher end of the range (ie, if patient weight=5 kg then initial continuous IV infusion rate: 3.1 mg/kg/hour; if patient weight=40 kg then initial continuous IV infusion rate: 2 mg/kg/hour) (Ref).Intermediate dose: IV: Loading dose: 30 mg/kg followed by a continuous IV infusion at 10 mg/kg/hour; dosing based on a pharmaco*kinetic model to achieve a target serum concentration of 70 mcg/mL; tranexamic acid must also be added to cardiopulmonary bypass solution at a concentration of 70 mcg/mL (Ref).High dose: IV: Loading dose: 50 mg/kg, followed by a continuous IV infusion at 15 mg/kg/hour and 50 mg/kg priming dose into the circuit when bypass initiated (Ref); dosing based on a pharmaco*kinetic model to achieve a target serum concentration of 150 mcg/mL (Ref).Spinal surgery (eg, idiopathic scoliosis): Children ≥8 years and Adolescents: IV: Loading dose: 100 mg/kg, followed by a continuous IV infusion at 10 mg/kg/hour until skin closure (Ref). Other reported regimens with positive results: Loading dose: 20 mg/kg, followed by a continuous IV infusion at 10 mg/kg/hour (Ref); loading dose: 10 mg/kg, followed by a continuous IV infusion at 1 mg/kg/hour (Ref); loading dose: 50 mg/kg, followed by a continuous IV infusion at 5 mg/kg/hour (Ref).Craniosyntosis surgery: Infants ≥2 months and Children ≤6 years: IV: Loading dose: 50 mg/kg over 15 minutes prior to incision, followed by a continuous IV infusion at 5 mg/kg/hour until skin closure (Ref) or loading dose: 15 mg/kg over 15 minutes prior to incision, followed by a continuous IV infusion at 10 mg/kg/hour until skin closure (Ref). Other reported regimens with positive results: Loading dose: 10 mg/kg at start of surgery, followed by a continuous IV infusion at 5 mg/kg/hour for 24 hours postoperatively (Ref).Trauma, hemorrhagicTrauma, hemorrhagic (acute traumatic coagulopathy): Limited data available: Note: Reported regimens are variable and ideal dose-response is not established:Children <12 years: IV: Loading dose: 15 mg/kg over 10 minutes given within 3 hours of injury (maximum dose: 1,000 mg/dose), followed by continuous IV infusion at 2 mg/kg/hour for ≥8 hours or until bleeding stops (Ref).Children ≥12 years and Adolescents: IV: Loading dose: 1,000 mg over 10 minutes given within 3 hours of injury, followed by 1,000 mg infused over 8 hours (Ref).Traumatic hyphemaTraumatic hyphema: Limited data available: Children and Adolescents: Oral: 25 mg/kg/dose every 8 hours for 5 to 7 days (Ref). Note: This same regimen may also be used for secondary hemorrhage after an initial traumatic hyphema event.Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricNote: Recommendations are dependent on use and route.Oral:Menorrhagia: Female Children ≥12 years and Adolescents:Scr >1.4 to ≤2.8 mg/dL: 1,300 mg twice daily for up to 5 days during monthly menstruation.Scr >2.8 to ≤5.7 mg/dL: 1,300 mg once daily for up to 5 days during monthly menstruation.Scr >5.7 mg/dL: 650 mg once daily for up to 5 days during monthly menstruation.Prophylaxis of hereditary angioedema: Children and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, due to risk of accumulation with kidney impairment, dosage adjustments are recommended (Ref).IV:Tooth extraction in patients with hemophilia: Infants, Children, and Adolescents:Scr 1.36 to ≤2.83 mg/dL: Maintenance dose of 10 mg/kg/dose twice daily.Scr >2.83 to ≤5.66 mg/dL: Maintenance dose of 10 mg/kg/dose once daily.Scr >5.66 mg/dL: Maintenance dose of 10 mg/kg/dose every 48 hours or 5 mg/kg/dose every 24 hours.Prophylaxis or treatment of mild to major bleeding secondary to trauma or surgery: Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, due to risk of accumulation with kidney impairment, dosage adjustments are recommended (Ref).Dosing: Hepatic Impairment: PediatricInfants, Children, and Adolescents: No adjustment is necessary.Dosing: Adult(For additional information see "Tranexamic acid: Drug information")The adult dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editor: Edith A Nutescu, PharmD, MS, FCCP.Note: Safety: Higher total IV doses (eg, ≥50 mg/kg), such as those given perioperatively, may be associated with an increased risk of seizures; lower doses (eg, 1 or 2 g given in the first 8 hours of trauma) do not appear to increase the risk of seizure or venous thromboembolism (Ref).Abnormal uterine bleeding, nonacuteAbnormal uterine bleeding, nonacute (alternative agent): Note: Alternative for patients who decline or should not use hormonal therapy. Start at onset of heavy menstrual bleeding.Oral:Lysteda: 1.3 g 3 times daily for up to 5 days during monthly menstruation.Cyklokapron [Canadian product]: 1 to 1.5 g 3 to 4 times daily for up to 5 days during menstruation (Ref).Dental procedures in patients on oral anticoagulant therapyDental procedures in patients on oral anticoagulant therapy (off-label use):Oral rinse: 5% solution (extemporaneously prepared): Administer 5 to 10 minutes prior to the procedure; hold 5 to 10 mL in mouth and rinse for 2 minutes; drain gently, being careful not to forcibly spit and dislodge clots; do not eat or drink for 1 hour after using oral rinse. Repeat 3 to 4 times daily for 1 to 2 days after the procedure (Ref).Hemoptysis, treatmentHemoptysis (nonmassive), treatment (off-label use):Inhalation for nebulization: 500 mg (using injectable solution) 3 times daily for up to 5 days (Ref).Hereditary angioedema, long-term prophylaxisHereditary angioedema, long-term prophylaxis (alternative agent) (off-label use):Note: May be used when other agents (eg, C1 inhibitor, human monoclonal antibody) are not available or contraindicated (Ref).Oral: Initial: 500 to 650 mg two to three times daily; titrate gradually based on response and tolerability; usual daily dose: 3 g/day (Ref).Hereditary hemorrhagic telangiectasia, epistaxis or other bleeding sitesHereditary hemorrhagic telangiectasia, epistaxis or other bleeding sites (alternative agent) (off-label use): Note: May be used in carefully selected patients in whom local therapy and other management options are insufficient.Oral: Initial: 1.5 g twice daily or 1 g three times daily for 4 to 10 days; adjust dose as needed based on response and tolerability to a usual daily dose of 2 to 4.5 g in 2 or 3 divided doses (Ref).Intracranial hemorrhage associated with thrombolytic treatmentIntracranial hemorrhage associated with thrombolytic treatment (alternative agent) (off-label use): Note: Consider for use in addition to cryoprecipitate or when cryoprecipitate is contraindicated in patients who have a symptomatic intracranial hemorrhage after receiving thrombolytic within the past 24 hours (Ref).IV: 1 g (or 10 to 15 mg/kg) once; administer at a rate not to exceed 100 mg/minute (generally over 10 to 20 minutes) (Ref).Perioperative prevention of blood loss and transfusionPerioperative prevention of blood loss and transfusion (eg, cardiac surgery, other surgeries with significant blood loss):Note: There is wide variety in doses and routes of administration (IV, oral, and/or topical). Dosing and timing of administration are procedure and institution specific. Recommendations provided below are examples of IV regimens for use in selected surgeries; refer to institutional protocols.Usual dose and range: IV: 1 g (or 10 to 30 mg/kg) prior to procedure; administer at a rate not to exceed 100 mg/minute (generally over 10 to 30 minutes). Depending upon type of procedure, a continuous infusion may be given intraoperatively after the initial bolus dose, or the bolus dose may be repeated at the end of procedure and/or during the postoperative period (Ref).Cardiac surgery (off-label use):Note: Optimal regimen is uncertain; refer to institutional protocol.IV: Loading dose: 10 to 30 mg/kg administered at a rate not to exceed 100 mg/minute (generally over 10 to 20 minutes), followed by 1 to 16 mg/kg/hour (Ref). Alternatively, some centers administer a single loading dose of 50 mg/kg (Ref).Orthopedic surgery (hip or knee arthroplasty) (off-label use):Note: Optimal regimen is uncertain; refer to institutional protocol. Use in patients without a baseline high risk of thromboembolism. For patients with risk factors for thromboembolism, consider risk of thromboembolism vs benefit of reduced blood loss (Ref).IV: 1 g (or 10 to 15 mg/kg) administered before skin incision at a rate not to exceed 100 mg/minute (generally over 10 to 20 minutes); repeat dose at skin closure or up to 12 hours later; some experts recommend a third dose during the postoperative period if needed (Ref). Note: Some experts use intra-articular tranexamic acid (ie, 1 g per 50 mL of NS applied topically into the wound at the end of the procedure) (Ref).Spinal surgery (eg, spinal fusion) (off-label use):Note: Optimal regimen is uncertain; refer to institutional protocol.IV: 10 to 15 mg/kg administered prior to incision at a rate not to exceed 100 mg/minute (generally over 10 to 20 minutes), followed by 1 to 2 mg/kg/hour as a continuous infusion for the remainder of the surgery; discontinue at the end of the procedure (Ref).Postpartum hemorrhage, preventionPostpartum hemorrhage, prevention (adjunctive agent) (off-label use): Note: For use in patients in high bleeding risk situations in conjunction with standard prophylactic uterotonics (eg, oxytocin) (Ref).IV: 1 g (or 10 to 15 mg/kg) over 10 to 20 minutes (Ferrari 2022; Saccone 2019); may administer before skin incision for cesarean deliveries and after cord clamping for vagin*l deliveries (Ref).Postpartum hemorrhage, treatmentPostpartum hemorrhage, treatment (adjunctive agent) (off-label use): Note: For continued bleeding despite oxytocin; used in conjunction with other therapies/procedures.IV: 1 g over 10 to 20 minutes given within 3 hours of vagin*l birth or cesarean delivery. If bleeding continues after 30 minutes, may repeat the dose in conjunction with thorough re-evaluation for cause of continued or recurrent bleeding (Ref).Tooth extraction in patients with hemostatic defectsTooth extraction in patients with hemostatic defects (eg, hemophilia, von Willebrand disease, other factor deficiencies associated with bleeding) (adjunctive agent):Note: Generally used in conjunction with (and not as a substitute for) replacement of the appropriate clotting factor, especially in individuals with hemophilia. Do not give simultaneously with an activated prothrombin complex concentrate, as this can increase the risk of thromboembolism; if used concurrently, separate by ≥12 hours (Ref). Consultation with a hemophilia treatment center is advised.IV: 10 mg/kg using actual body weight (usual dose range: 500 mg to 1 g) administered ~2 hours before procedure at a rate not to exceed 100 mg/minute (generally over 10 to 20 minutes), then 10 mg/kg 3 to 4 times daily for 2 to 8 days. Alternatively, 10 mg/kg as a single dose ~2 hours prior to procedure; following procedure, transition to oral tranexamic acid depending on individual patient characteristics, type of procedure, other therapies, and degree of bleeding (Ref).Oral: 25 mg/kg (usual dose range: 1 to 1.5 g) given 2 hours prior to procedure, then 25 mg/kg (usual dose range: 1 to 1.5 g) 3 to 4 times daily for up to 7 to 10 days (Ref).Trauma-associated hemorrhage or traumatic brain injuryTrauma-associated hemorrhage or traumatic brain injury (off-label use):Note: Consider for use in patients with significant hemorrhage, at risk of significant hemorrhage, or in moderate traumatic brain injury (TBI) (Glasgow Coma Scale [GCS] score >8 and <13); patients with severe TBI (GCS score 3 to 8) may not demonstrate benefit (Ref).IV: Loading dose: 1 g over 10 minutes started within 3 hours of injury, followed by 1 g over the next 8 hours as a continuous infusion. Note: Some experts suggest using thromboelastogram or rotational thromboelastometry to guide therapy (Ref).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultThe renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.Note: Tranexamic acid is >95% eliminated by the kidney. Dosing recommendations may vary by institution; also consult institutional protocols. No dosage adjustment necessary for indications requiring only 1 to 2 doses (Ref). Tranexamic acid oral rinses have limited absorption (Ref); therefore, the need for renal dose adjustment is unlikely when used for a limited period of time (Ref). There are no data on bioavailability of tranexamic acid administered via nebulization; renal dose adjustment recommendations cannot be provided; use with caution (Ref).Altered kidney function:IV:Intermittent injection (Ref): Note: The following adjustments are based on a usual recommended dose of 10 mg/kg or 1 g 3 to 4 times daily.Serum creatinine <1.4 mg/dL (<120 micromol/L): No dosage adjustment necessary.Serum creatinine ≥1.4 to <2.8 mg/dL (≥120 micromol/L to <250 micromol/L): Administer usual dose twice daily.Serum creatinine ≥2.8 to <5.7 mg/dL (≥250 to <500 micromol/L): Administer usual dose once daily.Serum creatinine ≥5.7 mg/dL (≥500 micromol/L): Administer usual dose every 48 hours or 50% of the usual dose once daily.Continuous infusion:General recommendations (Ref): Note: Developed using the principal that % to be administered is (actual GFR divided by normal GFR) × 100%, with normal GFR = 90 mL/minute/1.73 m2. Recommendations should only be considered for cardiac or spinal indications; not applicable to trauma patients (Ref).Maintenance infusion following loading dose:eGFR ≥90 mL/minute/1.73 m2: Administer 100% of the usual maintenance rate.eGFR 60 to <90 mL/minute/1.73 m2: Administer 66% to 100% of the usual maintenance rate.eGFR ≥30 to <60 mL/minute/1.73 m2: Administer 33% to 66% of the usual maintenance rate.eGFR <30 mL/minute/1.73 m2: Administer 17% to 33% of the usual maintenance rate.Cardiac surgery regimen-specific examples: Note: These are examples of published regimens utilizing a continuous infusion; optimal regimen is uncertain; also refer to institutional protocol.eGFR-based regimen (BART regimen) (Ref): eGFR ≥90 mL/minute/1.73 m2: Loading dose: 30 mg/kg followed by 16 mg/kg/hour.eGFR 60 to <90 mL/minute/1.73 m2: Loading dose: 30 mg/kg followed by 11 to 16 mg/kg/hour.eGFR >30 to <60 mL/minute/1.73 m2: Loading dose: 25 to 30 mg/kg followed by 5 to 10 mg/kg/hour.eGFR ≤30 mL/minute/1.73 m2: Loading dose: 25 to 30 mg/kg followed by 3 to 5 mg/kg/hour.Serum creatinine-based regimen (Ref):Serum creatinine 1.6 to 3.3 mg/dL: Reduce maintenance infusion to 1.5 mg/kg/hour (based on a 25% reduction from 2 mg/kg/hour).Serum creatinine 3.3 to 6.6 mg/dL: Reduce maintenance infusion to 1 mg/kg/hour (based on a 50% reduction from 2 mg/kg/hour).Serum creatinine >6.6 mg/dL: Reduce maintenance infusion to 0.5 mg/kg/hour (based on a 75% reduction from 2 mg/kg/hour).Oral (Ref): Note: The following adjustments are based on a usual recommended dose of 10 to 15 mg/kg or 1 to 1.5 g 3 to 4 times daily.Serum creatinine <1.4 mg/dL (<120 micromol/L): No dosage adjustment necessary.Serum creatinine ≥1.4 to <2.8 mg/dL (≥120 to <250 micromol/L): Administer usual dose twice daily.Serum creatinine ≥2.8 to <5.7 mg/dL (≥250 to <500 micromol/L): Administer usual dose once daily.Serum creatinine ≥5.7 mg/dL (≥500 micromol/L): Administer usual dose every 48 hours, or 50% of the usual dose every 24 hours.Hemodialysis, intermittent (thrice weekly): Likely to be dialyzable (low protein binding, low Vd (Ref)): Note: Because tranexamic acid is dialyzable, schedule intermittent doses after hemodialysis when possible.IV (intermittent injection), Oral: Administer usual dose every 48 hours, or 50% of the usual dose every 24 hours (Ref).IV (continuous infusion): Dose as for eGFR <30 mL/minute/1.73 m2 (Ref).Peritoneal dialysis: Likely to be dialyzable (low protein binding, low Vd (Ref)).IV (intermittent injection), Oral: Administer usual dose every 48 hours, or 50% of the usual dose every 24 hours (Ref).IV (continuous infusion): Dose as for eGFR <30 mL/minute/1.73 m2 (Ref).CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Close monitoring of response and adverse reactions (eg, seizures, thrombotic events) due to drug accumulation is important.IV (intermittent injection), Oral: Administer usual dose twice daily (Ref).IV (continuous infusion): Dose as for eGFR 30 to 60 mL/minute/1.73 m2 (Ref).PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and adverse reactions (eg, seizures, thrombotic events) due to drug accumulation is important.IV (intermittent injection), Oral: Administer usual dose twice daily (Ref).IV (continuous infusion): Dose as for eGFR 30 to 60 mL/minute/1.73 m2 (Ref).Dosing: Hepatic Impairment: AdultNo dosage adjustment is necessary.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution, Intravenous: Generic: 1000 mg/10 mL (10 mL)Solution, Intravenous [preservative free]: Cyklokapron: 1000 mg/10 mL (10 mL)Generic: 1000 mg/10 mL (10 mL); 1000 mg/100 mL in NaCl 0.7% (100 mL)Tablet, Oral: Lysteda: 650 mgGeneric: 650 mgGeneric Equivalent Available: USYesDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution, Intravenous: Cyklokapron: 100 mg/mL (5 mL, 10 mL)Generic: 100 mg/mL (5 mL, 10 mL, 50 mL); 1000 mg/10 mL (10 mL)Tablet, Oral: Cyklokapron: 500 mgGeneric: 500 mgAdministration: PediatricOral: Administer without regard to meals; tablets should be swallowed whole; do not break, split, chew, or crush.Parenteral:Intermittent IV dose: May be administered undiluted by direct IV injection at a maximum rate of 100 mg/minute; faster rates may cause hypotension.Continuous IV infusion:Loading dose: May be administered either undiluted or diluted in a compatible diluent; infuse over 5 to 15 minutes (Ref). Neonatal patients received loading doses over 60 minutes (Ref).IV infusion: Following dilution, administer by continuous IV infusion at a rate not to exceed 100 mg/minute.Inhalation: Administer undiluted (100 mg/mL) by jet nebulization (Ref); time for nebulization average 15 minutes in adults (Ref).Administration: AdultInhalation via nebulization (off-label use/route): Administer over 15 minutes via jet nebulizer (Ref).Injection: For indications requiring a loading dose (eg, trauma-associated hemorrhage, perioperative prevention of blood loss and transfusion), may administer undiluted by IV injection at a maximum rate of 100 mg/minute (Ref); faster rates may cause hypotension. For continuous IV infusions, dilute with compatible solutions and administer at a rate not to exceed 100 mg/minute.When used for the prevention of postpartum hemorrhage (off-label use), tranexamic acid can be infused before skin incision (cesarean deliveries) or after cord clamping (cesarean or vagin*l deliveries) (Ref).Oral: Administer without regard to meals. Swallow tablet whole; do not break, chew, or crush.Storage/StabilityIV:Ampules and vials: Store intact ampules and vials at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Diluted mixture may be stored for up to 4 hours at room temperature. However, solutions prepared in NS are chemically stable for up to 180 days at room temperature (McCluskey 2014). In another study, tranexamic acid (undiluted) was shown to be chemically stable for up to 12 weeks when stored at -20°C, 4°C, 22°C, and 50°C; freezing tranexamic acid in original ampules is unacceptable due to cracking of the ampules (de Guzman 2013). Freezing tranexamic acid in original vials has not been evaluated.Premixed solution: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).Tablets: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).UseOral: Tablet (Lysteda): Treatment of cyclic heavy menstrual bleeding (menorrhagia) (FDA approved in postmenarche females); has also been used in the prevention of hereditary angioedema attacks (HAE) (long and short term) and for management of traumatic hyphema.Parenteral: Short-term use (2 to 8 days) in hemophilia patients to reduce or prevent hemorrhage and reduce need for replacement therapy during and following tooth extraction (FDA approved in pediatric patients [age not specified] and adults); has also been used to decrease perioperative blood loss and the need for transfusion in patients undergoing congenital heart disease corrective surgery, scoliosis-related surgery, craniosynostosis surgery, and congenital diaphragmatic hernia repair with extracorporeal membrane oxygenation; to reduce transfusion requirements in trauma patients; and to treat intractable diffuse alveolar hemorrhage.Medication Safety IssuesSound-alike/look-alike issues:Cyklokapron may be confused with cycloSPORINETXA (occasional abbreviation for tranexamic acid) is an error-prone abbreviation (mistaken as TNK an error-prone abbreviation for tenecteplase and tPA an error-prone abbreviation for alteplase)Administration issues:Inadvertent administration of tranexamic acid by the epidural or spinal route during neuraxial (eg, epidural, spinal) anesthesia has led to potentially fatal neurotoxic adverse reactions. Carefully evaluate storage procedures within the surgical suite, including separating tranexamic acid from local anesthetics; consider additional prevention measures, including purchasing, dispensing, and administration (ISMP [Smetzer] 2019; NAN Alert 2020; Patel 2019).Adverse Reactions (Significant): ConsiderationsHypersensitivity reactions (immediate and delayed)Immediate hypersensitivity reactions (eg, anaphylaxis) have been reported, ranging from mild pruritus and/or urticaria to more severe reactions, including angioedema, wheezing, hypotension, and anaphylactic shock (Ref). Delayed hypersensitivity reactions include fixed drug eruption and toxic epidermal necrolysis (TEN) (Ref).Mechanism: Immediate hypersensitivity reactions (eg, anaphylaxis, urticaria): Non–dose-related, immunologic, IgE-mediated. Delayed hypersensitivity reactions: Non–dose-related, immunologic, T-cell mediated (Ref).Onset: Immediate hypersensitivity reactions: Rapid; occur within 1 hour of administration but may occur up to 6 hours after exposure (Ref). Delayed hypersensitivity reactions: Varied; serious cutaneous adverse reactions, including TEN, occur 1 to 8 weeks after initiation (Ref).Ocular effectsVisual defects (eg, vision color changes, visual impairment, vision loss), retinal artery occlusion, and retinal venous occlusion have been reported (Ref). Conjunctivitis (ligneous), a form of membranous conjunctivitis, has been reported with the oral formulation but resolved upon discontinuation of therapy (Ref).Mechanism: Visual defects: Unknown (Ref). Ligneous conjunctivitis: Unknown; likely vasculopathy with increased vessel permeability and consequent loss of protein (Ref). Onset: Visual defects: Varied; retinal artery occlusion occurred 5 days to 1 month after initiation (Ref). Ligneous conjunctivitis: Varied; occurred 1 to 9 months after initiation; upon reintroduction, occurred within 2 days (Ref).Risk factors:• Kidney failure (Ref)Seizures and myoclonusSeizures have been reported, typically generalized tonic-clonic; although, focal and mixed seizures may also occur (Ref). Myoclonus is noted in ~20% of patients. Seizures usually persist for a few minutes and rarely progress to status epilepticus (Ref). Recurrent seizures may occur in 30% to 60% of patients during the first 24 to 48 hours after postoperative administration (Ref). The incidence of seizures is ~2.7% (Ref).Mechanism: Dose-related: Unknown; may occur due to antagonistic effect of tranexamic acid at GABA-A receptors and neural glycine receptors, resulting in lowered seizure threshold; cerebral emboli may also play a role (Ref).Onset: Rapid; within the first 5 to 8 hours after postoperative administration (Ref). Risk factors:• Higher intravenous doses may increase risk (Ref); although, one study showed no increased risk of seizure with high dose versus low dose (Ref)• Cardiac surgery, in particular patients undergoing open heart surgery; deep hypothermic circulatory arrest, increased cardiopulmonary bypass time, or prolonged aortic cross-clamp time are also associated with increased risk in this population (Ref)• Females (Ref)• Increased age (>70 years) (Ref)• Poor overall health (Ref)• Kidney impairment (Ref)• Prior neurological and cardiovascular disorders (Ref)• History of stroke (Ref)Thromboembolic eventsVenous thromboembolism and arterial thromboembolism, including deep vein thrombosis, pulmonary embolism, retinal vein occlusion, and retinal artery occlusion, have been reported (Ref). The incidence of thromboembolism after various surgical procedures has been reported from 0.3% to 8.2% (Ref). In contrast, some studies have shown no significant increase in thromboembolism risk (Ref).Mechanism: Dose-related; unknown; reversibly displaces plasminogen from fibrin, resulting in the cessation of fibrinolysis (Ref). May also inhibit the proteolytic activity of plasmin (Ref).Onset: Varied; may occur within 1 hour (Ref), up to several years after initiation (Ref).Risk factors: • High doses (≥20 mg/kg) or 2 to 4 g (Ref)• Variceal bleeding or liver disease (Ref)• Increased age (Ref)• Cardiovascular disease (Ref)• History of or active thromboembolic disease• Concurrent procoagulant agents (eg, prothrombin complex concentrate, oral tretinoin, hormonal contraceptives)Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. As reported with oral formulation unless otherwise noted.>10%:Gastrointestinal: Abdominal pain (20%)Nervous system: Headache (50%)Neuromuscular & skeletal: Back pain (21%), musculoskeletal pain (11%)Respiratory: Nasal signs and symptoms (25%; including sinus symptoms)1% to 10%:Hematologic & oncologic: Anemia (6%)Nervous system: Fatigue (5%)Neuromuscular & skeletal: Arthralgia (7%), muscle cramps (≤7%), muscle spasm (≤7%)Postmarketing (all formulations):Cardiovascular: Arterial thromboembolism (Meaidi 2021), deep vein thrombosis (HALT-IT 2020), hypotension (with rapid IV injection), pulmonary embolism (HALT-IT 2020; Ijaopo 2020), venous thromboembolism (HALT-IT 2020)Dermatologic: Allergic dermatitis (Imbesi 2010), fixed drug eruption (Kaku 2014), pruritus (Imbesi 2010), toxic epidermal necrolysis (Pretel Irazabal 2013), urticaria (Imbesi 2010)Gastrointestinal: Diarrhea, nausea, vomitingHypersensitivity: Anaphylactic shock, anaphylaxis (El Hanache 2021), angioedema (Imbesi 2010), nonimmune anaphylaxisNervous system: Cerebral thrombosis, dizziness, myoclonus (Lecker 2016), seizure (Lecker 2016)Ophthalmic: Chromatopsia, conjunctivitis (ligneous) (Song 2014), retinal artery occlusion (Wijetilleka 2017), retinal vein occlusion, vision color changes (Kiser 2021), vision loss (Wijetilleka 2017), visual impairment (Kitamura 2003)Renal: Renal cortical necrosis (Ko 2017)Respiratory: Wheezing (Murdaca 2020)ContraindicationsHypersensitivity to tranexamic acid or any component of the formulation.Injection: Active intravascular clotting; subarachnoid hemorrhage.Oral: Active thromboembolic disease (eg, cerebral thrombosis, DVT, or pulmonary embolism); history of thrombosis or thromboembolism, including retinal vein or retinal artery occlusion; intrinsic risk of thrombosis or thromboembolism (eg, hypercoagulopathy, thrombogenic cardiac rhythm disease, thrombogenic valvular disease); patients using combined hormonal contraception who may become pregnant.Canadian labeling: Additional contraindications (not in the US labeling): Injection, oral: History or risk of thrombosis (unless concurrent anticoagulation therapy is possible); hematuria; epidural administration; intrathecal administration.Warnings/PrecautionsConcerns related to adverse effects:• CNS effects: May cause dizziness, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).Disease-related concerns:• Disseminated intravascular coagulation: Use with extreme caution in patients with disseminated intravascular coagulation requiring antifibrinolytic therapy; patients should be under strict supervision of a health care provider experienced in treating this disorder.• Renal impairment: Use with caution in patients with renal impairment; dosage modification necessary.• Subarachnoid hemorrhage: Use with caution in patients with subarachnoid hemorrhage; cerebral edema and infarction may occur.• Vascular disease: Use with caution in patients with uncorrected cardiovascular or cerebrovascular disease due to the complications of thrombosis.Metabolism/Transport EffectsNone known.Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions programAnti-inhibitor Coagulant Complex (Human): Antifibrinolytic Agents may enhance the thrombogenic effect of Anti-inhibitor Coagulant Complex (Human).Risk X: Avoid combinationEstrogen Derivatives: May enhance the thrombogenic effect of Tranexamic Acid. Risk X: Avoid combinationFactor IX Complex (Human) [(Factors II, IX, X)]: Antifibrinolytic Agents may enhance the adverse/toxic effect of Factor IX Complex (Human) [(Factors II, IX, X)]. Specifically, the risk for thrombosis may be increased.Risk X: Avoid combinationHormonal Contraceptives: May enhance the thrombogenic effect of Tranexamic Acid. Risk X: Avoid combinationProthrombin Complex Concentrate (Human) [(Factors II, VII, IX, X), Protein C, and Protein S]: Antifibrinolytic Agents may enhance the adverse/toxic effect of Prothrombin Complex Concentrate (Human) [(Factors II, VII, IX, X), Protein C, and Protein S]. Specifically, the risk for thrombosis may be increased.Risk X: Avoid combinationThrombolytic Agents: Tranexamic Acid may diminish the therapeutic effect of Thrombolytic Agents. Thrombolytic Agents may diminish the therapeutic effect of Tranexamic Acid.Risk X: Avoid combinationTretinoin (Systemic): May enhance the thrombogenic effect of Antifibrinolytic Agents. Management: Concomitant use of antifibrinolytics and tretinoin is not recommended. If combined, monitor patients closely for any signs of thrombotic complications. Risk D: Consider therapy modificationReproductive ConsiderationsTranexamic acid is an alternative agent for the treatment of heavy menstrual bleeding and one option for patients who desire future fertility (ACOG 2019). The manufacturer recommends non-hormonal contraception during treatment, as hormonal contraceptives may increase the risk of thromboembolic events (use of hormonal contraception is contraindicated by some manufacturers). However, tranexamic acid in combination with oral contraceptives may be considered for the treatment of heavy menstrual bleeding when monotherapy is ineffective and other treatment options have failed (ACOG 2013; ACOG 2019).Pregnancy ConsiderationsTranexamic acid crosses the placenta; concentrations within cord blood are similar to maternal serum.Due to pregnancy-induced physiologic changes, some pharmaco*kinetic properties of oral tranexamic acid may be altered (Muhunthan 2020).Oral tranexamic acid is used off label for the long-term prophylaxis of hereditary angioedema (HAE) and use for this indication in pregnant patients has been reported (González-Quevedo 2016; Machado 2017; Milingos 2009). Tranexamic acid is not the preferred therapy for HAE in pregnant patients. Use may be considered for long-term prophylaxis of HAE during pregnancy when preferred treatment is not available; however, efficacy data are not available (US HAEA [Busse 2021]; WAO/EEACI [Maurer 2022]).IV tranexamic acid is used off label for the treatment of postpartum hemorrhage (PPH) (Ducloy-Bouthors 2011; RCOG [Pavord 2017]; WOMAN Trial Collaborators 2017). A significant reduction in risk of death due to bleeding was observed when treatment was started within 3 hours of vagin*l birth or cesarean section (WOMAN Trial Collaborators 2017). Tranexamic acid is recommended for the treatment of obstetric hemorrhage when initial medical management fails (ACOG 2017; WHO 2017).IV tranexamic acid has also been studied for prophylaxis of PPH in patients prior to vagin*l or cesarean delivery (Novikova 2015; Saccone 2019; Sentilhes 2018; Sentilhes 2021; Simonazzi 2016; Xia 2020). Tranexamic acid may be considered as adjunctive therapy in patients at high risk for PPH. Patients at high risk include those with a known coagulation defect; bleeding upon admission; hematocrit <30%; history of PPH; abnormal vital signs (hypotension and tachycardia); or placenta previa, accreta, increta, or percreta. However, available data related to prophylactic use are insufficient, and use for routine prophylaxis against PPH is not currently recommended outside of the context of clinical research (ACOG 2017; Muñoz 2019). Additional studies may be needed to define the optimal dose (Ahmadzia 2021; Li 2021).When managing PPH, do not use tranexamic acid in patients with clear contraindications to therapy, including active intravascular clotting, known thromboembolic event during pregnancy, known hemostatic disorders, or known hypersensitivity to tranexamic acid (Ducloy-Bouthors 2011; Shakur 2010; WHO 2017).Monitoring ParametersOral: Signs or symptoms of hypersensitivity reactions and thrombotic events (including ocular), ophthalmic examination (visual acuity, color vision, eye-ground, and visual fields) at baseline and regular intervals during the course of therapy in patients being treated for longer than several days.Parenteral: Blood pressure, ophthalmic examination (visual acuity, color vision, eye-ground, and visual fields) at baseline and regular intervals during the course of therapy in patients being treated for longer than several days, signs or symptoms of hypersensitivity reactions, seizures, thrombotic events, and ureteral obstruction.Mechanism of ActionForms a reversible complex that displaces plasminogen from fibrin resulting in inhibition of fibrinolysis; it also inhibits the proteolytic activity of plasminWith reduction in plasmin activity, tranexamic acid also reduces activation of complement and consumption of C1 esterase inhibitor (C1-INH), thereby decreasing inflammation associated with hereditary angioedema. Pharmaco*kinetics (Adult data unless noted)Distribution: Vd: IV: 9 to 12 L; cerebrospinal fluid and aqueous humor of eye concentrations are 10% of plasma.Protein binding: ~3%, primarily to plasminogen.Bioavailability: Oral: ~45%.Half-life elimination: IV: ~2 hours; Oral: ~11 hours.Time to peak: Oral:Single dose: Mean: 2.5 hours (range: 1 to 5 hours).Multiple dose: Mean: 2.5 hours (range: 2 to 3.5 hours).Excretion: Urine (>95% as unchanged drug).Pharmaco*kinetics: Additional ConsiderationsAltered kidney function: Following administration of a single IV injection, urinary excretion declines as renal function decreases.Pediatric: The Cmax and AUC values after a single oral dose of 1,300 mg in adolescent females were 20% to 25% less than those in adult females given the same dose.In vitro data suggests that neonates require a lower serum tranexamic acid concentration than adults (6.54 mcg/mL vs 17.5 mcg/mL) to completely prevent fibrinolysis (Yee 2013). In pediatric patients weighing 5 to 40 kg undergoing cardiac surgery with by-pass, a target serum concentration range of 20 to 30 mcg/mL has been used in pharmaco*kinetic analysis (Dowd 2002; Grassin-Delyle 2013).Extemporaneous Preparations50 mg/mL (5%) Oral SolutionA 50 mg/mL (5%) oral solution may be prepared by diluting 5 mL of 10% (100 mg/mL) tranexamic acid injection with 5 mL sterile water. Label "refrigerate". Stable for 5 days refrigerated.Lam MS. Extemporaneous Compounding of Oral Liquid Dosage Formulations and Alternative Drug Delivery Methods for Anticancer Drugs. Pharmacotherapy. 2011;31(2):164-192.2127549525 mg/mL Oral Suspension A 25 mg/mL oral suspension may be prepared with tablets. Place one 500 mg tablet (strength not available in US) into 20 mL water and let stand ~2 to 5 minutes. Begin stirring and continue until the tablet is completely disintegrated, forming a fine particulate suspension (dispersion time for each 500 mg tablet is ~2 to 5 minutes). Administer immediately after preparation.Lam MS. Extemporaneous Compounding of Oral Liquid Dosage Formulations and Alternative Drug Delivery Methods for Anticancer Drugs. Pharmacotherapy. 2011;31(2):164-192.21275495Pricing: USSolution (Cyklokapron Intravenous)1000 mg/10 mL (per mL): $2.40Solution (Tranexamic Acid Intravenous)1000 mg/10 mL (per mL): $0.46 - $8.68Solution (Tranexamic Acid-NaCl Intravenous)1000MG/100ML 0.7% (per mL): $0.25Tablets (Lysteda Oral)650 mg (per each): $6.52Tablets (Tranexamic Acid Oral)650 mg (per each): $5.21 - $5.22Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalAmchafibrin (ES);Anaxyl (BD);Aneptil (LK);Azeptil (TR);Bionex (BD);Blonda (TW);Caprilon (FI);Ciclokapron (VE);Cyclokapron (BE, CL, IS, LU, MT);Cyklokapron (AE, AT, AU, BB, BH, CH, CY, DE, DK, EE, ET, FI, GB, IE, IQ, IR, JO, KW, LB, LY, NL, NO, NZ, OM, QA, SA, SE, SG, SY, YE, ZA, ZW);Duhemos (VN);Espercil (CL);Exacyl (AE, BE, CZ, FR, HN, LB, LU, PL);Fimoplas (PH);Gemaxam (UA);Gemotran (UA);Hemanex (PH);Hemoblock (EC);Hemoclot (PH);Hemokapron (EG);Hemostan (PH);Hemotrex (PH);Hexakapron (IL);Kalnex (ID);Lunex (ID);Lysteda (CR, DO, GT, HN, NI, PA, SV);Medsamic (VN);Morwak (ZA);Nexa (ID);Nobleed (LK);Oilexam (DK);Pilexam (NO);Qualixamin (HK);Ranexid (PH);Relcon (TW);Rikaparin (TW);Ronex (ID);Sangera (UA);Tiren (MY);Tosano (HK);Tracid (BD);Tramic (TH);Tranarest (IN);Tranex (BD, EG, IT);Tranexam (RU);Tranexid (ID);Tranic (ZA);Tranlok (LK);Tranmix (VN);Transamin (BR, CN, HK, JP, KR, MY, PK, TH, VN);Transamina (UY);Transic (TH);Tranxa (ID);Traxan (PH);Trenaxin (PH);Trenolk (HR);Trexacont (BR);Zamic (AU);Zucerin (TW)For country code abbreviations (show table)Aboul-Fotouh S, Habib MZ, Magdy SM, Hassan BEE. Tranexamic acid-associated fatal status epilepticus in a paediatric non-cardiac surgery: a case report and literature review. Br J Clin Pharmacol. 2022;88(9):4211-4216. doi:10.1111/bcp [PubMed 35244235]Ahmadzia HK, Luban NLC, Li S, et al. Optimal use of intravenous tranexamic acid for hemorrhage prevention in pregnant women. Am J Obstet Gynecol. 2021;225(1):85.e1-85.e11. doi:10.1016/j.ajog.2020.11.035 [PubMed 33248975]Alshryda S, Mason J, Sarda P, et al. Topical (intra-articular) tranexamic acid reduces blood loss and transfusion rates following total hip replacement: a randomized controlled trial (TRANX-H). J Bone Joint Surg Am. 2013a;95(21):1969-1974. doi:10.2106/JBJS.L.00908 [PubMed 24196467]Alshryda S, Mason J, Vaghela M, et al. Topical (intra-articular) tranexamic acid reduces blood loss and transfusion rates following total knee replacement: a randomized controlled trial (TRANX-K). J Bone Joint Surg Am. 2013b;95(21):1961-1968. doi:10.2106/JBJS.L.00907 [PubMed 24196466]American College of Obstetricians and Gynecologists (ACOG). ACOG Committee Opinion No. 557: Management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women. Obstet Gynecol. 2013;121(4):891-896. doi:10.1097/01.AOG.0000428646.67925.9a [PubMed 23635706]American College of Obstetricians and Gynecologists (ACOG). ACOG Committee Opinion No. 785: Screening and management of bleeding disorders in adolescents with heavy menstrual bleeding. Obstet Gynecol. 2019;134(3):e71-e83. doi:10.1097/AOG.0000000000003411 [PubMed 31441825]American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins—Obstetrics. Practice Bulletin No. 183: Postpartum hemorrhage. Obstet Gynecol. 2017;130(4):e168-e186. doi:10.1097/AOG.0000000000002351 [PubMed 28937571]Amundson AW, Johnson RL. Anesthesia for total knee arthroplasty. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 25, 2022.Andersson L, Eriksson O, Hedlund PO, Kjellman H, Lindqvist B. Special considerations with regard to the dosage of tranexamic acid in patients with chronic renal diseases. Urol Res. 1978;6(2):83-88. doi:10.1007/BF00255578 [PubMed 664136]Based on expert opinion.Bafaqih H, Chehab M, Almohaimeed S, et al. Pilot trial of a novel two-step therapy protocol using nebulized tranexamic acid and recombinant factor VIIa in children with intractable diffuse alveolar hemorrhage. Ann Saudi Med. 2015;35(3):231‐239. [PubMed 26409798]Baskaran D, Rahman S, Salmasi Y, Froghi S, Berber O, George M. Effect of tranexamic acid use on blood loss and thromboembolic risk in hip fracture surgery: systematic review and meta-analysis. Hip Int. 2018;28(1):3-10. doi:10.5301/hipint.5000556 [PubMed 28983887]Bellón T. Mechanisms of severe cutaneous adverse reactions: recent advances. Drug Saf. 2019;42(8):973-992. doi:10.1007/s40264-019-00825-2 [PubMed 31020549]Beno S, Ackery AD, Callum J, Rizoli S. Tranexamic acid in pediatric trauma: why not?. Crit Care. 2014;18(4):313. [PubMed 25043066]Berghella V. Management of the third stage of labor after vagin*l delivery: drug therapy to minimize hemorrhage. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 23, 2021.Bernardo E, Anders M, Schmees L, Resendiz K. Inhaled tranexamic acid for pulmonary hemorrhage in critically ill pediatric patients. Critical Care Medicine. 2019;47(1):577. [PubMed 32166295]Bérubé C. Factor XI (eleven) deficiency. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 13, 2021.Borea G, Montebugnoli L, Capuzzi P, Magelli C. Tranexamic acid as a mouthwash in anticoagulant-treated patients undergoing oral surgery. An alternative method to discontinuing anticoagulant therapy. Oral Surg Oral Med Oral Pathol. 1993;75(1):29-31. doi:10.1016/0030-4220(93)90401-o [PubMed 8419869]Bowen T, Cicardi M, Farkas H, et al. Canadian 2003 international consensus algorithm for the diagnosis, therapy, and management of hereditary angioedema. J Allergy Clin Immunol. 2004;114(3):629‐637. [PubMed 15356569]Bowen T, Cicardi M, Farkas H, et al. 2010 international consensus algorithm for the diagnosis, therapy and management of hereditary angioedema. Allergy Asthma Clin Immunol. 2010;6(1):24. doi:10.1186/1710-1492-6-24 [PubMed 20667127]Brockow K, Przybilla B, Aberer W, et al. Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM). Allergo J Int. 2015;24(3):94-105. doi:10.1007/s40629-015-0052-6 [PubMed 26120552]Brown MJ. Anesthesia for elective spine surgery in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 23, 2021.Busse PJ, Christiansen SC, Riedl MA, et al. US HAEA Medical Advisory Board 2020 guidelines for the management of hereditary angioedema. J Allergy Clin Immunol Pract. 2021;9(1):132-150.e3. doi:10.1016/j.jaip.2020.08.046 [PubMed 32898710]Callum JL, Yeh CH, Petrosoniak A, et al. A regional massive hemorrhage protocol developed through a modified Delphi technique. CMAJ Open. 2019;7(3):E546-E561. doi:10.9778/cmajo.20190042 [PubMed 31484650]Carroll ND, Restrepo CS, Eastridge BJ, Stasik CN. Left atrial thrombi following tranexamic acid in a bleeding trauma patient-A word of caution. J Card Surg. 2018;33(2):83-85. doi:10.1111/jocs.13521 [PubMed 29385649]Carter G, Goss A. Tranexamic Acid Mouthwash -- A Prospective Randomized Study of a 2-Day Regimen vs 5-Day Regimen to Prevent Postoperative Bleeding in Anticoagulated Patients Requiring Dental Extractions. Int J Oral Maxillofac Surg. 2003;32(5):504-7. [PubMed 14759109]Chauhan S, Bisoi A, Kumar N, et al. Dose Comparison of Tranexamic Acid in Pediatric Cardiac Surgery. Asian Cardiovasc Thorac Ann. 2004a;12(2):121-124. [PubMed 15213077]Chauhan S, Das SN, Bisoi A, et al. Comparison of Epsilon Aminocaproic Acid and Tranexamic Acid in Pediatric Cardiac Surgery. J Cardiothorac Vasc Anesth. 2004b;18(2):141-143. [PubMed 15073700]Choi WS, Irwin MG, Samman N. The Effect of Tranexamic Acid on Blood Loss During Orthognathic Surgery: A Randomized Controlled Trial. J Oral Maxillofac Surg. 2009;67(1):125-133. [PubMed 19070758]Chornenki NLJ, Um KJ, Mendoza PA, et al. Risk of venous and arterial thrombosis in non-surgical patients receiving systemic tranexamic acid: a systematic review and meta-analysis. Thromb Res. 2019;179:81-86. doi:10.1016/j.thromres.2019.05.003 [PubMed 31100632]Chwajol M, Starke RM, Kim GH, Mayer SA, Connolly ES. Antifibrinolytic therapy to prevent early rebleeding after subarachnoid hemorrhage. Neurocrit Care. 2008;8(3):418-426. doi:10.1007/s12028-008-9088-5 [PubMed 18386187]Colwell C. Initial management of moderate to severe hemorrhage in the adult trauma patient. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 20, 2021.Connolly ES Jr, Rabinstein AA, Carhuapoma JR, et al; American Heart Association Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Clinical Cardiology. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012;43(6):1711-1737. doi:10.1161/STR.0b013e3182587839 [PubMed 22556195]Couture P, Lebon JS, Laliberté É, et al. Low-dose versus high-dose tranexamic acid reduces the risk of nonischemic seizures after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2017;31(5):1611-1617. doi:10.1053/j.jvca.2017.04.026 [PubMed 28803773]Craig T, Aygören-Pürsün E, Bork K, et al. WAO guideline for the management of hereditary angioedema. World Allergy Organ J. 2012;5(12):182-199. doi:10.1097/WOX.0b013e318279affa [PubMed 23282420]CRASH-2 Trial Collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376(9734):23-32. doi:10.1016/S0140-6736(10)60835-5 [PubMed 20554319]CRASH-2 Trial Collaborators. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. 2011;377(9771):1096-1101, 1101.e1-e2. doi:10.1016/S0140-6736(11)60278-X [PubMed 21439633]CRASH-3 Trial Collaborators. Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial [published correction appears in Lancet. 2019;394(10210):1712]. Lancet. 2019;394(10210):1713-1723. doi:10.1016/S0140-6736(19)32233-0 [PubMed 31623894]Cyklokapron (tranexamic acid) [prescribing information]. New York, NY: Pfizer Injectables; March 2021.Cyklokapron (tranexamic acid) [product monograph]. Kirkland, Quebec, Canada: Pfizer Canada Inc; November 2021.Dadure C, Sauter M, Bringuier S, et al. Intraoperative Tranexamic Acid Reduces Blood Transfusion in Children Undergoing Craniosynostosis Surgery: A Randomized Double-Blind Study. Anesthesiology. 2011;114(4):856-861. [PubMed 21358317]Dastrup A, Pottegård A, Hallas J, Overgaard S. Perioperative tranexamic acid treatment and risk of cardiovascular events or death after total hip arthroplasty: a population-based cohort study from National Danish Databases. J Bone Joint Surg Am. 2018;100(20):1742-1749. doi:10.2106/JBJS.17.01518 [PubMed 30334884]Davies D, Howell DA. Tranexamic acid and arterial thrombosis. Lancet. 1977;1(8001):49. doi:10.1016/s0140-6736(77)91690-7 [PubMed 63691]de Guzman R, Polykratis IA, Sondeen JL, Darlington DN, Cap AP, Dubick MA. Stability of tranexamic acid after 12-week storage at temperatures from -20°c to 50°c. Prehosp Emerg Care. 2013;17(3):394-400. doi:10.3109/10903127.2013.792891 [PubMed 23734991]Devereaux PJ, Marcucci M, Painter TW, et al; POISE-3 Investigators. Tranexamic acid in patients undergoing noncardiac surgery. N Engl J Med. 2022;386(21):1986-1997. doi:10.1056/NEJMoa2201171 [PubMed 35363452]Diamond JP, Chandna A, Williams C, Easty DL, Scully C, Eveson J, Richards A. Tranexamic acid-associated ligneous conjunctivitis with gingival and peritoneal lesions. Br J Ophthalmol. 1991;75(12):753-754. doi:10.1136/bjo.75.12.753 [PubMed 1768670]Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2)(suppl):e326S-e350S. doi:10.1378/chest.11-2298 [PubMed 22315266]Dowd NP, Karski JM, Cheng DC, et al. Pharmaco*kinetics of tranexamic acid during cardiopulmonary bypass. Anesthesiology. 2002;97(2):390-399. [PubMed 12151929]Ducloy-Bouthors AS, Jude B, Duhamel A, et al; EXADELI Study Group. High-dose tranexamic acid reduces blood loss in postpartum haemorrhage. Crit Care. 2011;15(2):R117. doi:10.1186/cc10143 [PubMed 21496253]Eaton MP. Antifibrinolytic Therapy in Surgery for Congenital Heart Disease. Anesth Analg. 2008;106(4):1087-1100. [PubMed 18349177]El Hanache H, Verdaguer M, Collin L, et al. Two cases of anaphylaxis to tranexamic acid confirmed by drug provocation test: what about skin tests? J Investig Allergol Clin Immunol. 2021;31(4):351-353. doi:10.18176/jiaci.0651 [PubMed 33136003]Elwatidy S, Jamjoom Z, Elgamal E, et al. Efficacy and Safety of Prophylactic Large Dose of Tranexamic Acid in Spine Surgery: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study. Spine. 2008;33(24):2577-2580. [PubMed 19011538]Erens GA, Walter B, Crowley M. Total hip arthroplasty. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 24, 2022.Farkas H, Martinez-Saguer I, Bork K, et al. International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency. Allergy. 2017;72(2):300‐313. [PubMed 27503784]Farkas H, Varga L, Széplaki G, et al. Management of Hereditary Angioedema in Pediatric Patients. Pediatrics, 2007;120(3):e713-e722. [PubMed 17724112]Faughnan ME, Mager JJ, Hetts SW, et al. Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia. Ann Intern Med. 2020;173(12):989-1001. doi:10.7326/M20-1443 [PubMed 32894695]Fergusson DA, Hébert PC, Mazer CD, et al; BART Investigators. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med. 2008;358(22):2319-2331. doi:10.1056/NEJMoa0802395 [PubMed 18480196]Ferrari FA, Garzon S, Raffaelli R, et al. Tranexamic acid for the prevention and the treatment of primary postpartum haemorrhage: a systematic review. J Obstet Gynaecol. Published online January 7, 2022. doi:10.1080/01443615.2021.2013784 [PubMed 34996342]Ferraris VA, Brown JR Despotis GJ, et al. 2011 Update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists Blood Conservation Clinical Practice Guidelines. Ann Thorac Surg. 2011;91(3):944-982. [PubMed 21353044]Fillingham YA, Ramkumar DB, Jevsevar DS, et al. The safety of tranexamic acid in total joint arthroplasty: a direct meta-analysis. J Arthroplasty. 2018a;33(10):3070-3082.e1. doi:10.1016/j.arth.2018.03.031 [PubMed 29699826]Fillingham YA, Ramkumar DB, Jevsevar DS, et al. Tranexamic acid use in total joint arthroplasty: the clinical practice guidelines endorsed by the American Association of Hip and Knee Surgeons, American Society of Regional Anesthesia and Pain Medicine, American Academy of Orthopaedic Surgeons, Hip Society, and Knee Society. J Arthroplasty. 2018b;33(10):3065-3069. doi:10.1016/j.arth.2018.08.002 [PubMed 30146350]Franchini M, Mengoli C, Marietta M, et al. Safety of intravenous tranexamic acid in patients undergoing majororthopaedic surgery: a meta-analysis of randomised controlled trials. Blood Transfus. 2018;16(1):36-43. doi:10.2450//2017.0219-17 [PubMed 29337665]Frontera JA, Lewin JJ 3rd, Rabinstein AA, et al. Guideline for reversal of antithrombotics in intracranial hemorrhage: a statement for healthcare professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care. 2016;24(1):6-46. doi:10.1007/s12028-015-0222-x [PubMed 26714677]Furtmüller R, Schlag MG, Berger M, et al. Tranexamic acid, a widely used antifibrinolytic agent, causes convulsions by a gamma-aminobutyric acid(A) receptor antagonistic effect. J Pharmacol Exp Ther. 2002;301(1):168-173. doi:10.1124/jpet.301.1.168 [PubMed 11907171]Gaillard S, Dupuis-Girod S, Boutitie F, et al; ATERO Study Group. Tranexamic acid for epistaxis in hereditary hemorrhagic telangiectasia patients: a European cross-over controlled trial in a rare disease. J Thromb Haemost. 2014;12(9):1494-1502. doi:10.1111/jth.12654 [PubMed 25040799]Galvagno S, McCunn M. Anesthesia for adult trauma patients. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 4, 2019.Gaspar R, Brenner B, Ardekian L, Peled M, Laufer D. Use of tranexamic acid mouthwash to prevent postoperative bleeding in oral surgery patients on oral anticoagulant medication. Quintessence Int. 1997;28(6):375-379. [PubMed 9477900]Geisthoff UW, Seyfert UT, Kübler M, Bieg B, Plinkert PK, König J. Treatment of epistaxis in hereditary hemorrhagic telangiectasia with tranexamic acid - a double-blind placebo-controlled cross-over phase IIIB study. Thromb Res. 2014;134(3):565-571. doi:10.1016/j.thromres.2014.06.012 [PubMed 25005464]Gerstein NS, Brierley JK, Culling MD. Left ventricle thrombus after tranexamic acid for spine surgery in an HIV-positive patient. Spine J. 2016;16(2):e77-82. doi:10.1016/j.spinee.2015.10.039 [PubMed 26523960]Gertler R, Gruber M, Grassin-Delyle S, et al. Pharmaco*kinetics of tranexamic acid in neonates and infants undergoing cardiac surgery. Br J Clin Pharmacol. 2017;83(8):1745‐1757. [PubMed 28245519]Gharaibeh A, Savage HI, Scherer RW, Goldberg MF, Lindsley K. Medical interventions for traumatic hyphema. Cochrane Database Syst Rev. 2019;1(1):CD005431. [PubMed 30640411]Gilad O, Merlob P, Stahl B, et al. Outcome following tranexamic acid exposure during breastfeeding. Breastfeed Med. 2014;9(8):407-410. doi: 10.1089/bfm.2014.0027. [PubMed 25025926]Gompels MM, Lock RJ, Abinun M, et al. C1 inhibitor deficiency: consensus document. Clin Exp Immunol. 2005;139(3):379-394. doi:10.1111/j.1365-2249.2005.02726.x [PubMed 15730382]González-Quevedo T, Larco JI, Marcos C, et al. Management of pregnancy and delivery in patients with hereditary angioedema due to C1 inhibitor deficiency. J Investig Allergol Clin Immunol. 2016;26(3):161-167. doi:10.18176/jiaci.0037 [PubMed 27326983]Goobie SM, Faraoni D. Tranexamic acid and perioperative bleeding in children: what do we still need to know? Curr Opin Anaesthesiol. 2019;32(3):343‐352. [PubMed 30893114]Goobie SM, Meier PM, Pereira LM, et al. Efficacy of Tranexamic Acid in Pediatric Craniosynostosis Surgery: A Double-Blind, Placebo-Controlled Trial. Anesthesiology. 2011;114(4):862-871. [PubMed 21364458]Graham EM, Atz AM, Gillis J, et al. Differential effects of aprotinin and tranexamic acid on outcomes and cytokine profiles in neonates undergoing cardiac surgery. J Thorac Cardiovasc Surg. 2012;143(5):1069-1076. [PubMed 22075061]Grant JA, Howard J, Luntley J, et al. Perioperative Blood Transfusion Requirements in Pediatric Scoliosis Surgery: The Efficacy of Tranexamic Acid. J Pediatr Orthop. 2009;29(3):300-304. [PubMed 19305284]Grassin-Delyle S, Couturier R, Abe E, Alvarez JC, Devillier P, Urien S. A practical tranexamic acid dosing scheme based on population pharmaco*kinetics in children undergoing cardiac surgery. Anesthesiology. 2013;118(4):853-862. doi:10.1097/ALN.0b013e318283c83a [PubMed 23343649]Gravlee GP, Spiess B. Pharmacologic prophylaxis for post-Cardiopulmonary bypass bleeding. In: Cardiopulmonary Bypass: Principles and Practice. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008:522-542.Gerstein NS, Brierley JK, Culling MD. Left ventricle thrombus after tranexamic acid for spine surgery in an HIV-positive patient. Spine J. 2016;16(2):e77-82. doi:10.1016/j.spinee.2015.10.039 [PubMed 26523960]Hajmurad OS, Choxi AA, Zahid Z, Dudaryk R. Aortoiliac thrombosis following tranexamic acid administration during urgent cesarean hysterectomy: a case report. A A Case Rep. 2017;9(3):90-93. doi:10.1213/XAA.0000000000000535 [PubMed 28459723]HALT-IT Trial Collaborators. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. Lancet. 2020;395(10241):1927-1936. doi:10.1016/S0140-6736(20)30848-5 [PubMed 32563378]Hillis LD, Smith PK, Anderson JL, et al. 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;124(23):2610-2642. [PubMed 22064600]Hillman J, Fridriksson S, Nilsson O, Yu Z, Saveland H, Jakobsson KE. Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study. J Neurosurg. 2002;97(4):771-778. doi:10.3171/jns.2002.97.4.0771 [PubMed 12405362]Hoots WK, Shapiro AD. Treatment of bleeding and perioperative management in hemophilia A and B. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 23, 2021.Hulde N, Zittermann A, Deutsch MA, von Dossow V, Gummert JF, Koster A. Associations of preoperative stroke and tranexamic acid administration with convulsive seizures in valvular open-heart surgery. J Anesth. 2021;35(3):451-454. doi:10.1007/s00540-021-02924-w [PubMed 33822280]Hulde N, Zittermann A, Deutsch MA, von Dossow V, Gummert JF, Koster A. Tranexamic acid and convulsive seizures after off-pump coronary artery bypass surgery: the role of renal insufficiency. Interact Cardiovasc Thorac Surg. 2019;29(6):852-854. doi:10.1093/icvts/ivz188 [PubMed 31408168]Ijaopo EO, Ijaopo RO, Adjei S. Bilateral pulmonary embolism while receiving tranexamic acid: a case report. J Med Case Rep. 2020;14(1):212. doi:10.1186/s13256-020-02545-z [PubMed 33158458]Imbesi S, Nettis E, Minciullo PL, et al. Hypersensitivity to tranexamic acid: a wide spectrum of adverse reactions. Pharm World Sci. 2010;32(4):416-419. doi:10.1007/s11096-010-9415-8 [PubMed 20632108]Jerath A, Yang QJ, Pang KS, et al. Tranexamic acid dosing for cardiac surgical patients with chronic renal dysfunction: a new dosing regimen. Anesth Analg. 2018;127(6):1323-1332. doi:10.1213/ANE.0000000000002724 [PubMed 29309319]Johnson DJ, Johnson CC, Goobie SM, et al. High-dose versus low-dose tranexamic acid to reduce transfusion requirements in pediatric scoliosis surgery. J Pediatr Orthop. 2017;37(8):e552‐e557. [PubMed 29120963]Johnston LR, Rodriguez CJ, Elster EA, Bradley MJ. Evaluation of military use of tranexamic acid and associated thromboembolic events. JAMA Surg. 2018;153(2):169-175. doi:10.1001/jamasurg.2017.3821 [PubMed 29071337]Kaunitz AM. Abnormal uterine bleeding in nonpregnant reproductive-age patients: management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 29, 2022.Kaku Y, Ito T, Kudo K, Kido-Nakahara M, Nakahara T, Moroi Y, Furue M. Generalized fixed drug eruption induced by tranexamic acid. Eur J Dermatol. 2014;24(3):408-409. doi:10.1684/ejd.2014.2354 [PubMed 24876162]Keijzer R, Wilschut DE, Houmes RJ, et al. Congenital diaphragmatic hernia: to repair on or off extracorporeal membrane oxygenation? J Pediatr Surg. 2012;47(4):631-636. [PubMed 22498373]Kim TK, Chang CB, Kang YG, et al. Clinical value of tranexamic acid in unilateral and simultaneous bilateral TKAs under a contemporary blood-saving protocol: a randomized controlled trial. Knee Surg Sports Traumatol Arthrosc. 2014;22(8):1870-1878. doi:10.1007/s00167-013-2492-1 [PubMed 23592025]Kim YH, Park JW, Kim JS. Chemical thromboprophylaxis is not necessary to reduce risk of thromboembolism with tranexamic acid after total hip arthroplasty. J Arthroplasty. 2017;32(2):641-644. doi:10.1016/j.arth.2016.07.048 [PubMed 27614816]Kiser AS, Cooper GL, Napier JD, Howington GT. Color vision disturbances secondary to oral tranexamic acid. J Am Coll Emerg Physicians Open. 2021;2(3):e12456. doi:10.1002/emp2.12456 [PubMed 34095897]Kitamura H, Matsui I, Itoh N, et al. Tranexamic acid-induced visual impairment in a hemodialysis patient. Clin Exp Nephrol. 2003;7(4):311-4. doi:10.1007/s10157-003-0254-y [PubMed 14712363]Ko BS, Cho KJ, Kim YT, Park JW, Kim NC. Does tranexamic acid increase the incidence of thromboembolism after spinal fusion surgery? Clin Spine Surg. 2020;33(2):E71-E75. doi:10.1097/BSD.0000000000000860 [PubMed 31385850]Ko DH, Kim TH, Kim JW, et al. Tranexamic acid-induced acute renal cortical necrosis in post-endoscopic papillectomy bleeding. Clin Endosc. 2017;50(6):609-613. doi:10.5946/ce.2017.021 [PubMed 28793394]Kratzer S, Irl H, Mattusch C, et al. Tranexamic acid impairs γ-aminobutyric acid receptor type A-mediated synaptic transmission in the murine amygdala: a potential mechanism for drug-induced seizures? Anesthesiology. 2014;120(3):639-69. doi:10.1097/ALN.0000000000000103 [PubMed 24335749]Kurnik NM, Pflibsen LR, Bristol RE, Singh DJ. Tranexamic acid reduces blood loss in craniosynostosis surgery. J Craniofac Surg. 2017;28(5):1325‐1329. [PubMed 28582303]Lam MS. Extemporaneous compounding of oral liquid dosage formulations and alternative drug delivery methods for anticancer drugs. Pharmacotherapy. 2011;31(2):164-192. doi:10.1592/phco.31.2.164 [PubMed 21275495]Lecker I, Wang DS, Romaschin AD, Peterson M, Mazer CD, Orser BA. Tranexamic acid concentrations associated with human seizures inhibit glycine receptors. J Clin Invest. 2012;122(12):4654-4666. doi:10.1172/JCI63375 [PubMed 23187124]Lecker I, Wang DS, Whissell PD, Avramescu S, Mazer CD, Orser BA. Tranexamic acid-associated seizures: causes and treatment. Ann Neurol. 2016;79(1):18-26. doi:10.1002/ana.24558 [PubMed 26580862]Leverett GD, Marriott A. Intravenous tranexamic acid and thromboembolic events in hip fracture surgery: a systematic review and meta-analysis. Orthop Traumatol Surg Res. 2022 May 25:103337. doi:10.1016/j.otsr.2022.103337 [PubMed 35643364]Levin E, Wu J, Devine DV, et al. Hemostatic Parameters and Platelet Activation Marker Expression in Cyanotic and Acyanotic Pediatric Patients Undergoing Cardiac Surgery in the Presence of Tranexamic Acid. Thromb Haemost. 2000;83(1):54-59. [PubMed 10669155]Levy JH, Freiberger DJ, Roback J. Hereditary angioedema: current and emerging treatment options. Anesth Analg. 2010;110(5):1271-1280. doi:10.1213/ANE.0b013e3181d7ac98 [PubMed 20418292]Levy JH, Koster A, Quinones QJ, Milling TJ, Key NS. Antifibrinolytic therapy and perioperative considerations. Anesthesiology. 2018;128(3):657-670. doi:10.1097/ALN.0000000000001997 [PubMed 29200009]Lin Z, Xiaoyi Z. Tranexamic acid-associated seizures: a meta-analysis. Seizure. 2016;36:70-73. doi:10.1016/j.seizure.2016.02.011 [PubMed 26967164]Li PH, Trigg C, Rutkowski R, Rutkowski K. Anaphylaxis to tranexamic acid-a rare reaction to a common drug. J Allergy Clin Immunol Pract. 2017;5(3):839-841. doi:10.1016/j.jaip.2016.12.014 [PubMed 28117269]Li S, Ahmadzia HK, Guo D, et al. Population pharmaco*kinetics and pharmacodynamics of tranexamic acid in women undergoing caesarean delivery. Br J Clin Pharmacol. 2021;87(9):3531-3541. doi:10.1111/bcp.14767 [PubMed 33576009]Lu VM, Ho YT, Nambiar M, Mobbs RJ, Phan K. The perioperative efficacy and safety of antifibrinolytics in adult spinal fusion surgery: a systematic review and meta-analysis. Spine (Phila Pa 1976). 2018;43(16):E949-E958. doi:10.1097/BRS.0000000000002580 [PubMed 30063223]Lysteda (tranexamic acid) (prescribing information). Parsippany, NJ: Ferring Pharmaceuticals Inc; December 2020.MacGillivray RG, Tarabichi SB, Hawari MF, Raoof NT. Tranexamic acid to reduce blood loss after bilateral total knee arthroplasty: a prospective, randomized double blind study. J Arthroplasty. 2011;26(1):24-28. doi:10.1016/j.arth.2009.11.013 [PubMed 20171048]Machado AM, Pires RM, Martins RO, et al. Pregnancy and postpartum in hereditary angioedema with C1 inhibitor deficit in women who have no access to therapy. J Investig Allergol Clin Immunol. 2017;27(5):322-323. doi:10.18176/jiaci.0175 [PubMed 29057741]Madsen RV, Nielsen CS, Kallemose T, Husted H, Troelsen A. Low risk of thromboembolic events after routine administration of tranexamic acid in hip and knee arthroplasty. J Arthroplasty. 2017;32(4):1298-1303. doi:10.1016/j.arth.2016.10.015 [PubMed 27843042]Maniar RN, Kumar G, Singhi T, Nayak RM, Maniar PR. Most effective regimen of tranexamic acid in knee arthroplasty: a prospective randomized controlled study in 240 patients. Clin Orthop Relat Res. 2012;470(9):2605-2612. doi:10.1007/s11999-012-2310-y [PubMed 22419350]Manji RA, Grocott HP, Leake J, et al. Seizures following cardiac surgery: the impact of tranexamic acid and other risk factors. Can J Anaesth. 2012;59(1):6-13. doi:10.1007/s12630-011-9618-z [PubMed 22065333]Martin DT, Gries H, Esmonde N, et al. Implementation of a tranexamic acid protocol to reduce blood loss during cranial vault remodeling for craniosynostosis. J Craniofac Surg. 2016;27(6):1527‐1531. [PubMed 27557459]Martin GM, Roe J. Total knee arthroplasty. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 7, 2020.Maurer M, Magerl M, Ansotegui I, et al. The international WAO/EAACI guideline for the management of hereditary angioedema-the 2017 revision and update. Allergy. 2018;73(8):1575-1596. doi:10.1111/all.13384 [PubMed 29318628]Maurer M, Magerl M, Betschel S, et al. The international WAO/EAACI guideline for the management of hereditary angioedema-the 2021 revision and update. Allergy. Published online January 10, 2022. doi:10.1111/all.15214 [PubMed 35006617]McCluskey SV, Sztajnkrycer MD, Jenkins DA, Zietlow SP, Berns KS, Park MS. Stability of tranexamic acid in 0.9% sodium chloride, stored in type 1 glass vials and ethylene/propylene copolymer plastic containers. Int J Pharm Compd. 2014;18(5):432-437. [PubMed 25577894]Meaidi A, Mørch L, Torp-Pedersen C, Lidegaard O. Oral tranexamic acid and thrombosis risk in women. EClinicalMedicine. 2021;35:100882. doi:10.1016/j.eclinm.2021.100882 [PubMed 34124632]Milingos DS, Madhuvrata P, Dean J, et al. Hereditary angioedema and pregnancy: successful management of recurrent and frequent attacks of angioedema with C1-inhibitor concentrate, danazol and tranexamic acid - a case report. Obstet Med. 2009;2(3):123-125. doi:10.1258/om.2009.090003 [PubMed 27582827]Mindel JS. Problems in the use of tranexamic acid by ophthalmologists. Arch Ophthalmol. 1989;107(4):486-487. doi:10.1001/archopht.1989.01070010500006 [PubMed 2705908]Montes FR, Pardo DF, Carreño M, Arciniegas C, Dennis RJ, Umaña JP. Risk factors associated with postoperative seizures in patients undergoing cardiac surgery who received tranexamic acid: a case-control study. Ann Card Anaesth. 2012;15(1):6-12. doi:10.4103/0971-9784.91467 [PubMed 22234015]Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg. 2012;147(2):113-119. [PubMed 22006852]Muhunthan K, Balakumar S, Navaratnaraja TS, Premakrishna S, Arulkumaran S. Plasma concentrations of tranexamic acid in postpartum women after oral administration. Obstet Gynecol. 2020;135(4):945-948. doi:10.1097/AOG.0000000000003750 [PubMed 32168220]Muñoz M, Stensballe J, Ducloy-Bouthors AS, et al. Patient blood management in obstetrics: prevention and treatment of postpartum haemorrhage. A NATA consensus statement. Blood Transfus. 2019;17(2):112-136. doi:10.2450/2019.0245-18 [PubMed 30865585]Murao S, Nakata H, Roberts I, Yamakawa K. Effect of tranexamic acid on thrombotic events and seizures in bleeding patients: a systematic review and meta-analysis. Crit Care. 2021;25(1):380. doi:10.1186/s13054-021-03799-9 [PubMed 34724964]Murdaca G, Greco M, Vassallo C, Gangemi S. Tranexamic acid adverse reactions: a brief summary for internists and emergency doctors. Clin Mol Allergy. 2020;18:16. doi:10.1186/s12948-020-00131-8 [PubMed 32908455]Murkin JM, Falter F, Granton J, et al. High-Dose Tranexamic Acid is Associated With Nonischemic Clinical Seizures in Cardiac Surgical Patients. Anesth Anal. 2010;110(2):350-353. [PubMed 19996135]Myers SP, Kutcher ME, Rosengart MR, et al. Tranexamic acid administration is associated with an increased risk of posttraumatic venous thromboembolism. J Trauma Acute Care Surg. 2019;86(1):20-27. doi:10.1097/TA.0000000000002061 [PubMed 30239375]Myles PS, Smith JA, Forbes A, et al; ATACAS Investigators of the ANZCA Clinical Trials Network. Tranexamic acid in patients undergoing coronary-artery surgery. N Engl J Med. 2017;376(2):136-148. doi:10.1056/NEJMoa1606424 [PubMed 27774838]National Alert Network (NAN). NAN Alert. Dangerous wrong-route errors with tranexamic acid. https://www.ismp.org/sites/default/files/attachments/2020-09/NAN%20Alert%2020200909.pdf. Published September 9, 2020. Accessed September 14, 2020.National Institute for Health and Care Excellence. Drug allergy: diagnosis and management. Published September 3, 2014. Accessed October 23, 2020. https://www.nice.org.uk/guidance/cg183Neilipovitz DT, Murto K, Hall L, et al. A Randomized Trial of Tranexamic Acid to Reduce Blood Transfusion for Scoliosis Surgery. Anesth Analg. 2001;93(1):82-87. [PubMed 11429344]Nishida T, Kinosh*ta T, Yamakawa K. Tranexamic acid and trauma-induced coagulopathy. J Intensive Care. 2017;5:5. doi:10.1186/s40560-016-0201-0 [PubMed 28729903]Novikova N, Hofmeyr GJ, Cluver C. Tranexamic acid for preventing postpartum haemorrhage. Cochrane Database Syst Rev. 2015;(6):CD007872. doi:10.1002/14651858.CD007872.pub3 [PubMed 26079202]Nuttall GA, Gutierrez MC, Dewey JD, et al. A preliminary study of a new tranexamic acid dosing schedule for cardiac surgery. J Cardiothorac Vasc Anesth. 2008;22(2):230-235. doi:10.1053/j.jvca.2007.12.016 [PubMed 18375325]O'Neil ER, Schmees LR, Resendiz K, Justino H, Anders MM. Inhaled tranexamic acid as a novel treatment for pulmonary hemorrhage in critically ill pediatric patients: an observational study. Crit Care Explor. 2020;2(1):e0075. [PubMed 32166295]Pabinger I, Fries D, Schöchl H, Streif W, Toller W. Tranexamic acid for treatment and prophylaxis of bleeding and hyperfibrinolysis. Wien Klin Wochenschr. 2017;129(9-10):303-316. doi:10.1007/s00508-017-1194-y [PubMed 28432428]Parsons MR, Merritt DR, Ramsay RC. Retinal artery occlusion associated with tranexamic acid therapy. Am J Ophthalmol. 1988;105(6):688-689. doi:10.1016/0002-9394(88)90069-4 [PubMed 3163896]Patatanian E, Fugate SE. Hemostatic mouthwashes in anticoagulated patients undergoing dental extraction. Ann Pharmacother. 2006;40(12):2205-2210. doi:10.1345/aph.1H295 [PubMed 17090725]Patel S, Robertson B, McConachie I. Catastrophic drug errors involving tranexamic acid administered during spinal anaesthesia. Anaesthesia. 2019;74(7):904-914. doi:10.1111/anae.14662 [PubMed 30985928]Pavord S, Myers B. Bleeding and thrombotic complications of kidney disease. Blood Rev. 2011;25(6):271-278. doi:10.1016/j.blre.2011.07.001 [PubMed 21872374]Pavord S, Rayment R, Madan B, et al; Royal College of Obstetricians and Gynaecologists. Management of inherited bleeding disorders in pregnancy. Green-top Guideline No. 71. BJOG. 2017;124(8):e193-e263. doi:10.1111/1471-0528.14592 [PubMed 28447403]Pennington Z, Ehresman J, Schilling A, et al. Influence of tranexamic acid use on venous thromboembolism risk in patients undergoing surgery for spine tumors. J Neurosurg Spine. 2021:1-11. doi:10.3171/2021.1.SPINE201935 [PubMed 34388705]Porter SB, Spaulding AC, Duncan CM, Wilke BK, Pagnano MW, Abdel MP. Tranexamic acid was not associated with increased complications in high-risk patients with intertrochanteric fracture. J Bone Joint Surg Am. 2022;104(13):1138-1147. doi:10.2106/JBJS.21.01389 [PubMed 35775092]Post R, Germans MR, Tjerkstra MA, et al; ULTRA Investigators. Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial. Lancet. 2021;397(10269):112-118. doi:10.1016/S0140-6736(20)32518-6 [PubMed 33357465]Powers WJ, Rabinstein AA, Ackerson T, et al; American Heart Association Stroke Council. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46-e110. doi:10.1161/STR.0000000000000158 [PubMed 29367334]Pretel Irazabal M, Marques Martin L, Aguado Gil L, Idoate Gastearena MA. Tranexamic acid-induced toxic epidermal necrolysis. Ann Pharmacother. 2013;47(3):e16. doi:10.1345/aph.1R637 [PubMed 23447480]Rahmani B, Jahadi HR. Comparison of Tranexamic Acid and Prednisolone in the Treatment of Traumatic Hyphema. Ophthalmology. 1999;106(2):375-379. [PubMed 9951493]Rajajee V. Management of acute moderate and severe traumatic brain injury. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 12, 2020.Refer to manufacturer labeling.Reid RW, Zimmerman AA, Laussen PC, et al. The Efficacy of Tranexamic Acid Versus Placebo in Decreasing Blood Loss in Pediatric Patients Undergoing Repeat Cardiac Surgery. Anesth Analg. 1997;84(5):990-996. [PubMed 9141920]Roos Y. Antifibrinolytic treatment in subarachnoid hemorrhage: a randomized placebo-controlled trial. STAR Study Group. Neurology. 2000;54(1):77-82. [PubMed 10636129]Roos YB, Rinkel GJ, Vermeulen M, Algra A, van Gijn J. Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2003;(2):CD001245. doi:10.1002/14651858.CD001245 [PubMed 12804399]Royal College of Paediatrics and Child Health. Evidence statement: Major trauma and the use of tranexamic acid in children. November 2012. https://www.rcem.ac.uk/docs/External%20Guidance/10k.%20Major%20trauma%20and%20the%20use%20of%20tranexamic%20acid%20in%20children%20Evidence%20statement%20(RCPCH,%20Nov%202012).pdf.Saccone G, Della Corte L, D'Alessandro P, et al. Prophylactic use of tranexamic acid after vagin*l delivery reduces the risk of primary postpartum hemorrhage. J Matern Fetal Neonatal Med. 2019:1-9. doi:10.1080/14767058.2019.1571576 [PubMed 30704334]Schindler E, Photiadis J, Sinzobahamvya N, Döres A, Asfour B, Hraska V. Tranexamic acid: an alternative to aprotinin as antifibrinolytic therapy in pediatric congenital heart surgery. Eur J Cardiothorac Surg. 2011;39(4):495-499. [PubMed 20832330]Schrijvers R, Gilissen L, Chiriac AM, Demoly P. Pathogenesis and diagnosis of delayed-type drug hypersensitivity reactions, from bedside to bench and back. Clin Transl Allergy. 2015;5:31. doi: 10.1186/s13601-015-0073-8 [PubMed 26339470]Segrelles Calvo G, De Granda-Orive I, López Padilla D. Inhaled tranexamic acid as an alternative for hemoptysis treatment. Chest. 2016;149(2):604. doi:10.1016/j.chest.2015.10.016 [PubMed 26867844]Sentilhes L, Sénat MV, Le Lous M, et al; Groupe de Recherche en Obstétrique et Gynécologie. Tranexamic acid for the prevention of blood loss after cesarean delivery. N Engl J Med. 2021;384(17):1623-1634. doi:10.1056/NEJMoa2028788 [PubMed 33913639]Sentilhes L, Winer N, Azria E, et al; Groupe de Recherche en Obstétrique et Gynécologie. Tranexamic acid for the prevention of blood loss after vagin*l delivery. N Engl J Med. 2018;379(8):731-742. doi:10.1056/NEJMoa1800942. [PubMed 30134136]Sethna NF, Zurakowski D, Brustowicz RM, et al. Tranexamic Acid Reduces Intraoperative Blood Loss in Pediatric Patients Undergoing Scoliosis Surgery. Anesthesiology. 2005;102(4):727-732. [PubMed 15791100]Shakur H, Elbourne D, Gülmezoglu M, et al. The WOMAN Trial (World Maternal Antifibrinolytic Trial): tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind placebo controlled trial. Trials. 2010;11:40. doi:10.1186/1745-6215-11-40 [PubMed 20398351]Shapiro F, Zurakowski D, Sethna NF. Tranexamic Acid Diminishes Intraoperative Blood Loss and Transfusion in Spinal Fusions for duch*enne Muscular Dystrophy Scoliosis. Spine (Phila Pa 1976). 2007;32(20):2278-2283. [PubMed 17873823]Sharma V, Katznelson R, Jerath A, et al. The association between tranexamic acid and convulsive seizures after cardiac surgery: a multivariate analysis in 11 529 patients. Anaesthesia. 2014;69(2):124-130. doi:10.1111/anae.12516 [PubMed 24588023]Shi J, Zhou C, Pan W, et al. Effect of high- vs low-dose tranexamic acid infusion on need for red blood cell transfusion and adverse events in patients undergoing cardiac surgery: the OPTIMAL Randomized Clinical Trial. JAMA. 2022;328(4):336-347. doi:10.1001/jama.2022.10725 [PubMed 35881121]Shimizu K, Toda Y, Iwasaki T, et al. Effect of tranexamic acid on blood loss in pediatric cardiac surgery: a randomized trial. J Anesth. 2011;25(6):823‐830. [PubMed 21947753]Sigaut S, Tremey B, Ouattara A, et al. Comparison of two doses of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass. Anesthesiology. 2014;120(3):590-600. doi:10.1097/ALN.0b013e3182a443e8 [PubMed 23903022]Sindet-Pedersen S. Distribution of tranexamic acid to plasma and saliva after oral administration and mouth rinsing: a pharmaco*kinetic study. J Clin Pharmacol. 1987;27(12):1005-1008. doi:10.1002/j.1552-4604.1987.tb05605.x [PubMed 3437064]Simonazzi G, Bisulli M, Saccone G, Moro E, Marshall A, Berghella V. Tranexamic acid for preventing postpartum blood loss after cesarean delivery: a systematic review and meta-analysis of randomized controlled trials. Acta Obstet Gynecol Scand. 2016;95(1):28-37. doi:10.1111/aogs.12798 [PubMed 26698831]Smetzer J, Cohen M, Shastay A, Jenkins R, Litman RS, eds. Dangerous wrong-route errors with tranexamic acid-a major cause for concern. ISMP Medication Safety Alert! Acute Care Edition. 2019;24(10):2-4.Song Y, Izumi N, Potts LB, Yoshida A. Tranexamic acid-induced ligneous conjunctivitis with renal failure showed reversible hypoplasminogenaemia. BMJ Case Rep. 2014;2014:bcr2014204138. doi:10.1136/bcr-2014-204138 [PubMed 24842363]Spinella PC, Bochicchio K, Thomas KA, et al. The risk of thromboembolic events with early intravenous 2- and 4-g bolus dosing of tranexamic acid compared to placebo in patients with severe traumatic bleeding: a secondary analysis of a randomized, double-blind, placebo-controlled, single-center trial. Transfusion. 2022;62 (Suppl 1):S139-S150. doi:10.1111/trf.16962 [PubMed 35765921]Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al; Treatment Guidelines Working Group on behalf of The World Federation of Hemophilia. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1-e47. doi:10.1111/j.1365-2516.2012.02909.x [PubMed 22776238]Starke RM, Connolly ES Jr; Participants in the International Multi-Disciplinary Consensus Conference on the Critical Care Management of Subarachnoid Hemorrhage. Rebleeding after aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2011;15(2):241-246. doi:10.1007/s12028-011-9581-0 [PubMed 21761274]Taeuber I, Weibel S, Herrmann E, et al. Association of intravenous tranexamic acid with thromboembolic events and mortality: a systematic review, meta-analysis, and meta-regression. JAMA Surg. 2021;156(6):e210884. doi:10.1001/jamasurg.2021.0884 [PubMed 33851983]Tranexamic acid in sodium chloride injection [prescribing information]. Lenoir, NC: Exela Pharma Sciences LLC; July 2020.van der Staak FH, de Haan AF, Geven WB, et al. Surgical Repair of Congenital Diaphragmatic Hernia During Extracorporeal Membrane Oxygenation: Hemorrhagic Complications and the Effect of Tranexamic Acid. J Ped Surg. 1997;32(4):594-599. [PubMed 9126762]van Galen KP, Engelen ET, Mauser-Bunschoten EP, van Es RJ, Schutgens RE. Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or von Willebrand disease undergoing minor oral surgery or dental extractions. Cochrane Database Syst Rev. 2019;4:CD011385. doi:10.1002/14651858.CD011385.pub3 [PubMed 31002742]Vangsted P, Nielsen PJ. Tranexamic Acid and Traumatic Hyphaema, A Prospective Study. Acta Ophthalmol (Copenh). 1983;61(3):447-453. [PubMed 6353843]Verma K, Errico TJ, Vaz KM, et al. A prospective, Randomized, Double-Blinded Single-Site Control Study Comparing Blood Loss Prevention of Tranexamic Acid (TXA) to Epsilon Aminocaproic Acid (EACA) for Corrective Spinal Surgery. BMC Surg. 2010;10:13. [PubMed 20370916]Verstraete M. Clinical application of inhibitors of fibrinolysis. Drugs. 1985;29(3):236-261. [PubMed 2580684]Wand O, Guber E, Guber A, Epstein Shochet G, Israeli-Shani L, sh*trit D. Inhaled tranexamic acid for hemoptysis treatment: a randomized controlled trial. Chest. 2018;154(6):1379-1384. doi:10.1016/j.chest.2018.09.026 [PubMed 30321510]Wijetilleka S, Yeo DCM, Sharma B. Central retinal artery occlusion in a 30-year-old woman taking tranexamic acid. BMJ Case Rep. 2017;2017:bcr2016218246. doi:10.1136/bcr-2016-218246 [PubMed 28705840]WOMAN Trial Collaborators. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial [published correction appears in Lancet. 2017;389(10084):2104]. Lancet. 2017;389(10084):2105-2116. doi:10.1016/S0140-6736(17)30638-4 [PubMed 28456509]Wong J, El Beheiry H, Rampersaud YR, et al. Tranexamic acid reduces perioperative blood loss in adult patients having spinal fusion surgery. Anesth Analg. 2008;107(5):1479-1486. doi:10.1213/ane.0b013e3181831e44 [PubMed 18931202]World Health Organization. WHO Recommendation on Tranexamic Acid for the Treatment of Postpartum Haemorrhage. Geneva: World Health Organization; 2017. http://www.who.int/reproductivehealth/publications/tranexamic-acid-pph-treatment/en/. Published 2017. Accessed April 6, 2018.Xia Y, Griffiths BB, Xue Q. Tranexamic acid for postpartum hemorrhage prevention in vagin*l delivery: a meta-analysis. Medicine (Baltimore). 2020;99(3):e18792. doi:10.1097/MD.0000000000018792 [PubMed 32011478]Xiao C, Zhang S, Long N, Yu W, Jiang Y. Is intravenous tranexamic acid effective and safe during hip fracture surgery? An updated meta-analysis of randomized controlled trials. Arch Orthop Trauma Surg. 2019;139(7):893-902. doi:10.1007/s00402-019-03118-6 [PubMed 30637503]Xie Q, Huang CJ, Gu KP, Yao YX. Circulation collapse caused by intracardiac thrombosis associated with tranexamic acid administration: a case report. Medicine (Baltimore). 2021;100(47):e27997. doi:10.1097/MD.0000000000027997 [PubMed 34964796]Yang QJ, Jerath A, Bies RR, Wąsowicz M, Pang KS. Pharmaco*kinetic modeling of tranexamic acid for patients undergoing cardiac surgery with normal renal function and model simulations for patients with renal impairment. Biopharm Drug Dispos. 2015;36(5):294-307. doi:10.1002/bdd.1941 [PubMed 25704361]Yee BE, Wissler RN, Zanghi CN, Feng C, Eaton MP. The effective concentration of tranexamic acid for inhibition of fibrinolysis in neonatal plasma in vitro. Anesth Analg. 2013;117(4):767-772. doi:10.1213/ANE.0b013e3182a22258 [PubMed 24023015]Zaffar N, Ravichakaravarthy T, Faughnan ME, Shehata N. The use of anti-fibrinolytic agents in patients with HHT: a retrospective survey. Ann Hematol. 2015;94(1):145-152. doi:10.1007/s00277-014-2169-y [PubMed 25064693]Zufferey PJ, Miquet M, Quenet S, et al; Tranexamic Acid in Hip-Fracture Surgery (THIF) Study Investigators. Tranexamic acid in hip fracture surgery: a randomized controlled trial. Br J Anaesth. 2010;104(1):23-30. doi:10.1093/bja/aep314 [PubMed 19926634]Zuraw B, Farkas H. Hereditary angioedema (due to C1 inhibitor deficiency): general care and long-term prophylaxis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 11, 2022.Zuraw BL, Bernstein JA, Lang DM, et al. A focused parameter update: hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema. J Allergy Clin Immunol. 2013;131(6):1491‐1493. [PubMed 23726531]Topic 12854 Version 376.0

CloseInsulin glargine (including biosimilars): Drug informationInsulin glargine (including biosimilars): Drug information(For additional information see "Insulin glargine (including biosimilars): Patient drug information" and see "Insulin glargine (including biosimilars): Pediatric drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USBasaglar KwikPen;Basaglar Tempo Pen;Lantus;Lantus SoloStar;Semglee (yfgn);Semglee [DSC];Toujeo Max SoloStar;Toujeo SoloStarBrand Names: CanadaBasaglar;Basaglar KwikPen;Lantus;Lantus SoloStar;Semglee;Toujeo Doublestar;Toujeo SoloStarPharmacologic CategoryInsulin, Long-ActingDosing: AdultNote: Insulin glargine-yfgn (Semglee, generic) has been approved as a biosimilar to Lantus (insulin glargine). Insulin glargine is a basal insulin. Insulin requirements vary between patients; monitor glucose levels frequently and individualize dose.Diabetes mellitus, type 1, treatmentDiabetes mellitus, type 1, treatment:Note: Insulin glargine must be used concomitantly with rapid- or short-acting insulins (ie, multiple daily injection regimen). The total daily doses (TDDs) presented below are expressed as the total units/kg/day of all insulin formulations (basal and prandial) combined.General insulin dosing:Initial TDD: SUBQ: 0.4 to 0.5 units/kg/day in divided doses; conservative initial doses of 0.2 to 0.4 units/kg/day may be considered to avoid hypoglycemia (Ref).Usual TDD maintenance range: SUBQ: 0.4 to 1 units/kg/day in divided doses (Ref).Division of TDD (multiple daily injections):Basal insulin: SUBQ: 40% to 50% of the TDD administered as insulin glargine once daily (Ref). In patients with inadequate basal insulin coverage with once-daily dosing, administration of U-100 (100 units/mL) formulations in 2 divided doses may be beneficial (Ref).Prandial insulin: SUBQ: The remaining portion (ie, 50% to 60%) of the TDD is then divided and administered before, at, or just after mealtimes, depending on the formulation (Ref).Dosage adjustment for glycemic control: SUBQ: Increase or decrease daily dose by 10% to 20% once or twice weekly (eg, every 3 or 7 days) to maintain premeal and bedtime glucose in target range; avoid more frequent dosage adjustment to minimize hypoglycemia risk (Ref).Preoperative dosage adjustment: Dose reductions are applied to the morning and/or evening insulin glargine doses as follows:Evening scheduled dosage adjustment: SUBQ: Reduce insulin glargine dose by 10% to 25% the evening before the procedure; may administer the full dose in patients whose glucose levels are generally elevated (eg, >200 mg/dL) (Ref).Morning scheduled dosage adjustment: SUBQ: Administer one-half to two-thirds of the total morning insulin dose (basal + prandial) as insulin glargine the morning of the procedure (Ref).Diabetes mellitus, type 2, treatmentDiabetes mellitus, type 2, treatment:Note: Preferred in patients with symptomatic hyperglycemia (eg, weight loss, polydipsia, polyuria) or ketonuria; may also be used in patients with severe hyperglycemia (eg, fasting glucose >250 mg/dL, random glucose consistently >300 mg/dL, HbA1c >9%), or if glycemic goals are not met despite adequately titrated metformin with or without other noninsulin agents (Ref). Consider discontinuation or a dose reduction of sulfonylureas and thiazolidinediones when initiating basal insulin therapy (Ref).Initial: SUBQ: 10 units once daily or 0.1 to 0.2 units/kg once daily (Ref). In patients with HbA1c >8%, fasting plasma glucose >250 mg/dL, or insulin resistance, 0.2 to 0.3 units/kg/day is recommended (Ref). Some experts use a minimum of 10 units/day and do not exceed 20 units/day for the initial dose (Ref).Dosage adjustment:For persistently elevated fasting plasma glucose: SUBQ: Increase daily dose by 2 to 4 units or by 10% to 20% every 2 to 3 days to achieve fasting plasma glucose target while avoiding hypoglycemia (Ref).For elevated HbA1c despite achieving fasting plasma glucose target: SUBQ: Encourage lifestyle modifications. Consider adding other medications (eg, a glucagon-like peptide-1 receptor agonist, prandial insulin before the largest meal). In patients taking high doses (eg, >80 units/day) of U-100 (100 units/mL) formulations once daily, an alternative is to switch to a twice-daily regimen by administering the current daily dose in 2 equally divided doses (Ref). In some patients, higher insulin glargine doses (eg, >0.5 units/kg/day) may provide diminishing additional improvements in HbA1c (Ref).For hypoglycemia: SUBQ: For unexplained mild to moderate hypoglycemia, consider decreasing daily dose by 10% to 20% (Ref); for severe hypoglycemia requiring assistance from another person or blood glucose <40 mg/dL, consider decreasing daily dose by 20% to 50% (Ref).Dosage adjustment when adding prandial insulin: SUBQ: In patients whose glucose levels are close to target (eg, HbA1c <8%), consider decreasing the basal insulin daily dose by 4 units or by 10% (Ref).Preoperative dosage adjustment: Dose reductions are applied to the morning and/or evening insulin glargine doses as follows:Evening scheduled dosage adjustment: SUBQ: Reduce insulin glargine dose by 10% to 25% the evening before the procedure; may administer the full dose if preoperative hypoglycemia risk is low (eg, glucose levels generally >200 mg/dL) (Ref).Morning scheduled dosage adjustment: SUBQ: For patients not using prandial insulin, reduce insulin glargine dose by 10% to 25% the morning of the procedure; may administer the full dose if preoperative hypoglycemia risk is low (eg, glucose levels generally >200 mg/dL). For patients using prandial insulin, omit prandial insulin after fasting begins and administer one-half to two-thirds of the total morning insulin dose (basal + prandial) as insulin glargine the morning of the procedure (Ref).Hyperglycemia in hospitalized patientsHyperglycemia in hospitalized patients (off-label use):Note: For use in patients with persistent hyperglycemia (eg, blood glucose ≥140 to 180 mg/dL for >12 to 24 hours) with or without a history of diabetes; patients with type 1 diabetes require basal insulin therapy regardless of glucose levels or nutritional intake. Dose is individualized; use of institution-specific protocols to achieve glycemic targets and minimize hypoglycemia is encouraged (Ref).Initial (insulin glargine 100 units/mL formulations only):Patients not receiving basal insulin prior to hospitalization: SUBQ: 0.1 to 0.3 units/kg administered once daily (Ref). Note: Consider doses at the lower end of this range in patients ≥70 years of age and in those with renal impairment; consider doses at the higher end of this range in patients with glucose levels >200 mg/dL or who are receiving glucocorticoids (Ref).Patients receiving basal insulin prior to hospitalization: SUBQ: Continue the prehospitalization basal insulin dose; an empiric 20% to 50% dose reduction may be considered in patients whose prehospitalization glucose levels were within target range, or in patients with impaired renal function, poor nutritional intake, or admission glucose levels <100 mg/dL; higher doses may be required in patients receiving glucocorticoids (Ref).Patients transitioning from an IV insulin infusion: SUBQ: Refer to institution-specific protocols. In patients whose insulin requirements are known, prior basal insulin regimen may be resumed (Ref). In patients whose insulin requirements are not known, total daily dosage may be estimated as 60% to 80% of the mean IV insulin dosage over the prior 6 hours, or by using weight-based dosing of 0.1 to 0.3 units/kg administered once daily (Ref). Note: Administer initial dose of basal insulin ≥2 to 4 hours before discontinuing IV insulin infusion (Ref).Dosage adjustment: SUBQ: Adjust daily dose by 10% to 20% every 2 to 3 days to achieve glycemic targets (Ref). Consider reducing dosage for glucose levels <100 mg/dL to avoid hypoglycemia; in patients with glucose levels <40 mg/dL, larger dose reductions (eg, by 20% to 40%) may be needed (Ref).Conversion between basal insulin products:Conversion from NPH insulin to insulin glargine:Converting from once-daily NPH insulin to insulin glargine: SUBQ: Initial: May be substituted on an equivalent unit-per-unit basis.Converting from twice-daily NPH insulin to insulin glargine: SUBQ: Initial: Administer 80% of the total daily NPH dose as insulin glargine once daily.Conversion from insulin detemir to insulin glargine:Converting from once-daily insulin detemir to insulin glargine U-300 (300 units/mL): SUBQ: Initial: May be substituted on an equivalent unit-per-unit basis.Converting from once-daily insulin detemir to insulin glargine U-100 (100 units/mL) formulations: SUBQ: Initial: Administer 80% to 90% of the total daily insulin detemir dose as insulin glargine once daily (Ref).Converting from twice-daily insulin detemir to insulin glargine: SUBQ: Initial: Administer 80% to 90% of the total daily insulin detemir dose as insulin glargine once daily (Ref).Conversion between insulin glargine products (Toujeo, Lantus, Basaglar, or insulin glargine-yfgn [Semglee, generic]):Conversion from once-daily Toujeo (300 units/mL) to once-daily Lantus, Basaglar, or insulin glargine-yfgn (Semglee, generic) (100 units/mL): SUBQ: Initial: Administer 80% of the Toujeo dose.Conversion from once-daily Lantus to once-daily Toujeo or once-daily Basaglar: SUBQ: Initial: May be substituted on an equivalent unit-per-unit basis; a higher daily dosage of Toujeo will generally be required to achieve the same level of glycemic control as with Lantus.Conversion between Toujeo SoloStar and Toujeo Max SoloStar (or Toujeo DoubleStar [Canadian product]): SUBQ: Initial: If previous dose was an odd number, the dose should be increased or decreased by 1 unit.Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultThe renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.Altered kidney function:Note: Recommendations are expert opinion derived from Aronoff 2007, Baldwin 2012, Biesenbach 2003, Kulozik 2013, Rahhal 2019, Rajput 2017, and Rashid 2004 (Ref).Initial dosing: SUBQ: When initiating insulin glargine, the following recommendations based on kidney function are suggested:eGFR ≥50 mL/minute/1.73 m2: No dosage adjustment necessary.eGFR >10 to <50 mL/minute/1.73 m2: Administer 75% of the usual starting dose.eGFR ≤10 mL/minute/1.73 m2: Administer 50% of the usual starting dose.Dosage adjustment: SUBQ: Dose adjustments should generally follow the indication-specific recommendations as described in the adult dosing section but titrated more gradually; in patients with eGFR <60 mL/minute/1.73 m2, use with caution and monitor glucose levels frequently.Hemodialysis, intermittent (thrice weekly): Initial dosing: SUBQ: When initiating insulin glargine, administer 50% of the usual starting dose (Ref). Dose adjustments should generally follow the indication-specific recommendations as described in the adult dosing section but titrated more gradually; in patients experiencing hypoglycemia, consider more aggressive dose reductions (eg, by 25% to 40%) depending on severity (Ref).Peritoneal dialysis: Initial dosing: SUBQ: When initiating insulin glargine, administer 50% of the usual starting dose with slow titration and close monitoring of blood glucose (Ref).CRRT:SUBQ: Use is not recommended due to long duration of action; use of continuous IV insulin infusion is preferred in critically ill patients (Ref). Patients requiring basal insulin prior to their acute illness should be transitioned back to SUBQ basal insulin therapy (eg, insulin glargine) once the acute illness has stabilized and CRRT is discontinued (initially at a reduced dose based on patient specific factors) (Ref).PIRRT (eg, sustained, low-efficiency diafiltration): SUBQ: Use is not recommended in critically ill patients due to long duration of action; use of continuous IV insulin infusion is preferred in critically ill patients (Ref). When initiating insulin glargine in patients who have clinically stabilized and are receiving PIRRT as a transition back to intermittent hemodialysis, consider administering 50% of the usual starting dose with slow titration and close monitoring of blood glucose. Patients requiring basal insulin prior to their acute illness should be transitioned back to SUBQ basal insulin therapy (eg, insulin glargine) once the acute illness has stabilized (initially at a reduced dose based on patient-specific factors) (Ref).Dosing: Hepatic Impairment: AdultThere are no dosage adjustments provided in the manufacturer's labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.Dosing: Pediatric(For additional information see "Insulin glargine (including biosimilars): Pediatric drug information")Insulin glargine is a long-acting insulin. Insulin glargine is approximately equipotent to human insulin, but has a slower onset, no pronounced peak, and a longer duration of activity. Insulin doses should be individualized based on patient needs; adjustments may be necessary with changes in physical activity, meal patterns, acute illness, or with changes in renal or hepatic function. Insulin requirements vary dramatically between patients and dictates frequent monitoring and close medical supervision. Insulin regimens vary widely by region, practice, and institution; consult institution-specific guidelines.Type 1 diabetes mellitusType 1 diabetes mellitus: Children and Adolescents: Note: For basal insulin coverage, long-acting insulin analogs are preferred over insulin NPH due to decreased risk of hypoglycemia (Ref). Insulin glargine must be used in combination with a rapid or short-acting insulin. The daily doses presented are expressed as the total units/kg/day of all insulin formulations used.Insulin glargine-specific dosing: Note: All pediatric patients should have rapid-acting or regular insulin available for crisis management (Ref).Initial dose: Children ≥6 years and Adolescents:Lantus, Basaglar: SubQ: Approximately one-third of the total daily insulin requirement administered once daily; a rapid-acting or short-acting insulin should also be used to complete the balance (~2/3) of the total daily insulin requirement. Adjust dosage according to patient response.Toujeo: SubQ: Approximately one-third to one-half of the total daily insulin requirement administered once daily; a rapid-acting or short-acting insulin should also be used to complete the balance of the total daily insulin requirement. Adjust dosage according to patient response.General insulin dosing: Initial total daily insulin: SubQ: Initial: 0.4 to 0.5 units/kg/day in divided doses (Ref); Usual range: 0.4 to 1 units/kg/day in divided doses (Ref); lower doses (0.25 units/kg/day) may be used especially in young children to avoid potential hypoglycemia (Ref); higher doses may be necessary for some patients (eg, obese, concomitant steroids, puberty, sedentary lifestyle, following diabetic ketoacidosis presentation) (Ref).Usual total daily maintenance range: SubQ: Doses must be individualized; however, an estimate can be determined based on phase of diabetes and level of maturity (Ref).Partial remission phase (Honeymoon phase): <0.5 units/kg/day.Prepubertal children (not in partial remission):Infants ≥6 months and Children ≤6 years: 0.4 to 0.8 units/kg/day.Children ≥7 years: 0.7 to 1 units/kg/day.Pubescent Children and Adolescents: During puberty, requirements may substantially increase to >1 unit/kg/day and in some cases up to 2 units/kg/day.Division of daily insulin requirement (multiple daily injections): Basal insulin: Generally, ~30% to 50% of the total daily insulin is given as basal insulin (intermediate- or long-acting) in 1 to 2 daily injections (Ref).Prandial insulin: The remaining portion of the total daily dose is then divided and administered before or at mealtimes (depending on the formulation) as a rapid-acting (eg, aspart, glulisine, lispro) or short-acting (regular). In most type 1 patients, the use of a rapid-acting insulin analog is preferred over regular insulin to reduce hypoglycemia risk (Ref).Dosage titration: Treatment and monitoring regimens must be individualized to maintain premeal and bedtime glucose in target range; titrate dose to achieve glucose control and avoid hypoglycemia. Since combinations of agents are frequently used, dosage adjustment must address the individual component of the insulin regimen which most directly influences the blood glucose value in question, based on the known onset and duration of the insulin component.Surgical patients (Ref): Note: Diabetic patients should be scheduled as the first case of the day.Minor surgeries:Morning procedure: Administer the usual insulin glargine dose (if usually given in the morning); may consider reducing dose to 70% to 80% of usual dose if preoperative evaluation shows low morning blood glucose values. Alternatively, may administer IV insulin (regular) infusion; begin IV fluids containing dextrose; in general rapid acting insulin should be omitted until after surgery and patient is able to eat unless it is needed to correct significant hyperglycemia and/or significant ketone (>0.1 mmol/mol) production is present.Afternoon procedure: Administer the usual morning dose of insulin glargine (if usually given in the morning).Postprocedure: Once normal oral intake is achieved, resume usual insulin regimen; monitor closely due to risk of changes related to surgery (ie, postoperative stress, medication changes, inactivity).Major surgeries:Evening prior to surgery: If patient normally receives evening insulin doses, administer 50% to 100% of the usual evening and/or bedtime insulin glargine; patients on continuous subcutaneous insulin infusion (CSII) may continue normal insulin basal rates overnight; if there is a concern for hypoglycemia, basal rate may be reduced by 20% at ~3 am.Morning of surgery: Omit morning insulin (short- and long-acting) and start IV insulin (regular) infusion and IV fluids containing dextrose; patients on CSII should discontinue CSII when IV insulin infusion is started; once normal oral intake is resumed, then resume usual insulin regimen; monitor closely due to risk of changes related to surgery (ie, postoperative stress, medication changes, inactivity).Type 2 diabetes mellitusType 2 diabetes mellitus: Limited data available: Note: The goal of therapy is to achieve an HbA1c <7% as quickly as possible using the safe titration of medications.Toujeo-specific dosing: Children ≥6 years and Adolescents: SubQ: Initial: 0.2 units/kg/dose once daily.General insulin dosing:Newly diagnosed patients: Note: Recommended for use in metabolically unstable patients (eg, plasma glucose ≥250 mg/dL, HbA1c >8.5%, and symptoms excluding acidosis) while metformin is initiated and titrated (Ref); may also be used for patients with ketosis/ketoacidosis/ketonuria to correct the hyperglycemia and the metabolic derangement (Ref).Children ≥10 years and Adolescents: SubQ:Initial therapy: 0.25 to 0.5 units/kg/dose once daily; titrate every 2 to 3 days as needed based on plasma glucose; use in combination with lifestyle changes and metformin to achieve goals.Subsequent therapy:Glycemic goal achieved: Once initial goal reached, insulin should be slowly tapered over 2 to 6 weeks by decreasing the insulin dose by 10% to 30% every few days and the patient transitioned to lowest effective doses or metformin monotherapy if able (Ref).Failure to achieve glycemic goal: In patients who fail to achieve glycemic goals with insulin glargine (up to 1.5 units/kg/day) and maximum metformin dose, may consider dividing insulin glargine dose into multiple daily injections (eg, twice daily) and/or initiating prandial insulin (regular insulin or rapid-acting insulin) (Ref). Note: Insulin resistance is common with type 2 diabetes and doses >1.5 units/kg/day may be necessary to achieve glycemic control especially in patients with high A1c and patients in mid to late puberty; may consider use of more concentrated insulin glargine preparations (U-300 [Toujeo]) to avoid large volume injections that may affect medication adherence (Ref).Patients on established therapy: Note: Recommended for use when glycemic goals can no longer be met using metformin alone, or if contraindications or intolerable side effects of metformin develop (Ref).Children ≥10 years and Adolescents: SubQ: Initial: 0.25 to 0.5 units/kg/dose once daily; may be used alone or in combination with metformin (if not contraindicated); may be titrated as needed based on plasma glucose. If glycemic goals are not achieved at 1.5 units/kg/day evaluate adherence; if adherence confirmed, may consider dividing insulin glargine dose into multiple daily injections (eg, twice daily) and/or initiating prandial insulin (regular insulin or rapid-acting insulin) (Ref). Note: Insulin resistance is common with type 2 diabetes and doses >1.5 units/kg/day may be necessary to achieve glycemic control especially in patients with high A1c and patients in mid to late puberty; may consider use of more concentrated insulin glargine preparations (U-300 [Toujeo]) to avoid large volume injections that may affect medication adherence (Ref).Conversion to insulin glargine from NPH insulin: Children ≥2 years and Adolescents: SubQ: Note: Limited data available in children <6 years of age (Ref).Converting from once-daily NPH insulin to insulin glargine: May be substituted on an equivalent unit-per-unit basis.Converting from twice-daily NPH insulin to insulin glargine: Initial dose: Use 80% of the total daily dose of NPH (eg, 20% reduction); administer once daily; adjust dosage according to patient response.Conversion between Toujeo, Lantus, or Basaglar: Children ≥6 years and Adolescents: SubQ:Conversion from once-daily Toujeo to once-daily Lantus or once-daily Basaglar: Initial dose: Use 80% of the dose of Toujeo (eg, 20% reduction); adjust dosage according to patient blood glucose response.Conversion from once-daily Lantus to once-daily Toujeo or once-daily Basaglar: Initial dose: May be substituted on an equivalent unit-per-unit basis; however, generally a higher daily dosage of Toujeo will be required to achieve the same level of glycemic control as with Lantus.Conversion between Toujeo SoloStar and Toujeo Max SoloStar: Children ≥6 years and Adolescents: SubQ: If previous dose was an odd number, the dose should be increased or decreased by 1 unit to accommodate the 2 unit dosing increment on the Max SoloStar device.Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricThere are no dosage adjustments provided in manufacturer's labeling; insulin requirements are reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.Dosing: Hepatic Impairment: PediatricThere are no dosage adjustments provided in manufacturer's labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.Dosing: Older AdultRefer to adult dosing.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.[DSC] = Discontinued productSolution, Subcutaneous: Lantus: 100 units/mL (10 mL) [contains metacresol]Semglee: 100 units/mL (10 mL [DSC]) [contains metacresol]Semglee (yfgn): Insulin glargine-yfgn 100 units/mL (10 mL) [contains metacresol]Generic: 100 units/mL (10 mL); Insulin glargine-yfgn 100 units/mL (10 mL)Solution Pen-injector, Subcutaneous: Basaglar KwikPen: 100 units/mL (3 mL) [contains metacresol]Basaglar Tempo Pen: 100 units/mL (3 mL) [contains metacresol]Lantus SoloStar: 100 units/mL (3 mL) [contains metacresol]Semglee: 100 units/mL (3 mL [DSC]) [contains metacresol]Semglee (yfgn): Insulin glargine-yfgn 100 units/mL (3 mL) [contains metacresol]Toujeo Max SoloStar: 300 units/mL (3 mL) [contains metacresol]Toujeo SoloStar: 300 units/mL (1.5 mL) [contains metacresol]Generic: 100 units/mL (3 mL); Insulin glargine-yfgn 100 units/mL (3 mL)Generic Equivalent Available: USYesDosage Forms ConsiderationsBasaglar Tempo Pen: The Tempo Pen contains a component that allows for data connectivity when used with a compatible transmitter. Consult the prescribing information for additional information.Dosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution, Subcutaneous: Lantus: 100 units/mL (10 mL) [contains cresol]Solution Cartridge, Subcutaneous: Basaglar: 100 units/mL (3 mL) [contains metacresol]Lantus: 100 units/mL (3 mL)Solution Pen-injector, Subcutaneous: Basaglar KwikPen: 100 units/mL (3 mL) [contains metacresol]Lantus SoloStar: 100 units/mL (3 mL)Semglee: 100 units/mL (3 mL) [contains metacresol]Toujeo Doublestar: 300 units/mL (3 mL) [contains metacresol]Toujeo SoloStar: 300 units/mL (1.5 mL) [contains metacresol]Product AvailabilityBasaglar Tempo Pen: FDA approved November 2019; anticipated availability is currently unknown. The Tempo Pen contains a component that allows for data connectivity when used with a compatible transmitter. Consult the prescribing information for additional information.Rezvoglar: FDA approved December 2021; anticipated availability is currently unknown. Rezvoglar is approved as a biosimilar to Lantus.Administration: AdultSUBQ: Do not use if solution is viscous or cloudy; use only if clear and colorless with no visible particles. Insulin glargine should be administered consistently at the same time each day. Cold injections should be avoided. SUBQ administration is usually made into the thighs, arms, buttocks, or abdomen; absorption rates vary amongst injection sites; be consistent with area used while rotating injection sites within the same region to avoid lipodystrophy or localized cutaneous amyloidosis. Rotating from an injection site where lipodystrophy/cutaneous amyloidosis is present to an unaffected site may increase risk of hypoglycemia. Do not dilute or mix insulin glargine with any other insulin formulation or solution.Insulin glargine prefilled pens are available in concentrations of 100 units/mL and 300 units/mL. Prefilled pens are calibrated to display the actual insulin units administered (no dosage conversion needed) and will administer up to 80 units per injection, in 1 unit increments (Lantus SoloStar, Basaglar KwikPen, Basaglar Tempo Pen, Toujeo SoloStar, insulin glargine-yfgn [Semglee, generic]) or up to 160 units per injection, in 2 unit increments (Toujeo Max SoloStar, Toujeo DoubleStar [Canadian product]). Toujeo Max SoloStar and Toujeo DoubleStar (Canadian product) prefilled pens are only recommended for use in patients requiring at least 20 units of insulin glargine per day. Do not use a syringe to withdraw concentrated insulin glargine (300 units/mL) from a prefilled pen for administration. For prefilled pens, prime the needle with 2 units (Basaglar, Lantus, insulin glargine-yfgn [Semglee, generic]) or 3 units (Toujeo) or 4 units (Toujeo Max) before each injection (using a new needle). Once injected, continue to depress the button until the dial has returned to 0 and for an additional 5 seconds (Basaglar, Toujeo, Toujeo Max) or 10 seconds (Lantus, insulin glargine-yfgn [Semglee, generic]). Then, remove the needle. Cartridges (Canadian product) are to be used only with reusable pens recommended by the manufacturer (refer to product labeling).Administration: PediatricSubQ: Do not use if solution is viscous or cloudy; use only if clear and colorless with no visible particles. Administer consistently at the same time each day. Cold injections should be avoided. SubQ administration is usually made into the thighs, arms, buttocks, or abdomen; absorption rates vary amongst injection sites; be consistent with area used while rotating injection sites within the same region to avoid lipodystrophy or localized cutaneous amyloidosis. Rotating from an injection site where lipodystrophy/cutaneous amyloidosis is present to an unaffected site may increase risk of hypoglycemia. Do not mix with any other insulin or solution. Do not administer IV or in an insulin pump.Insulin glargine prefilled pens are available in concentrations of 100 units/mL and 300 units/mL. Prefilled pens are calibrated to display the actual insulin units administered (no dosage conversion needed) and will administer up to 80 units per injection, in 1 unit increments (eg, Lantus SoloStar, Basaglar KwikPen, Basaglar Tempo Pen, Toujeo SoloStar) or up to 160 units per injection, in 2 unit increments (eg, Toujeo Max SoloStar). Toujeo Max SoloStar prefilled pens are recommended for use in patients requiring at least 20 units of insulin glargine per day. Do not use a syringe to withdraw concentrated insulin glargine (300 units/mL) from a prefilled pen for administration. For prefilled pens, prime the needle according to manufacturer labeling (eg, Basaglar, Lantus, Semglee: 2 units; Toujeo: 3 units; Toujeo Max: 4 units) before each injection using a new needle. Once injected, continue to depress the button until the dial has returned to 0 and for an additional 5 seconds (eg, Basaglar, Toujeo, Toujeo Max) or 10 seconds (eg, Lantus, Semglee) and then, remove the needle.Use: Labeled IndicationsDiabetes mellitus, types 1 and 2, treatment: To improve glycemic control in pediatric patients ≥6 years of age and adults with type 1 diabetes mellitus; to improve glycemic control in pediatric patients ≥6 years of age (Toujeo only) and adults with type 2 diabetes mellitus.Note: Insulin glargine-yfgn (Semglee, generic) has been approved as a biosimilar to Lantus (insulin glargine).Use: Off-Label: AdultHyperglycemia in hospitalized patientsMedication Safety IssuesSound-alike/look-alike issues:Insulin glargine may be confused with insulin glulisine.Lantus may be confused with latanoprost, Latuda, Xalatan.Toujeo may be confused with Tanzeum [DSC], Tradjenta, Tresiba, Trulicity.High alert medication:The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error. Due to the number of insulin preparations, it is essential to identify/clarify the type of insulin to be used.Administration issues:Insulin glargine is a clear solution, but it is NOT intended for IV or IM administration.Other safety concerns:Cross-contamination may occur if insulin pens are shared among multiple patients. Steps should be taken to prohibit sharing of insulin pens.International issues:Lantus [US, Canada, and multiple international markets] may be confused with Lanvis brand name for thioguanine [Canada and multiple international markets].Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidence rates are from glargine administered with concomitant antidiabetic agents (insulin or oral products).>10%:Cardiovascular: Hypertension (20%), peripheral edema (≤20%)Endocrine & metabolic: Severe hypoglycemia (Type I on combination regimens: 4% to 69%; Type II on combination regimens: ≤37%; monotherapy in adults ≥50 years old: 6% [ORIGIN trial])Gastrointestinal: Diarrhea (11%)Genitourinary: Urinary tract infection (11%)Immunologic: Antibody development (12% to 44%)Infection: Infection (9% to 24%), influenza (19%)Nervous system: Depression (11%)Neuromuscular & skeletal: Arthralgia (14%), back pain (13%), limb pain (13%)Ophthalmic: Cataract (18%)Respiratory: Bronchitis (15%), cough (12%), nasopharyngitis (6% to 16%), sinusitis (19%), upper respiratory tract infection (5% to 29%)1% to 10%:Local: Pain at injection site (3%)Nervous system: Headache (6% to 10%)Ophthalmic: Retinal vascular disease (6%)Respiratory: Pharyngitis (children and adolescents: 8%), rhinitis (children and adolescents: 5%)Miscellaneous: Accidental injury (6%)<1%: Local: Injection-site reaction (including erythema at injection site, hypertrophy at injection site, inflammation at injection site, injection-site pruritus, lipoatrophy at injection site, localized edema, swelling at injection site, urticaria at injection site)Frequency not defined:Endocrine & metabolic: Sodium retention, weight gainHypersensitivity: Anaphylaxis, angioedema, hypersensitivity reactionPostmarketing: Endocrine & metabolic: Amyloidosis (localized cutaneous at injection site)ContraindicationsHypersensitivity to insulin glargine or any component of the formulation; during episodes of hypoglycemiaDocumentation of allergenic cross-reactivity for insulin is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.Warnings/PrecautionsConcerns related to adverse effects:• Glycemic control: Hyper- or hypoglycemia may result from changes in insulin strength, manufacturer, type, and/or administration method. The most common adverse effect of insulin is hypoglycemia. The timing of hypoglycemia differs among various insulin formulations. Hypoglycemia may result from changes in meal pattern (eg, macronutrient content, timing of meals), changes in the level of physical activity, increased work or exercise without eating, or changes to coadministered medications. Use of long-acting insulin preparations (eg, insulin degludec, insulin detemir, insulin glargine) may delay recovery from hypoglycemia. Patients with renal or hepatic impairment may be at a higher risk. Symptoms differ in patients and may change over time in the same patient; awareness may be less pronounced in those with long-standing diabetes, diabetic neuropathy, patients taking beta-blockers, or in those who experience recurrent hypoglycemia. Profound and prolonged episodes of hypoglycemia may result in convulsions, unconsciousness, temporary or permanent brain damage, or even death. Insulin requirements may be altered during illness, emotional disturbances, or other stressors. Instruct patients to use caution with ethanol; may increase risk of hypoglycemia.• Hypersensitivity: Severe, life-threatening allergic reactions, including anaphylaxis, may occur. If hypersensitivity reactions occur, discontinue therapy.• Hypokalemia: Insulin (especially IV insulin) causes a shift of potassium from the extracellular space to the intracellular space, possibly producing hypokalemia. If left untreated, hypokalemia may result in respiratory paralysis, ventricular arrhythmia and even death. Use with caution in patients at risk for hypokalemia (eg, loop diuretic use). Monitor serum potassium and supplement potassium when necessary.Disease-related concerns:• Bariatric surgery:– Type 2 diabetes, hypoglycemia: Closely monitor insulin dose requirement throughout active weight loss with a goal of eliminating antidiabetic therapy or transitioning to agents without hypoglycemic potential; hypoglycemia after gastric bypass, sleeve gastrectomy, and gastric band may occur (Mechanick 2019). Insulin secretion and sensitivity may be partially or completely restored early after these procedures (gastric bypass is most effective, followed by sleeve and finally band) (Korner 2009; Peterli 2012). Monitoring of hospital insulin requirements is recommended to guide discharge insulin dose. Rates and timing of type 2 diabetes improvement and resolution vary widely by patient; insulin dose reduction of 75% has been suggested after gastric bypass for patients without severe β-cell failure (fasting c-peptide <0.3 nmol/L) (Cruijsen 2014).– Weight gain: Insulin therapy is preferred if antidiabetic therapy is required during the perioperative period (Mechanick 2019). Evaluate risk versus benefit of long-term postoperative use, and consider alternative therapy due to potential for insulin-induced weight gain (Apovian 2015).• Cardiac disease: Concurrent use with peroxisome proliferator-activated receptor (PPAR)-gamma agonists, including thiazolidinediones, may cause dose-related fluid retention and lead to or exacerbate heart failure (HF), particularly when used in combination with insulin. If PPAR-gamma agonists are prescribed, monitor for signs and symptoms of HF. If HF develops, consider PPAR-gamma agonist dosage reduction or therapy discontinuation.• Diabetic ketoacidosis: Should not be used in patients with diabetic ketoacidosis; use of a rapid-acting or short-acting insulin is required.• Hepatic impairment: Use with caution in patients with hepatic impairment. Dosage requirements may be reduced.• Renal impairment: Use with caution in patients with renal impairment. Dosage requirements may be reduced.Special populations:• Hospitalized patients: Prolonged use of a sliding scale insulin regimen in the inpatient setting is strongly discouraged. In the critical care setting, continuous IV insulin infusion (insulin regular) has been shown to best achieve glycemic targets. In noncritically ill patients with either poor oral intake or taking nothing by mouth, basal insulin use is preferred, with correctional doses (insulin regular or rapid-acting insulin) as needed. In noncritically ill patients with adequate nutritional intake, a combination of basal insulin along with nutritional and correctional components (insulin regular or rapid-acting insulin) is preferred. An effective insulin regimen will achieve the goal glucose range without the risk of severe hypoglycemia. A blood glucose value <70 mg/dL should prompt a treatment regimen review and change, if necessary, to prevent further hypoglycemia (ADA 2022).Dosage form specific issues:• Multiple dose injection pens: According to the Centers for Disease Control and Prevention (CDC), pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).Other warnings/precautions:• Administration: Insulin glargine is a clear solution, but it is NOT intended for IV or IM administration or via an insulin pump.• Patient education: Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.Metabolism/Transport EffectsNone known.Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Alpha-Glucosidase Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with an alpha-glucosidase inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modificationAlpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyAndrogens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyAntidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapyBeta-Blockers (Beta1 Selective): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyBeta-Blockers (Nonselective): May enhance the hypoglycemic effect of Insulins. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Insulins. Risk C: Monitor therapyBortezomib: May enhance the therapeutic effect of Antidiabetic Agents. Bortezomib may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyDipeptidyl Peptidase-IV Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modificationDirect Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyEdetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulins. Risk C: Monitor therapyEtilefrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyGlucagon-Like Peptide-1 Agonists: May enhance the hypoglycemic effect of Insulins. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modificationGuanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapyHerbal Products with Glucose Lowering Effects: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapyHyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyHypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Risk C: Monitor therapyHypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.Risk C: Monitor therapyLiraglutide: May enhance the hypoglycemic effect of Insulins. Management: Consider reducing the liraglutide dose if coadministered with insulin. Prescribing information for the Saxenda brand of liraglutide recommends a dose decrease of 50%. Monitor blood glucose for hypoglycemia. Risk D: Consider therapy modificationMacimorelin: Insulins may diminish the diagnostic effect of Macimorelin.Risk X: Avoid combinationMaitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyMetreleptin: May enhance the hypoglycemic effect of Insulins. Management: Insulin dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin.Monitor closely for signs and symptoms of hypoglycemia. Risk D: Consider therapy modificationMonoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyPegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyPioglitazone: May enhance the adverse/toxic effect of Insulins. Specifically, the risk for hypoglycemia, fluid retention, and heart failure may be increased with this combination. Management: If insulin is combined with pioglitazone, consider insulin dose reductions to avoid hypoglycemia. Monitor patients for fluid retention and signs/symptoms of heart failure, and consider pioglitazone dose reduction or discontinuation if heart failure occurs Risk D: Consider therapy modificationPramlintide: May enhance the hypoglycemic effect of Insulins. Management: Upon initiation of pramlintide, decrease mealtime insulin dose by 50% to reduce the risk of hypoglycemia. Monitor blood glucose frequently and individualize further insulin dose adjustments based on glycemic control. Risk D: Consider therapy modificationProthionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapyQuinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapyRitodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyRosiglitazone: Insulins may enhance the adverse/toxic effect of Rosiglitazone. Specifically, the risk of fluid retention, heart failure, and hypoglycemia may be increased with this combination.Risk X: Avoid combinationSalicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapySelective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapySodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modificationThiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapyReproductive ConsiderationsPatients with diabetes mellitus who wish to conceive should use adequate contraception until glycemic control is achieved (ADA 2022). Because insulin glargine has an increased affinity to the insulin-like growth factor (IGF-I) receptor, there are theoretical concerns that it may contribute to adverse events when used during pregnancy (Blumer 2013). Patients who are stable on insulin glargine prior to conception may continue it during pregnancy. Theoretical concerns of adverse events associated with insulin glargine during pregnancy should be discussed prior to conception (Blumer 2013).Pregnancy ConsiderationsBecause insulin glargine has an increased affinity to the insulin-like growth factor (IGF-I) receptor, there are theoretical concerns that it may contribute to adverse events when used during pregnancy (Blumer 2013).Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major malformations, stillbirth, and macrosomia. To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2022; Blumer 2013).Due to pregnancy-induced physiologic changes, insulin requirements tend to increase as pregnancy progresses, requiring frequent monitoring and dosage adjustments. Following delivery, insulin requirements decrease rapidly (ACOG 201 2018; ADA 2022).Insulin is the preferred treatment of type 1 and type 2 diabetes mellitus in pregnancy, as well as gestational diabetes mellitus when pharmacologic therapy is needed (ACOG 190 2018; ACOG 201 2018; ADA 2022). Pregnancy outcomes are similar following maternal use of insulin glargine and NPH insulin in pregnant patients with type 1 diabetes mellitus. Outcomes are likely to be similar in pregnant patients with type 2 diabetes and insulin glargine may be used when clinically indicated (ACOG 201 2018).Breastfeeding ConsiderationsIn a study using insulin glargine, both exogenous and endogenous insulin were present in breast milk (Whitmore 2012). Insulin is not systemically absorbed via breast milk but may provide local benefits to the infant GI tract (Anderson 2018).Appropriate glycemic control is required for the establishment of lactation in patients with diabetes mellitus (Anderson 2018). Breastfeeding provides metabolic benefits to mothers with type 1, type 2, and gestational diabetes mellitus as well as their infants; therefore, breastfeeding is encouraged (ACOG 201 2018; ADA 2022; Blumer 2013). Breastfeeding also influences maternal glucose tolerance; close monitoring of patients treated with insulin is recommended as dose adjustments may be required (ADA 2022; Anderson 2018). A small snack before breastfeeding may help decrease the risk of hypoglycemia in patients with pregestational diabetes (ACOG 201 2018; Reader 2004). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.Dietary ConsiderationsIndividualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.Monitoring ParametersDiabetes mellitus: Blood glucose (individualize frequency based on treatment regimen, hypoglycemia risk, and other patient-specific factors) (ADA 2022); electrolytes; renal function; hepatic function; weight.Gestational diabetes mellitus: Blood glucose 4 times daily (1 fasting and 3 postprandial) until well controlled, then as appropriate (ACOG 2018).Hospitalized patients: In patients who are eating, monitor blood glucose before meals and at bedtime; in patients who are not eating or are receiving continuous enteral feeds, monitor blood glucose every 4 to 6 hours (ADA 2022; ES [Umpierrez 2012]). More frequent monitoring may be required in some cases (eg, recurrent hypoglycemia, changes in nutrition, medication changes affecting glycemic control) (ES [Umpierrez 2012]).HbA1c: Monitor at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; monitor quarterly in patients in whom treatment goals have not been met, or with therapy change. Note: In patients prone to glycemic variability (eg, patients with insulin deficiency), or in patients whose HbA1c is discordant with serum glucose levels or symptoms, consider evaluating HbA1c in combination with blood glucose levels and/or a glucose management indicator (ADA 2022; KDIGO 2020).Reference RangeRecommendations for glycemic control in patients with diabetes and/or hyperglycemia:Nonpregnant adults (ADA 2022):HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics). Note: In patients using a continuous glucose monitoring system, a goal of time in range >70% with time below range <4% is recommended and is similar to a goal HbA1c <7%.Preprandial capillary blood glucose: 80 to 130 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics)Peak postprandial capillary blood glucose (~1 to 2 hours after a meal): <180 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics)Older adults (≥65 years of age) (ADA 2022):Note: Consider less strict targets in patients who are using insulin and/or insulin secretagogues (sulfonylureas, meglitinides) (ES [LeRoith 2019]).HbA1c: <7% to 7.5% (healthy); <8% to 8.5% (complex/intermediate health). Note: Individualization may be appropriate based on patient and caregiver preferences and/or presence of cognitive impairment. In patients with very complex or poor health (ie, limited remaining life expectancy), consider making therapy decisions based on avoidance of hypoglycemia and symptomatic hyperglycemia rather than HbA1c level.Preprandial capillary blood glucose: 80 to 130 mg/dL (healthy); 90 to 150 mg/dL (complex/intermediate health); 100 to 180 mg/dL (very complex/poor health).Bedtime capillary blood glucose: 80 to 180 mg/dL (healthy); 100 to 180 mg/dL (complex/intermediate health); 110 to 200 mg/dL (very complex/poor health).Pregnant patients:HbA1c: Pregestational diabetes (type 1 or type 2) (ADA 2022):Preconception (patients planning for pregnancy): <6.5%.During pregnancy <6% (if can be achieved without significant hypoglycemia) or <7% if needed to prevent hypoglycemia.Capillary blood glucose: Note: Less stringent targets may be appropriate if goals cannot be achieved without causing significant hypoglycemia (ADA 2022).Gestational diabetes mellitus (ACOG 2018; ADA 2022):Fasting: <95 mg/dL.Postprandial: <140 mg/dL (at 1 hour) or <120 mg/dL (at 2 hours).Pregestational diabetes mellitus (type 1 or type 2) (ADA 2022):Fasting: 70 to 95 mg/dL.Postprandial: 110 to 140 mg/dL (at 1 hour) or 100 to 120 mg/dL (at 2 hours).Hospitalized adult patients (ADA 2022): Target glucose range: 140 to 180 mg/dL (majority of critically ill and noncritically ill patients; <140 mg/dL may be appropriate for selected patients, if it can be achieved without excessive hypoglycemia).Perioperative care in adult patients (ADA 2022): Target glucose range during perioperative period: Consider targeting 80 to 180 mg/dL.Children and adolescents:Preprandial glucose: 70 to 130 mg/dL (ISPAD [Dimeglio 2018]).Postprandial glucose: 90 to 180 mg/dL (ISPAD [Dimeglio 2018]).Bedtime/overnight glucose: 80 to 140 mg/dL (ISPAD [Dimeglio 2018]).HbA1c: <7%; target should be individualized; a more stringent goal (<6.5%) may be reasonable if it can be achieved without significant hypoglycemia; less aggressive goals (<7.5% or <8%) may be appropriate in patients who cannot articulate symptoms of hypoglycemia, cannot check glucose frequently, have a history of severe hypoglycemia, or have extensive comorbid conditions (ADA 2022; ISPAD [Dimeglio 2018]).Surgical patients (ISPAD [Jefferies 2018]):Intraoperative: 90 to 180 mg/dL.ICU, postsurgery: 140 to 180 mg/dL.Classification of hypoglycemia (ADA 2022):Level 1: 54 to 70 mg/dL; hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.Level 2: <54 mg/dL; threshold for neuroglycopenic symptoms; requires immediate action.Level 3: Hypoglycemia associated with a severe event characterized by altered mental and/or physical status requiring assistance.Mechanism of ActionInsulin acts via specific membrane-bound receptors on target tissues to regulate metabolism of carbohydrate, protein, and fats. Target organs for insulin include the liver, skeletal muscle, and adipose tissue.Within the liver, insulin stimulates hepatic glycogen synthesis. Insulin promotes hepatic synthesis of fatty acids, which are released into the circulation as lipoproteins. Skeletal muscle effects of insulin include increased protein synthesis and increased glycogen synthesis. Within adipose tissue, insulin stimulates the processing of circulating lipoproteins to provide free fatty acids, facilitating triglyceride synthesis and storage by adipocytes; also directly inhibits the hydrolysis of triglycerides. In addition, insulin stimulates the cellular uptake of amino acids and increases cellular permeability to several ions, including potassium, magnesium, and phosphate. By activating sodium-potassium ATPases, insulin promotes the intracellular movement of potassium.Normally secreted by the pancreas, insulin products are manufactured for pharmacologic use through recombinant DNA technology using either E. coli or Saccharomyces cerevisiae. Insulin glargine differs from human insulin by adding two arginines to the C-terminus of the B-chain in addition to containing glycine at position A21 in comparison to the asparagine found in human insulin. Insulins are categorized based on the onset, peak, and duration of effect (eg, rapid-, short-, intermediate-, and long-acting insulin). Insulin glargine is a long-acting insulin analog.Pharmaco*kineticsNote: Onset and duration of hypoglycemic effects depend upon the route of administration (absorption and onset of action are more rapid after deeper IM injections than after SUBQ), site of injection (onset and duration are progressively slower with SUBQ injection into the abdomen, arm, buttock, or thigh respectively), volume and concentration of injection, and the preparation administered. Rate of absorption, onset, and duration of activity may be affected by exercise, presence of lipodystrophy, local blood supply, and/or temperature.Onset of action: Lantus: 3 to 4 hours; Toujeo: 6 hours.Duration: Basaglar, Lantus, insulin glargine-yfgn (Semglee, generic): Generally, 24 hours or longer; reported range (Lantus): 10.8 to >24 hours (up to ~30 hours documented in some studies) (Heinemann 2000; Heise 2020); Toujeo: >24 hours.Absorption: Slow; upon injection into the subcutaneous tissue, microprecipitates form which allow small amounts of insulin glargine to release over time.Metabolism: Partially metabolized in the subcutaneous depot at the carboxyl terminus of the B chain to form two active metabolites, M1 (21A-Gly-insulin) and M2 (21A-Gly-des-30B-Thr-insulin).Time to peak, plasma: Basaglar, Median: ~12 hours (manufacturer's labeling); Lantus, Semglee: Mean: subtle peak at ~10 to 12 hours (Heise 2020); Toujeo: Median: 12 to 16 hours following a single dose (maximum glucose lowering effect may take up to 5 days with repeat dosing) (manufacturer's labeling).Pharmaco*kinetics: Additional ConsiderationsAltered kidney function: Insulin clearance may be reduced in patients with impaired renal function.Pricing: USSolution (Insulin Glargine Subcutaneous)100 units/mL (per mL): $13.61Solution (Insulin Glargine-yfgn Subcutaneous)100 units/mL (per mL): $11.84Solution (Lantus Subcutaneous)100 units/mL (per mL): $34.03Solution (Semglee (yfgn) Subcutaneous)100 units/mL (per mL): $32.33Solution Pen-injector (Basaglar KwikPen Subcutaneous)100 units/mL (per mL): $26.11Solution Pen-injector (Basaglar Tempo Pen Subcutaneous)100 units/mL (per mL): $26.11Solution Pen-injector (Insulin Glargine-yfgn Subcutaneous)100 units/mL (per mL): $11.84Solution Pen-injector (Lantus SoloStar Subcutaneous)100 units/mL (per mL): $34.02Solution Pen-injector (Semglee (yfgn) Subcutaneous)100 units/mL (per mL): $32.32Solution Pen-injector (Toujeo Max SoloStar Subcutaneous)300 units/mL (per mL): $103.66Solution Pen-injector (Toujeo SoloStar Subcutaneous)300 units/mL (per mL): $103.65Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalAbasaglar (BE, DK, EE, ES, GB, HR, LT, NL, NO, PL, PT, RO, SK);Abasria (MT);Basagine (PH);Basaglar (SG, TW);Basaglar KwikPen (PH);Basalog (MY);Basalog One (MY);Bonglixan (CR, DO, GT, HN, MX, NI, PA, SV);Endulin (ZW);Ezelin (ID);Glargilin (PH);Glaritus (PH, VN);Glysolin G (PH);Insulet GN (BD);Lantus (AE, AR, AT, AU, BB, BE, BG, BH, BM, BR, BS, BZ, CH, CL, CO, CR, CY, CZ, DE, DK, DO, EC, EE, ES, FI, FR, GB, GR, GT, GY, HK, HN, HR, HU, ID, IE, IL, IN, IS, IT, JM, JO, KR, KW, LB, LK, LT, LU, LV, MT, MX, MY, NI, NL, NO, NZ, PA, PE, PH, PK, PL, PR, PT, PY, QA, RO, RU, SA, SE, SG, SI, SK, SR, SV, TH, TR, TT, TW, UA, UY, VE, VN, ZW);Lantus XR (ID, JP);Lusduna (BE);Optisulin (CZ, EE, FI, IE, IN, LT, MT, NL, PL, PT, RO);Podevta (PH);Sansulin Log-G (ID);Semglee (AT, AU, CZ, DK, EE, GB, HR, HU, LT, LU, LV, NL, PT, SK);Toujeo (BE, BH, SG, TW, UA);Tuojeo (GB, HK, HR, IE, MY, NL, PH, SK, TH, VN);Vibrenta (BD)For country code abbreviations (show table)Alemzadeh R, Berhe T, Wyatt DT. Flexible insulin therapy with glargine insulin improved glycemic control and reduced severe hypoglycemia among preschool-aged children with type 1 diabetes mellitus. Pediatrics. 2005;115(5):1320-1324. doi:10.1542/peds.2004-1439 [PubMed 15867042]American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins—Obstetrics. Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol. 2018;131(2):e49-e64. [PubMed 29370047]American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. Practice Bulletin No. 201: Pregestational diabetes mellitus. Obstet Gynecol. 2018;132(6):e228-e248. doi:10.1097/AOG.0000000000002960 [PubMed 30461693]American Diabetes Association (ADA). Diabetes Care. 2019;42(suppl 1):S1-S193. http://care.diabetesjournals.org/content/42/Supplement_1. Accessed April 11, 2019.American Diabetes Association (ADA). Standards of medical care in diabetes–2020. Diabetes Care. 2020;43(suppl 1):S1-S212. https://care.diabetesjournals.org/content/43/Supplement_1. Accessed January 22, 2020.American Diabetes Association (ADA). Standards of medical care in diabetes–2022. Diabetes Care. 2022;45(suppl 1):S1-S255. https://diabetesjournals.org/care/issue/45/Supplement_1. Accessed September 19, 2022.Anderson PO. Treating diabetes during breastfeeding. Breastfeed Med. 2018;13(4):237-239. doi:10.1089/bfm.2018.0036 [PubMed 29608329]Apovian CM, Aronne LJ, Bessesen DH, et al; Endocrine Society. Pharmacological management of obesity: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(2):342-362. doi:10.1210/jc.2014-3415 [PubMed 25590212]Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th ed. American College of Physicians; 2007:42.Arslanian S, Bacha F, Grey M, Marcus MD, White NH, Zeitler P. Evaluation and management of youth-onset type 2 diabetes: a position statement by the American Diabetes Association. Diabetes Care. 2018;41(12):2648-2668. [PubMed 30425094]Ashwell SG, Gebbie J, Home PD. Twice-daily compared with once-daily insulin glargine in people with type 1 diabetes using meal-time insulin aspart. Diabet Med. 2006;23(8):879-886. doi:10.1111/j.1464-5491.2006.01913.x [PubMed 16911626]Baldwin D, Zander J, Munoz C, et al. A randomized trial of two weight-based doses of insulin glargine and glulisine in hospitalized subjects with type 2 diabetes and renal insufficiency. Diabetes Care. 2012;35(10):1970-1974. doi:10.2337/dc12-0578 [PubMed 22699288]Barnett AH. Insulin glargine in the treatment of type 1 and type 2 diabetes. Vasc Health Risk Manag. 2006;2(1):59-67. [PubMed 17319470]Basaglar (insulin glargine) [prescribing information]. Indianapolis, IN: Eli Lilly and Company; July 2021.Basaglar (insulin glargine) [product monograph]. Toronto, Ontario, Canada: Eli Lilly Canada Inc; March 2021.Based on expert opinion.Beck JK, Cogen FR. Outpatient management of pediatric type 1 diabetes. J Pediatr Pharmacol Ther. 2015;20(5):344-357. doi:10.5863/1551-6776-20.5.344 [PubMed 26472948]Biesenbach G, Raml A, Schmekal B, Eichbauer-Sturm G. Decreased insulin requirement in relation to GFR in nephropathic type 1 and insulin-treated type 2 diabetic patients. Diabet Med. 2003;20(8):642-645. doi:10.1046/j.1464-5491.2003.01025.x [PubMed 12873291]Blumer I, Hadar E, Hadden DR, et al. Diabetes and pregnancy: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(11):4227-4249. [PubMed 24194617]Centers for Disease Control and Prevention (CDC). CDC clinical reminder: insulin pens must never be used for more than one person. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/injectionsafety/clinical-reminders/insulin-pens.html. Updated January 5, 2012. Accessed January 9, 2012.Chiang JL, Kirkman MS, Laffel LM, et al; Type 1 Diabetes Sourcebook Authors. Type 1 diabetes through the life span: a position statement of the American Diabetes Association. Diabetes Care. 2014;37(7):2034-54. doi:10.2337/dc14-1140 [PubMed 24935775]Clement S, Braithwaite SS, Magee MF, et al; American Diabetes Association Diabetes in Hospitals Writing Committee. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27(2):553-591. doi:10.2337/diacare.27.2.553 [PubMed 14747243]Colino E, López-Capapé M, Golmayo L, et al. Therapy with insulin glargine (Lantus) in toddlers, children and adolescents with type 1 diabetes. Diabetes Res Clin Pract. 2005;70(1):1-7. doi:10.1016/j.diabres.2005.02.004 [PubMed 16126116]Copeland KC, Silverstein J, Moore KR, et al; American Academy of Pediatrics. Management of newly diagnosed type 2 diabetes mellitus (T2DM) in children and adolescents. Pediatrics. 2013;131(2):364-382. doi:10.1542/peds.2012-3494 [PubMed 23359574]Couper JJ, Haller MJ, Greenbaum CJ, et al. ISPAD clinical practice consensus guidelines 2018: stages of type 1 diabetes in children and adolescents. Pediatr Diabetes. 2018;19(suppl 27):20-27. [PubMed 30051639]Cruijsen M, Koehestani P, Huttjes S, Leenders K, Janssen I, de Boer H. Perioperative glycaemic control in insulin-treated type 2 diabetes patients undergoing gastric bypass surgery. Neth J Med. 2014;72(4):202-209. [PubMed 24829176]Danne T, Phillip M, Buckingham BA, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Insulin treatment in children and adolescents with diabetes. Pediatr Diabetes. 2018;19(suppl 27):115-135. doi:10.1111/pedi.12718 [PubMed 29999222]Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41(12):2669-2701. doi:10.2337/dci18-0033 [PubMed 30291106]DiMeglio LA, Acerini CL, Codner E, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Glycemic control targets and glucose monitoring for children, adolescents, and young adults with diabetes. Pediatr Diabetes. 2018;19(suppl 27):105-114. [PubMed 30058221]Eledrisi M, Suleiman NN, Salameh O, et al. Twice-daily insulin glargine for patients with uncontrolled type 2 diabetes mellitus. J Clin Transl Endocrinol. 2018;15:35-36. doi:10.1016/j.jcte.2018.12.002 [PubMed 30619716]Garber AJ, Handelsman Y, Grunberger G, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2020 executive summary. Endocr Pract. 2020;26(1):107-139. doi:10.4158/CS-2019-0472 [PubMed 32022600]Handelsman Y, Bloomgarden ZT, Grunberger G, et al. American Association of Clinical Endocrinologists and American College of Endocrinology - clinical practice guidelines for developing a diabetes mellitus comprehensive care plan - 2015. Endocr Pract. 2015;21(suppl 1):1-87. doi:10.4158/EP15672.GLSUPPL [PubMed 25869408]Heinemann L, Hompesch B, Linkeschova R, et al. Time-Action Profile of the Long-Acting Insulin Analog Insulin Glargine (HOE901) in Comparison With Those of NPH and Placebo. Diabetes Care. 2000;23(5):644-9. [PubMed 10834424]Heise T, Donnelly C, Barve A, Aubonnet P. Pharmaco*kinetic and pharmacodynamic bioequivalence of proposed biosimilar MYL-1501D with US and European insulin glargine formulations in patients with type 1 diabetes mellitus. Diabetes Obes Metab. 2020;22(4):521-529. doi:10.1111/dom.13919 [PubMed 31724253]Housel AK, Shaw RF, Waterbury NV. Glucose control in patients with type 2 diabetes based on frequency of insulin glargine administration. Diabetes Res Clin Pract. 2010;88(2):e17-e19. doi:10.1016/j.diabres.2010.01.020 [PubMed 20144488]International Diabetes Federation, International Society for Pediatric and Adolescent Diabetes. Global IDF/ISPAD Guideline for Diabetes in Childhood and Adolescence. 2011. Available at http://www.idf.org/global-idfispad-guideline-diabetes-childhood-and-adolescence. Last accessed: October 21, 2013.Inzucchi SE. Management of diabetes mellitus in hospitalized patients. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 7, 2021.Jacobi J, Bircher N, Krinsley J, et al. Guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients. Crit Care Med. 2012;40(12):3251-3276. doi:10.1097/CCM.0b013e3182653269 [PubMed 23164767]Jefferies C, Rhodes E, Rachmiel M, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Management of children and adolescents with diabetes requiring surgery. Pediatr Diabetes. 2018;19(suppl 27):227-236. doi:10.1111/pedi.12733 [PubMed 30039617]Khan NA, Ghali WA, Cagliero E. Perioperative management of blood glucose in adults with diabetes mellitus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 15, 2022.Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2020;98(4S):S1-S115. doi:10.1016/j.kint.2020.06.019 [PubMed 32998798]Kirkman M, Briscoe VJ, Clark N, et al. Diabetes in Older Adults: A Consensus Report. J Am Geriatr Soc. 2012. doi:10.1111/jgs.12035 [PubMed 23106132]Kocurek B, Cryar K. Information for health care professionals switching between insulin products in disaster response situations. Approved by the American Diabetes Association, the Endocrine Society, and JDRF. https://www.diabetes.org/sites/default/files/2019-08/switching-between-insulin.pdf. Published August 2018.Korner J, Inabnet W, Febres G, et al. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes (Lond). 2009;33(7):786-795. doi:10.1038/ijo.2009.79 [PubMed 19417773]Kulozik F, Hasslacher C. Insulin requirements in patients with diabetes and declining kidney function: differences between insulin analogues and human insulin? Ther Adv Endocrinol Metab. 2013;4(4):113-121. doi:10.1177/2042018813501188 [PubMed 23997930]Lantus (insulin glargine) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis US LLC; January 2021.Lantus (insulin glargine) [product monograph]. Laval, Quebec, Canada: Sanofi-Aventis Canada Inc; December 2021.LeRoith D, Biessels GJ, Braithwaite SS, et al. Treatment of diabetes in older adults: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2019;104(5):1520-1574. doi:10.1210/jc.2019-00198 [PubMed 30903688]McCall AL. Insulin therapy and hypoglycemia. Endocrinol Metab Clin North Am. 2012;41(1):57-87. doi:10.1016/j.ecl.2012.03.001 [PubMed 22575407]Mechanick JI, Apovian C, Brethauer S, et al. Clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures - 2019 update: cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, the Obesity Society, American Society for Metabolic & Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists - executive summary. Endocr Pract. 2019;25(12):1346-1359. doi:10.4158/GL-2019-0406 [PubMed 31682518]Moghissi ES, Korytkowski MT, DiNardo M, et al; American Association of Clinical Endocrinologists; American Diabetes Association. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Endocr Pract. 2009;15(4):353-369. doi:10.4158/EP09102.RA [PubMed 19454396]Peterli R, Steinert RE, Woelnerhanssen B, et al. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes Surg. 2012;22(5):740-748. doi:10.1007/s11695-012-0622-3 [PubMed 22354457]Peters AP, Laffel L, eds. Type 1 Diabetes Sourcebook. American Diabetes Association; 2013.Pichardo-Lowden A, Gabbay RA. Management of hyperglycemia during the perioperative period. Curr Diab Rep. 2012;12(1):108-118. doi:10.1007/s11892-011-0239-2 [PubMed 22086363]Rahhal MN, Gharaibeh NE, Rahimi L, Ismail-Beigi F. Disturbances in insulin-glucose metabolism in patients with advanced renal disease with and without diabetes. J Clin Endocrinol Metab. 2019;104(11):4949-4966. doi:10.1210/jc.2019-00286 [PubMed 31162534]Rajput R, Sinha B, Majumdar S, Shunmugavelu M, Bajaj S. Consensus statement on insulin therapy in chronic kidney disease. Diabetes Res Clin Pract. 2017;127:10-20. doi:10.1016/j.diabres.2017.02.032 [PubMed 28315574]Rashid K, Rehman KU, Anwer MS, Qureshi A, Basharat RA. Insulin requirement in diabetic patients with chronic renal failure due to diabetic nephropathy. Biomedica. 2004;20:79–84.Reader D, Franz MJ. Lactation, diabetes, and nutrition recommendations. Curr Diab Rep. 2004;4(5):370-376. [PubMed 15461903]Refer to manufacturer's labeling.Reid T, Gao L, Gill J, et al. How much is too much? Outcomes in patients using high-dose insulin glargine. Int J Clin Pract. 2016;70(1):56-65. doi:10.1111/ijcp.12747 [PubMed 26566714]Semglee (insulin glargine) [prescribing information]. Morgantown, WV: Mylan; October 2022.Silverstein J, Klingensmith G, Copeland K, et al; American Diabetes Association. Care of children and adolescents with type 1 diabetes: a statement of the American Diabetes Association. Diabetes Care. 2005;28(1):186-212. [PubMed 15616254]Sobngwi E, Enoru S, Ashuntantang G, et al. Day-to-day variation of insulin requirements of patients with type 2 diabetes and end-stage renal disease undergoing maintenance hemodialysis. Diabetes Care. 2010;33(7):1409-1412. doi:10.2337/dc09-2176 [PubMed 20215452]Sundberg F, Barnard K, Cato A, et al. ISPAD Guidelines. Managing diabetes in preschool children. Pediatr Diabetes. 2017;18(7):499-517. doi:10.1111/pedi.12554 [PubMed 28726299]Toujeo (insulin glargine) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis US LLC; December 2020.Toujeo SoloStar and Toujeo DoubleStar (insulin glargine) [product monograph]. Laval, Quebec, Canada: Sanofi-Aventis Canada Inc; May 2020.Umpierrez GE, Hellman R, Korytkowski MT, et al. Management of hyperglycemia in hospitalized patients in non-critical care setting: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(1):16-38. doi:10.1210/jc.2011-2098 [PubMed 22223765]Umpierrez GE, Skolnik N, Dex T, Traylor L, Chao J, Shaefer C. When basal insulin is not enough: A dose-response relationship between insulin glargine 100 units/mL and glycaemic control. Diabetes Obes Metab. 2019;21(6):1305-1310. doi:10.1111/dom.13653 [PubMed 30724009]Wexler DJ. Initial management of hyperglycemia in adults with type 2 diabetes mellitus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 15, 2022a.Wexler DJ. Insulin therapy in type 2 diabetes mellitus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 15, 2022b.Whitmore TJ, Trengove NJ, Graham DF, Hartmann PE. Analysis of insulin in human breast milk in mothers with type 1 and type 2 diabetes mellitus. Int J Endocrinol. 2012;2012:296368. [PubMed 22500167]Youssef D, El Abbassi A, Woodby G, Peiris AN. Benefits of twice-daily injection with insulin glargine: a case report and review of the literature. Tenn Med. 2010;103(2):42-43. [PubMed 20345066]Zeitler P, Arslanian S, Fu J, Pinhas-Hamiel O, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Type 2 diabetes mellitus in youth. Pediatr Diabetes. 2018;19(suppl 27):28-46. doi:10.1111/pedi.12719 [PubMed 29999228]Topic 9023 Version 361.0

CloseTranexamic acid: Drug informationTranexamic acid: Drug information(For additional information see "Tranexamic acid: Patient drug information" and see "Tranexamic acid: Pediatric drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USCyklokapron;LystedaBrand Names: CanadaCyklokapron;Erfa-Tranexamic;GD-Tranexamic Acid;MAR-Tranexamic AcidPharmacologic CategoryAntifibrinolytic Agent;Antihemophilic Agent;Hemostatic Agent;Lysine AnalogDosing: AdultThe adult dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editor: Edith A Nutescu, PharmD, MS, FCCP.Note: Safety: Higher total IV doses (eg, ≥50 mg/kg), such as those given perioperatively, may be associated with an increased risk of seizures; lower doses (eg, 1 or 2 g given in the first 8 hours of trauma) do not appear to increase the risk of seizure or venous thromboembolism (Ref).Abnormal uterine bleeding, nonacuteAbnormal uterine bleeding, nonacute (alternative agent): Note: Alternative for patients who decline or should not use hormonal therapy. Start at onset of heavy menstrual bleeding.Oral:Lysteda: 1.3 g 3 times daily for up to 5 days during monthly menstruation.Cyklokapron [Canadian product]: 1 to 1.5 g 3 to 4 times daily for up to 5 days during menstruation (Ref).Dental procedures in patients on oral anticoagulant therapyDental procedures in patients on oral anticoagulant therapy (off-label use):Oral rinse: 5% solution (extemporaneously prepared): Administer 5 to 10 minutes prior to the procedure; hold 5 to 10 mL in mouth and rinse for 2 minutes; drain gently, being careful not to forcibly spit and dislodge clots; do not eat or drink for 1 hour after using oral rinse. Repeat 3 to 4 times daily for 1 to 2 days after the procedure (Ref).Hemoptysis, treatmentHemoptysis (nonmassive), treatment (off-label use):Inhalation for nebulization: 500 mg (using injectable solution) 3 times daily for up to 5 days (Ref).Hereditary angioedema, long-term prophylaxisHereditary angioedema, long-term prophylaxis (alternative agent) (off-label use):Note: May be used when other agents (eg, C1 inhibitor, human monoclonal antibody) are not available or contraindicated (Ref).Oral: Initial: 500 to 650 mg two to three times daily; titrate gradually based on response and tolerability; usual daily dose: 3 g/day (Ref).Hereditary hemorrhagic telangiectasia, epistaxis or other bleeding sitesHereditary hemorrhagic telangiectasia, epistaxis or other bleeding sites (alternative agent) (off-label use): Note: May be used in carefully selected patients in whom local therapy and other management options are insufficient.Oral: Initial: 1.5 g twice daily or 1 g three times daily for 4 to 10 days; adjust dose as needed based on response and tolerability to a usual daily dose of 2 to 4.5 g in 2 or 3 divided doses (Ref).Intracranial hemorrhage associated with thrombolytic treatmentIntracranial hemorrhage associated with thrombolytic treatment (alternative agent) (off-label use): Note: Consider for use in addition to cryoprecipitate or when cryoprecipitate is contraindicated in patients who have a symptomatic intracranial hemorrhage after receiving thrombolytic within the past 24 hours (Ref).IV: 1 g (or 10 to 15 mg/kg) once; administer at a rate not to exceed 100 mg/minute (generally over 10 to 20 minutes) (Ref).Perioperative prevention of blood loss and transfusionPerioperative prevention of blood loss and transfusion (eg, cardiac surgery, other surgeries with significant blood loss):Note: There is wide variety in doses and routes of administration (IV, oral, and/or topical). Dosing and timing of administration are procedure and institution specific. Recommendations provided below are examples of IV regimens for use in selected surgeries; refer to institutional protocols.Usual dose and range: IV: 1 g (or 10 to 30 mg/kg) prior to procedure; administer at a rate not to exceed 100 mg/minute (generally over 10 to 30 minutes). Depending upon type of procedure, a continuous infusion may be given intraoperatively after the initial bolus dose, or the bolus dose may be repeated at the end of procedure and/or during the postoperative period (Ref).Cardiac surgery (off-label use):Note: Optimal regimen is uncertain; refer to institutional protocol.IV: Loading dose: 10 to 30 mg/kg administered at a rate not to exceed 100 mg/minute (generally over 10 to 20 minutes), followed by 1 to 16 mg/kg/hour (Ref). Alternatively, some centers administer a single loading dose of 50 mg/kg (Ref).Orthopedic surgery (hip or knee arthroplasty) (off-label use):Note: Optimal regimen is uncertain; refer to institutional protocol. Use in patients without a baseline high risk of thromboembolism. For patients with risk factors for thromboembolism, consider risk of thromboembolism vs benefit of reduced blood loss (Ref).IV: 1 g (or 10 to 15 mg/kg) administered before skin incision at a rate not to exceed 100 mg/minute (generally over 10 to 20 minutes); repeat dose at skin closure or up to 12 hours later; some experts recommend a third dose during the postoperative period if needed (Ref). Note: Some experts use intra-articular tranexamic acid (ie, 1 g per 50 mL of NS applied topically into the wound at the end of the procedure) (Ref).Spinal surgery (eg, spinal fusion) (off-label use):Note: Optimal regimen is uncertain; refer to institutional protocol.IV: 10 to 15 mg/kg administered prior to incision at a rate not to exceed 100 mg/minute (generally over 10 to 20 minutes), followed by 1 to 2 mg/kg/hour as a continuous infusion for the remainder of the surgery; discontinue at the end of the procedure (Ref).Postpartum hemorrhage, preventionPostpartum hemorrhage, prevention (adjunctive agent) (off-label use): Note: For use in patients in high bleeding risk situations in conjunction with standard prophylactic uterotonics (eg, oxytocin) (Ref).IV: 1 g (or 10 to 15 mg/kg) over 10 to 20 minutes (Ferrari 2022; Saccone 2019); may administer before skin incision for cesarean deliveries and after cord clamping for vagin*l deliveries (Ref).Postpartum hemorrhage, treatmentPostpartum hemorrhage, treatment (adjunctive agent) (off-label use): Note: For continued bleeding despite oxytocin; used in conjunction with other therapies/procedures.IV: 1 g over 10 to 20 minutes given within 3 hours of vagin*l birth or cesarean delivery. If bleeding continues after 30 minutes, may repeat the dose in conjunction with thorough re-evaluation for cause of continued or recurrent bleeding (Ref).Tooth extraction in patients with hemostatic defectsTooth extraction in patients with hemostatic defects (eg, hemophilia, von Willebrand disease, other factor deficiencies associated with bleeding) (adjunctive agent):Note: Generally used in conjunction with (and not as a substitute for) replacement of the appropriate clotting factor, especially in individuals with hemophilia. Do not give simultaneously with an activated prothrombin complex concentrate, as this can increase the risk of thromboembolism; if used concurrently, separate by ≥12 hours (Ref). Consultation with a hemophilia treatment center is advised.IV: 10 mg/kg using actual body weight (usual dose range: 500 mg to 1 g) administered ~2 hours before procedure at a rate not to exceed 100 mg/minute (generally over 10 to 20 minutes), then 10 mg/kg 3 to 4 times daily for 2 to 8 days. Alternatively, 10 mg/kg as a single dose ~2 hours prior to procedure; following procedure, transition to oral tranexamic acid depending on individual patient characteristics, type of procedure, other therapies, and degree of bleeding (Ref).Oral: 25 mg/kg (usual dose range: 1 to 1.5 g) given 2 hours prior to procedure, then 25 mg/kg (usual dose range: 1 to 1.5 g) 3 to 4 times daily for up to 7 to 10 days (Ref).Trauma-associated hemorrhage or traumatic brain injuryTrauma-associated hemorrhage or traumatic brain injury (off-label use):Note: Consider for use in patients with significant hemorrhage, at risk of significant hemorrhage, or in moderate traumatic brain injury (TBI) (Glasgow Coma Scale [GCS] score >8 and <13); patients with severe TBI (GCS score 3 to 8) may not demonstrate benefit (Ref).IV: Loading dose: 1 g over 10 minutes started within 3 hours of injury, followed by 1 g over the next 8 hours as a continuous infusion. Note: Some experts suggest using thromboelastogram or rotational thromboelastometry to guide therapy (Ref).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultThe renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.Note: Tranexamic acid is >95% eliminated by the kidney. Dosing recommendations may vary by institution; also consult institutional protocols. No dosage adjustment necessary for indications requiring only 1 to 2 doses (Ref). Tranexamic acid oral rinses have limited absorption (Ref); therefore, the need for renal dose adjustment is unlikely when used for a limited period of time (Ref). There are no data on bioavailability of tranexamic acid administered via nebulization; renal dose adjustment recommendations cannot be provided; use with caution (Ref).Altered kidney function:IV:Intermittent injection (Ref): Note: The following adjustments are based on a usual recommended dose of 10 mg/kg or 1 g 3 to 4 times daily.Serum creatinine <1.4 mg/dL (<120 micromol/L): No dosage adjustment necessary.Serum creatinine ≥1.4 to <2.8 mg/dL (≥120 micromol/L to <250 micromol/L): Administer usual dose twice daily.Serum creatinine ≥2.8 to <5.7 mg/dL (≥250 to <500 micromol/L): Administer usual dose once daily.Serum creatinine ≥5.7 mg/dL (≥500 micromol/L): Administer usual dose every 48 hours or 50% of the usual dose once daily.Continuous infusion:General recommendations (Ref): Note: Developed using the principal that % to be administered is (actual GFR divided by normal GFR) × 100%, with normal GFR = 90 mL/minute/1.73 m2. Recommendations should only be considered for cardiac or spinal indications; not applicable to trauma patients (Ref).Maintenance infusion following loading dose:eGFR ≥90 mL/minute/1.73 m2: Administer 100% of the usual maintenance rate.eGFR 60 to <90 mL/minute/1.73 m2: Administer 66% to 100% of the usual maintenance rate.eGFR ≥30 to <60 mL/minute/1.73 m2: Administer 33% to 66% of the usual maintenance rate.eGFR <30 mL/minute/1.73 m2: Administer 17% to 33% of the usual maintenance rate.Cardiac surgery regimen-specific examples: Note: These are examples of published regimens utilizing a continuous infusion; optimal regimen is uncertain; also refer to institutional protocol.eGFR-based regimen (BART regimen) (Ref): eGFR ≥90 mL/minute/1.73 m2: Loading dose: 30 mg/kg followed by 16 mg/kg/hour.eGFR 60 to <90 mL/minute/1.73 m2: Loading dose: 30 mg/kg followed by 11 to 16 mg/kg/hour.eGFR >30 to <60 mL/minute/1.73 m2: Loading dose: 25 to 30 mg/kg followed by 5 to 10 mg/kg/hour.eGFR ≤30 mL/minute/1.73 m2: Loading dose: 25 to 30 mg/kg followed by 3 to 5 mg/kg/hour.Serum creatinine-based regimen (Ref):Serum creatinine 1.6 to 3.3 mg/dL: Reduce maintenance infusion to 1.5 mg/kg/hour (based on a 25% reduction from 2 mg/kg/hour).Serum creatinine 3.3 to 6.6 mg/dL: Reduce maintenance infusion to 1 mg/kg/hour (based on a 50% reduction from 2 mg/kg/hour).Serum creatinine >6.6 mg/dL: Reduce maintenance infusion to 0.5 mg/kg/hour (based on a 75% reduction from 2 mg/kg/hour).Oral (Ref): Note: The following adjustments are based on a usual recommended dose of 10 to 15 mg/kg or 1 to 1.5 g 3 to 4 times daily.Serum creatinine <1.4 mg/dL (<120 micromol/L): No dosage adjustment necessary.Serum creatinine ≥1.4 to <2.8 mg/dL (≥120 to <250 micromol/L): Administer usual dose twice daily.Serum creatinine ≥2.8 to <5.7 mg/dL (≥250 to <500 micromol/L): Administer usual dose once daily.Serum creatinine ≥5.7 mg/dL (≥500 micromol/L): Administer usual dose every 48 hours, or 50% of the usual dose every 24 hours.Hemodialysis, intermittent (thrice weekly): Likely to be dialyzable (low protein binding, low Vd (Ref)): Note: Because tranexamic acid is dialyzable, schedule intermittent doses after hemodialysis when possible.IV (intermittent injection), Oral: Administer usual dose every 48 hours, or 50% of the usual dose every 24 hours (Ref).IV (continuous infusion): Dose as for eGFR <30 mL/minute/1.73 m2 (Ref).Peritoneal dialysis: Likely to be dialyzable (low protein binding, low Vd (Ref)).IV (intermittent injection), Oral: Administer usual dose every 48 hours, or 50% of the usual dose every 24 hours (Ref).IV (continuous infusion): Dose as for eGFR <30 mL/minute/1.73 m2 (Ref).CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Close monitoring of response and adverse reactions (eg, seizures, thrombotic events) due to drug accumulation is important.IV (intermittent injection), Oral: Administer usual dose twice daily (Ref).IV (continuous infusion): Dose as for eGFR 30 to 60 mL/minute/1.73 m2 (Ref).PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and adverse reactions (eg, seizures, thrombotic events) due to drug accumulation is important.IV (intermittent injection), Oral: Administer usual dose twice daily (Ref).IV (continuous infusion): Dose as for eGFR 30 to 60 mL/minute/1.73 m2 (Ref).Dosing: Hepatic Impairment: AdultNo dosage adjustment is necessary.Dosing: Pediatric(For additional information see "Tranexamic acid: Pediatric drug information")Diffuse alveolar hemorrhage, treatmentDiffuse alveolar hemorrhage (intractable), treatment: Very limited data available (Ref), ideal dose-response not established:Children ≤25 kg: Inhaled: 250 mg every 6 hours for 3 to 4 doses (18 to 24 hours); if response occurs, continue treatment for another 2 to 3 doses after bleeding completely stops; if no or minimal response or bleeding worsens, add inhaled recombinant factor VIIa; maximum duration of inhaled therapy: 3 days.Children >25 kg and Adolescents: Inhaled: 500 mg inhaled every 6 hours for 3 to 4 doses (18 to 24 hours); if response occurs, continue treatment for another 2 to 3 doses after bleeding completely stops; if no or minimal response or bleeding worsens, add inhaled recombinant factor VIIa; maximum duration of inhaled therapy: 3 days.Dosing based on a prospective pilot study of 18 children (median age: 24 months [interquartile range: 11.3 to 58.5 months]) with intractable diffuse alveolar hemorrhage (DAH) who received inhaled tranexamic acid; DAH responded to inhaled tranexamic treatment alone in 10 children (56%); the 8 nonresponders had inhaled recombinant factor VIIa added; 75% (n=6) of these patients had complete cessation of DAH; none of the patients who responded to treatment had recurrence or complications reported (Ref). Two retrospective studies have reported doses of 250 to 500 mg every 6 to 12 hours until resolution of bleeding for pulmonary hemorrhages (Ref).Hereditary angioedema, prophylaxisHereditary angioedema (HAE), prophylaxis: Limited data available:Long-term prophylaxis: Note: Not the preferred treatment option; reserve use for when C1-inhibitor concentrate is unavailable (Ref).Children and Adolescents: Oral: 20 to 50 mg/kg/day in 2 to 3 divided doses; doses up to 75 mg/kg/day have been reported; maximum daily dose range: 3,000 to 6,000 mg/day (Ref); may consider alternate-day regimen or twice-weekly regimen when frequency of attacks reduces (Ref).Short-term prophylaxis (eg, prior to surgical or diagnostic interventions in head/neck region): Note: Not the preferred treatment option; some experts do not recommend use for short-term prophylaxis (Ref).Weight directed: Children and Adolescents: Oral: 20 to 50 mg/kg/day in 2 to 3 divided doses; maximum daily dose range: 3,000 to 6,000 mg/day; initiate therapy at least 5 days before and continue for 2 days postprocedure (Ref).Fixed dosing: Children and Adolescents: Patients with an adequate weight (eg, ≥50 kg): Oral: 500 mg 4 times daily (Ref); therapy usually initiated 2 to 5 days before dental work and continue for 2 days after the procedure (Ref).Menstrual bleeding, heavyMenstrual bleeding, heavy: Postmenarche female: Tablet (Lysteda): Oral: 1,300 mg 3 times daily for up to 5 days during monthly menstruation; maximum daily dose: 3,900 mg/day.Prevention of bleeding associated with tooth extraction in hemophilic patientsPrevention of bleeding associated with tooth extraction in hemophilic patients: Note: Use in combination with replacement therapy.Infants, Children, and Adolescents: IV: 10 mg/kg immediately before surgery, then 10 mg/kg/dose 3 to 4 times daily for 2 to 8 days.Prevention of perioperative bleedingPrevention of perioperative bleeding: Limited data available; reported regimens variable and ideal dose-response not established:General dosing (non-cardiac): Infants, Children, and Adolescents: IV: Loading dose: 10 to 30 mg/kg followed by a continuous IV infusion at 5 to 10 mg/kg/hour; dosing based on a pharmaco*kinetic model to achieve a target serum concentration of 20 mcg/mL and 70 mcg/mL, respectively (Ref).Cardiac surgery with cardiopulmonary bypass: Infants, Children, and Adolescents:Low dose: IV: Loading dose: 10 mg/kg followed by a continuous IV infusion at 5 mg/kg/hour; dosing based on a pharmaco*kinetic model to achieve a target serum concentration of 20 mcg/mL; tranexamic acid must also be added to cardiopulmonary bypass solution at a concentration of 20 mcg/mL (Ref). A pharmaco*kinetic analysis (n=43; mean age: 123 days [range: 6 to 348 days]; mean weight: 4.95 kg [range: 2.3 to 9.5 kg]) targeting a serum concentration of 20 mcg/mL proposed the following regimen: Loading dose: 10 mg/kg, followed by a continuous IV infusion at 10 mg/kg/hour until initiation of cardiopulmonary bypass, then IV priming bolus: 4 mg/kg into the bypass prime volume, followed by a continuous IV infusion at 4 mg/kg/hour (Ref). Another regimen studied in 2 trials (n=80; age range: 2 months to 15 years) is 10 mg/kg into the bypass circuit after induction, during cardiopulmonary bypass, and after protamine reversal of heparin for a total of 3 doses (Ref). A pharmaco*kinetic analysis has proposed the following regimen to achieve a target serum concentration range of 20 to 30 mcg/mL in children 1 to 12 years and weighing 5 to 40 kg: IV: Loading dose: 6.4 mg/kg over 5 minutes followed by a weight-adjusted continuous IV infusion in the range of 2 to 3.1 mg/kg/hour; the pharmaco*kinetic data showed that patients weighing less should receive an initial continuous IV infusion rate at the higher end of the range (ie, if patient weight=5 kg then initial continuous IV infusion rate: 3.1 mg/kg/hour; if patient weight=40 kg then initial continuous IV infusion rate: 2 mg/kg/hour) (Ref).Intermediate dose: IV: Loading dose: 30 mg/kg followed by a continuous IV infusion at 10 mg/kg/hour; dosing based on a pharmaco*kinetic model to achieve a target serum concentration of 70 mcg/mL; tranexamic acid must also be added to cardiopulmonary bypass solution at a concentration of 70 mcg/mL (Ref).High dose: IV: Loading dose: 50 mg/kg, followed by a continuous IV infusion at 15 mg/kg/hour and 50 mg/kg priming dose into the circuit when bypass initiated (Ref); dosing based on a pharmaco*kinetic model to achieve a target serum concentration of 150 mcg/mL (Ref).Spinal surgery (eg, idiopathic scoliosis): Children ≥8 years and Adolescents: IV: Loading dose: 100 mg/kg, followed by a continuous IV infusion at 10 mg/kg/hour until skin closure (Ref). Other reported regimens with positive results: Loading dose: 20 mg/kg, followed by a continuous IV infusion at 10 mg/kg/hour (Ref); loading dose: 10 mg/kg, followed by a continuous IV infusion at 1 mg/kg/hour (Ref); loading dose: 50 mg/kg, followed by a continuous IV infusion at 5 mg/kg/hour (Ref).Craniosyntosis surgery: Infants ≥2 months and Children ≤6 years: IV: Loading dose: 50 mg/kg over 15 minutes prior to incision, followed by a continuous IV infusion at 5 mg/kg/hour until skin closure (Ref) or loading dose: 15 mg/kg over 15 minutes prior to incision, followed by a continuous IV infusion at 10 mg/kg/hour until skin closure (Ref). Other reported regimens with positive results: Loading dose: 10 mg/kg at start of surgery, followed by a continuous IV infusion at 5 mg/kg/hour for 24 hours postoperatively (Ref).Trauma, hemorrhagicTrauma, hemorrhagic (acute traumatic coagulopathy): Limited data available: Note: Reported regimens are variable and ideal dose-response is not established:Children <12 years: IV: Loading dose: 15 mg/kg over 10 minutes given within 3 hours of injury (maximum dose: 1,000 mg/dose), followed by continuous IV infusion at 2 mg/kg/hour for ≥8 hours or until bleeding stops (Ref).Children ≥12 years and Adolescents: IV: Loading dose: 1,000 mg over 10 minutes given within 3 hours of injury, followed by 1,000 mg infused over 8 hours (Ref).Traumatic hyphemaTraumatic hyphema: Limited data available: Children and Adolescents: Oral: 25 mg/kg/dose every 8 hours for 5 to 7 days (Ref). Note: This same regimen may also be used for secondary hemorrhage after an initial traumatic hyphema event.Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricNote: Recommendations are dependent on use and route.Oral:Menorrhagia: Female Children ≥12 years and Adolescents:Scr >1.4 to ≤2.8 mg/dL: 1,300 mg twice daily for up to 5 days during monthly menstruation.Scr >2.8 to ≤5.7 mg/dL: 1,300 mg once daily for up to 5 days during monthly menstruation.Scr >5.7 mg/dL: 650 mg once daily for up to 5 days during monthly menstruation.Prophylaxis of hereditary angioedema: Children and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, due to risk of accumulation with kidney impairment, dosage adjustments are recommended (Ref).IV:Tooth extraction in patients with hemophilia: Infants, Children, and Adolescents:Scr 1.36 to ≤2.83 mg/dL: Maintenance dose of 10 mg/kg/dose twice daily.Scr >2.83 to ≤5.66 mg/dL: Maintenance dose of 10 mg/kg/dose once daily.Scr >5.66 mg/dL: Maintenance dose of 10 mg/kg/dose every 48 hours or 5 mg/kg/dose every 24 hours.Prophylaxis or treatment of mild to major bleeding secondary to trauma or surgery: Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, due to risk of accumulation with kidney impairment, dosage adjustments are recommended (Ref).Dosing: Hepatic Impairment: PediatricInfants, Children, and Adolescents: No adjustment is necessary.Dosing: Older AdultRefer to adult dosing.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution, Intravenous: Generic: 1000 mg/10 mL (10 mL)Solution, Intravenous [preservative free]: Cyklokapron: 1000 mg/10 mL (10 mL)Generic: 1000 mg/10 mL (10 mL); 1000 mg/100 mL in NaCl 0.7% (100 mL)Tablet, Oral: Lysteda: 650 mgGeneric: 650 mgGeneric Equivalent Available: USYesDosage Forms: CanadaExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Solution, Intravenous: Cyklokapron: 100 mg/mL (5 mL, 10 mL)Generic: 100 mg/mL (5 mL, 10 mL, 50 mL); 1000 mg/10 mL (10 mL)Tablet, Oral: Cyklokapron: 500 mgGeneric: 500 mgAdministration: AdultInhalation via nebulization (off-label use/route): Administer over 15 minutes via jet nebulizer (Ref).Injection: For indications requiring a loading dose (eg, trauma-associated hemorrhage, perioperative prevention of blood loss and transfusion), may administer undiluted by IV injection at a maximum rate of 100 mg/minute (Ref); faster rates may cause hypotension. For continuous IV infusions, dilute with compatible solutions and administer at a rate not to exceed 100 mg/minute.When used for the prevention of postpartum hemorrhage (off-label use), tranexamic acid can be infused before skin incision (cesarean deliveries) or after cord clamping (cesarean or vagin*l deliveries) (Ref).Oral: Administer without regard to meals. Swallow tablet whole; do not break, chew, or crush.Administration: PediatricOral: Administer without regard to meals; tablets should be swallowed whole; do not break, split, chew, or crush.Parenteral:Intermittent IV dose: May be administered undiluted by direct IV injection at a maximum rate of 100 mg/minute; faster rates may cause hypotension.Continuous IV infusion:Loading dose: May be administered either undiluted or diluted in a compatible diluent; infuse over 5 to 15 minutes (Ref). Neonatal patients received loading doses over 60 minutes (Ref).IV infusion: Following dilution, administer by continuous IV infusion at a rate not to exceed 100 mg/minute.Inhalation: Administer undiluted (100 mg/mL) by jet nebulization (Ref); time for nebulization average 15 minutes in adults (Ref).Use: Labeled IndicationsAbnormal uterine bleeding, nonacute (oral): Treatment of cyclic heavy menstrual bleeding.Limitations of use: For use in patients who may become pregnant; not for use prior to menarche or post menopause.Tooth extraction in patients with hemostatic defects (injection, oral [Cyklokapron; Canadian product]): Short-term use in hemophilia patients to reduce or prevent hemorrhage and reduce need for replacement therapy during and following tooth extraction.Use: Off-Label: AdultDental procedures in patients on oral anticoagulant therapy; Hemoptysis (nonmassive), treatment; Hereditary angioedema, long-term prophylaxis; Hereditary hemorrhagic telangiectasia, epistaxis or other bleeding sites; Intracranial hemorrhage associated with thrombolytic treatment; Perioperative prevention of blood loss and transfusion, cardiac surgery; Perioperative prevention of blood loss and transfusion, orthopedic surgery (hip or knee arthroplasty); Perioperative prevention of blood loss and transfusion, spinal surgery; Postpartum hemorrhage, prevention; Postpartum hemorrhage, treatment; Trauma-associated hemorrhage or traumatic brain injuryMedication Safety IssuesSound-alike/look-alike issues:Cyklokapron may be confused with cycloSPORINETXA (occasional abbreviation for tranexamic acid) is an error-prone abbreviation (mistaken as TNK an error-prone abbreviation for tenecteplase and tPA an error-prone abbreviation for alteplase)Administration issues:Inadvertent administration of tranexamic acid by the epidural or spinal route during neuraxial (eg, epidural, spinal) anesthesia has led to potentially fatal neurotoxic adverse reactions. Carefully evaluate storage procedures within the surgical suite, including separating tranexamic acid from local anesthetics; consider additional prevention measures, including purchasing, dispensing, and administration (ISMP [Smetzer] 2019; NAN Alert 2020; Patel 2019).Adverse Reactions (Significant): ConsiderationsHypersensitivity reactions (immediate and delayed)Immediate hypersensitivity reactions (eg, anaphylaxis) have been reported, ranging from mild pruritus and/or urticaria to more severe reactions, including angioedema, wheezing, hypotension, and anaphylactic shock (Ref). Delayed hypersensitivity reactions include fixed drug eruption and toxic epidermal necrolysis (TEN) (Ref).Mechanism: Immediate hypersensitivity reactions (eg, anaphylaxis, urticaria): Non–dose-related, immunologic, IgE-mediated. Delayed hypersensitivity reactions: Non–dose-related, immunologic, T-cell mediated (Ref).Onset: Immediate hypersensitivity reactions: Rapid; occur within 1 hour of administration but may occur up to 6 hours after exposure (Ref). Delayed hypersensitivity reactions: Varied; serious cutaneous adverse reactions, including TEN, occur 1 to 8 weeks after initiation (Ref).Ocular effectsVisual defects (eg, vision color changes, visual impairment, vision loss), retinal artery occlusion, and retinal venous occlusion have been reported (Ref). Conjunctivitis (ligneous), a form of membranous conjunctivitis, has been reported with the oral formulation but resolved upon discontinuation of therapy (Ref).Mechanism: Visual defects: Unknown (Ref). Ligneous conjunctivitis: Unknown; likely vasculopathy with increased vessel permeability and consequent loss of protein (Ref). Onset: Visual defects: Varied; retinal artery occlusion occurred 5 days to 1 month after initiation (Ref). Ligneous conjunctivitis: Varied; occurred 1 to 9 months after initiation; upon reintroduction, occurred within 2 days (Ref).Risk factors:• Kidney failure (Ref)Seizures and myoclonusSeizures have been reported, typically generalized tonic-clonic; although, focal and mixed seizures may also occur (Ref). Myoclonus is noted in ~20% of patients. Seizures usually persist for a few minutes and rarely progress to status epilepticus (Ref). Recurrent seizures may occur in 30% to 60% of patients during the first 24 to 48 hours after postoperative administration (Ref). The incidence of seizures is ~2.7% (Ref).Mechanism: Dose-related: Unknown; may occur due to antagonistic effect of tranexamic acid at GABA-A receptors and neural glycine receptors, resulting in lowered seizure threshold; cerebral emboli may also play a role (Ref).Onset: Rapid; within the first 5 to 8 hours after postoperative administration (Ref). Risk factors:• Higher intravenous doses may increase risk (Ref); although, one study showed no increased risk of seizure with high dose versus low dose (Ref)• Cardiac surgery, in particular patients undergoing open heart surgery; deep hypothermic circulatory arrest, increased cardiopulmonary bypass time, or prolonged aortic cross-clamp time are also associated with increased risk in this population (Ref)• Females (Ref)• Increased age (>70 years) (Ref)• Poor overall health (Ref)• Kidney impairment (Ref)• Prior neurological and cardiovascular disorders (Ref)• History of stroke (Ref)Thromboembolic eventsVenous thromboembolism and arterial thromboembolism, including deep vein thrombosis, pulmonary embolism, retinal vein occlusion, and retinal artery occlusion, have been reported (Ref). The incidence of thromboembolism after various surgical procedures has been reported from 0.3% to 8.2% (Ref). In contrast, some studies have shown no significant increase in thromboembolism risk (Ref).Mechanism: Dose-related; unknown; reversibly displaces plasminogen from fibrin, resulting in the cessation of fibrinolysis (Ref). May also inhibit the proteolytic activity of plasmin (Ref).Onset: Varied; may occur within 1 hour (Ref), up to several years after initiation (Ref).Risk factors: • High doses (≥20 mg/kg) or 2 to 4 g (Ref)• Variceal bleeding or liver disease (Ref)• Increased age (Ref)• Cardiovascular disease (Ref)• History of or active thromboembolic disease• Concurrent procoagulant agents (eg, prothrombin complex concentrate, oral tretinoin, hormonal contraceptives)Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. As reported with oral formulation unless otherwise noted.>10%:Gastrointestinal: Abdominal pain (20%)Nervous system: Headache (50%)Neuromuscular & skeletal: Back pain (21%), musculoskeletal pain (11%)Respiratory: Nasal signs and symptoms (25%; including sinus symptoms)1% to 10%:Hematologic & oncologic: Anemia (6%)Nervous system: Fatigue (5%)Neuromuscular & skeletal: Arthralgia (7%), muscle cramps (≤7%), muscle spasm (≤7%)Postmarketing (all formulations):Cardiovascular: Arterial thromboembolism (Meaidi 2021), deep vein thrombosis (HALT-IT 2020), hypotension (with rapid IV injection), pulmonary embolism (HALT-IT 2020; Ijaopo 2020), venous thromboembolism (HALT-IT 2020)Dermatologic: Allergic dermatitis (Imbesi 2010), fixed drug eruption (Kaku 2014), pruritus (Imbesi 2010), toxic epidermal necrolysis (Pretel Irazabal 2013), urticaria (Imbesi 2010)Gastrointestinal: Diarrhea, nausea, vomitingHypersensitivity: Anaphylactic shock, anaphylaxis (El Hanache 2021), angioedema (Imbesi 2010), nonimmune anaphylaxisNervous system: Cerebral thrombosis, dizziness, myoclonus (Lecker 2016), seizure (Lecker 2016)Ophthalmic: Chromatopsia, conjunctivitis (ligneous) (Song 2014), retinal artery occlusion (Wijetilleka 2017), retinal vein occlusion, vision color changes (Kiser 2021), vision loss (Wijetilleka 2017), visual impairment (Kitamura 2003)Renal: Renal cortical necrosis (Ko 2017)Respiratory: Wheezing (Murdaca 2020)ContraindicationsHypersensitivity to tranexamic acid or any component of the formulation.Injection: Active intravascular clotting; subarachnoid hemorrhage.Oral: Active thromboembolic disease (eg, cerebral thrombosis, DVT, or pulmonary embolism); history of thrombosis or thromboembolism, including retinal vein or retinal artery occlusion; intrinsic risk of thrombosis or thromboembolism (eg, hypercoagulopathy, thrombogenic cardiac rhythm disease, thrombogenic valvular disease); patients using combined hormonal contraception who may become pregnant.Canadian labeling: Additional contraindications (not in the US labeling): Injection, oral: History or risk of thrombosis (unless concurrent anticoagulation therapy is possible); hematuria; epidural administration; intrathecal administration.Warnings/PrecautionsConcerns related to adverse effects:• CNS effects: May cause dizziness, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).Disease-related concerns:• Disseminated intravascular coagulation: Use with extreme caution in patients with disseminated intravascular coagulation requiring antifibrinolytic therapy; patients should be under strict supervision of a health care provider experienced in treating this disorder.• Renal impairment: Use with caution in patients with renal impairment; dosage modification necessary.• Subarachnoid hemorrhage: Use with caution in patients with subarachnoid hemorrhage; cerebral edema and infarction may occur.• Vascular disease: Use with caution in patients with uncorrected cardiovascular or cerebrovascular disease due to the complications of thrombosis.Metabolism/Transport EffectsNone known.Drug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Anti-inhibitor Coagulant Complex (Human): Antifibrinolytic Agents may enhance the thrombogenic effect of Anti-inhibitor Coagulant Complex (Human).Risk X: Avoid combinationEstrogen Derivatives: May enhance the thrombogenic effect of Tranexamic Acid. Risk X: Avoid combinationFactor IX Complex (Human) [(Factors II, IX, X)]: Antifibrinolytic Agents may enhance the adverse/toxic effect of Factor IX Complex (Human) [(Factors II, IX, X)]. Specifically, the risk for thrombosis may be increased.Risk X: Avoid combinationHormonal Contraceptives: May enhance the thrombogenic effect of Tranexamic Acid. Risk X: Avoid combinationProthrombin Complex Concentrate (Human) [(Factors II, VII, IX, X), Protein C, and Protein S]: Antifibrinolytic Agents may enhance the adverse/toxic effect of Prothrombin Complex Concentrate (Human) [(Factors II, VII, IX, X), Protein C, and Protein S]. Specifically, the risk for thrombosis may be increased.Risk X: Avoid combinationThrombolytic Agents: Tranexamic Acid may diminish the therapeutic effect of Thrombolytic Agents. Thrombolytic Agents may diminish the therapeutic effect of Tranexamic Acid.Risk X: Avoid combinationTretinoin (Systemic): May enhance the thrombogenic effect of Antifibrinolytic Agents. Management: Concomitant use of antifibrinolytics and tretinoin is not recommended. If combined, monitor patients closely for any signs of thrombotic complications. Risk D: Consider therapy modificationReproductive ConsiderationsTranexamic acid is an alternative agent for the treatment of heavy menstrual bleeding and one option for patients who desire future fertility (ACOG 2019). The manufacturer recommends non-hormonal contraception during treatment, as hormonal contraceptives may increase the risk of thromboembolic events (use of hormonal contraception is contraindicated by some manufacturers). However, tranexamic acid in combination with oral contraceptives may be considered for the treatment of heavy menstrual bleeding when monotherapy is ineffective and other treatment options have failed (ACOG 2013; ACOG 2019).Pregnancy ConsiderationsTranexamic acid crosses the placenta; concentrations within cord blood are similar to maternal serum.Due to pregnancy-induced physiologic changes, some pharmaco*kinetic properties of oral tranexamic acid may be altered (Muhunthan 2020).Oral tranexamic acid is used off label for the long-term prophylaxis of hereditary angioedema (HAE) and use for this indication in pregnant patients has been reported (González-Quevedo 2016; Machado 2017; Milingos 2009). Tranexamic acid is not the preferred therapy for HAE in pregnant patients. Use may be considered for long-term prophylaxis of HAE during pregnancy when preferred treatment is not available; however, efficacy data are not available (US HAEA [Busse 2021]; WAO/EEACI [Maurer 2022]).IV tranexamic acid is used off label for the treatment of postpartum hemorrhage (PPH) (Ducloy-Bouthors 2011; RCOG [Pavord 2017]; WOMAN Trial Collaborators 2017). A significant reduction in risk of death due to bleeding was observed when treatment was started within 3 hours of vagin*l birth or cesarean section (WOMAN Trial Collaborators 2017). Tranexamic acid is recommended for the treatment of obstetric hemorrhage when initial medical management fails (ACOG 2017; WHO 2017).IV tranexamic acid has also been studied for prophylaxis of PPH in patients prior to vagin*l or cesarean delivery (Novikova 2015; Saccone 2019; Sentilhes 2018; Sentilhes 2021; Simonazzi 2016; Xia 2020). Tranexamic acid may be considered as adjunctive therapy in patients at high risk for PPH. Patients at high risk include those with a known coagulation defect; bleeding upon admission; hematocrit <30%; history of PPH; abnormal vital signs (hypotension and tachycardia); or placenta previa, accreta, increta, or percreta. However, available data related to prophylactic use are insufficient, and use for routine prophylaxis against PPH is not currently recommended outside of the context of clinical research (ACOG 2017; Muñoz 2019). Additional studies may be needed to define the optimal dose (Ahmadzia 2021; Li 2021).When managing PPH, do not use tranexamic acid in patients with clear contraindications to therapy, including active intravascular clotting, known thromboembolic event during pregnancy, known hemostatic disorders, or known hypersensitivity to tranexamic acid (Ducloy-Bouthors 2011; Shakur 2010; WHO 2017).Breastfeeding ConsiderationsTranexamic acid is present in breast milk.Breast milk concentrations of tranexamic acid in patients who were lactating were ~1% of the maximum maternal serum concentration when measured 1 hour after the last dose following 2 days of treatment (maternal dose and actual milk concentrations not provided) (Verstraete 1985).Thromboembolic disorders were not observed in breastfed infants following maternal use of tranexamic acid for the treatment of postpartum hemorrhage (WOMAN Trial Collaborators 2017). An increased risk of adverse events was not observed in 21 breastfed infants exposed to tranexamic acid following maternal use for coagulation disorders (maternal dose range: 1.5 to 4 g/day). Authors of this study suggest taking the maternal dose immediately after breastfeeding to minimize infant exposure and monitor the infant for adverse events (Gilad 2014).According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Tranexamic acid is not the preferred treatment for hereditary angioedema in patients who are breastfeeding (US HAEA [Busse 2021]; WAO/EEACI [Maurer 2022]).Monitoring ParametersOphthalmic examination (visual acuity, optical coherence tomography) at regular intervals if on long-term therapy (>3 months); signs/symptoms of hypersensitivity reactions, seizures (consider EEG monitoring for patients with history of seizures or who experience myoclonic movements, twitching, or evidence of focal seizures), and thrombotic events; in patients with trauma-associated hemorrhage, thromboelastography (TEG), or rotational thromboelastometry (ROTEM) where available (Colwell 2021).Mechanism of ActionForms a reversible complex that displaces plasminogen from fibrin resulting in inhibition of fibrinolysis; it also inhibits the proteolytic activity of plasminWith reduction in plasmin activity, tranexamic acid also reduces activation of complement and consumption of C1 esterase inhibitor (C1-INH), thereby decreasing inflammation associated with hereditary angioedema. Pharmaco*kineticsDistribution: Vd: IV: 9 to 12 L; cerebrospinal fluid and aqueous humor of eye concentrations are 10% of plasma.Protein binding: ~3%, primarily to plasminogen.Bioavailability: Oral: ~45%.Half-life elimination: IV: ~2 hours; Oral: ~11 hours.Time to peak: Oral:Single dose: Mean: 2.5 hours (range: 1 to 5 hours).Multiple dose: Mean: 2.5 hours (range: 2 to 3.5 hours).Excretion: Urine (>95% as unchanged drug).Pharmaco*kinetics: Additional ConsiderationsAltered kidney function: Following administration of a single IV injection, urinary excretion declines as renal function decreases.Pediatric: The Cmax and AUC values after a single oral dose of 1,300 mg in adolescent females were 20% to 25% less than those in adult females given the same dose.In vitro data suggests that neonates require a lower serum tranexamic acid concentration than adults (6.54 mcg/mL vs 17.5 mcg/mL) to completely prevent fibrinolysis (Yee 2013). In pediatric patients weighing 5 to 40 kg undergoing cardiac surgery with by-pass, a target serum concentration range of 20 to 30 mcg/mL has been used in pharmaco*kinetic analysis (Dowd 2002; Grassin-Delyle 2013).Pricing: USSolution (Cyklokapron Intravenous)1000 mg/10 mL (per mL): $2.40Solution (Tranexamic Acid Intravenous)1000 mg/10 mL (per mL): $0.46 - $8.68Solution (Tranexamic Acid-NaCl Intravenous)1000MG/100ML 0.7% (per mL): $0.25Tablets (Lysteda Oral)650 mg (per each): $6.52Tablets (Tranexamic Acid Oral)650 mg (per each): $5.21 - $5.22Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.Brand Names: InternationalAmchafibrin (ES);Anaxyl (BD);Aneptil (LK);Azeptil (TR);Bionex (BD);Blonda (TW);Caprilon (FI);Ciclokapron (VE);Cyclokapron (BE, CL, IS, LU, MT);Cyklokapron (AE, AT, AU, BB, BH, CH, CY, DE, DK, EE, ET, FI, GB, IE, IQ, IR, JO, KW, LB, LY, NL, NO, NZ, OM, QA, SA, SE, SG, SY, YE, ZA, ZW);Duhemos (VN);Espercil (CL);Exacyl (AE, BE, CZ, FR, HN, LB, LU, PL);Fimoplas (PH);Gemaxam (UA);Gemotran (UA);Hemanex (PH);Hemoblock (EC);Hemoclot (PH);Hemokapron (EG);Hemostan (PH);Hemotrex (PH);Hexakapron (IL);Kalnex (ID);Lunex (ID);Lysteda (CR, DO, GT, HN, NI, PA, SV);Medsamic (VN);Morwak (ZA);Nexa (ID);Nobleed (LK);Oilexam (DK);Pilexam (NO);Qualixamin (HK);Ranexid (PH);Relcon (TW);Rikaparin (TW);Ronex (ID);Sangera (UA);Tiren (MY);Tosano (HK);Tracid (BD);Tramic (TH);Tranarest (IN);Tranex (BD, EG, IT);Tranexam (RU);Tranexid (ID);Tranic (ZA);Tranlok (LK);Tranmix (VN);Transamin (BR, CN, HK, JP, KR, MY, PK, TH, VN);Transamina (UY);Transic (TH);Tranxa (ID);Traxan (PH);Trenaxin (PH);Trenolk (HR);Trexacont (BR);Zamic (AU);Zucerin (TW)For country code abbreviations (show table)Aboul-Fotouh S, Habib MZ, Magdy SM, Hassan BEE. Tranexamic acid-associated fatal status epilepticus in a paediatric non-cardiac surgery: a case report and literature review. Br J Clin Pharmacol. 2022;88(9):4211-4216. doi:10.1111/bcp [PubMed 35244235]Ahmadzia HK, Luban NLC, Li S, et al. Optimal use of intravenous tranexamic acid for hemorrhage prevention in pregnant women. Am J Obstet Gynecol. 2021;225(1):85.e1-85.e11. doi:10.1016/j.ajog.2020.11.035 [PubMed 33248975]Alshryda S, Mason J, Sarda P, et al. Topical (intra-articular) tranexamic acid reduces blood loss and transfusion rates following total hip replacement: a randomized controlled trial (TRANX-H). J Bone Joint Surg Am. 2013a;95(21):1969-1974. doi:10.2106/JBJS.L.00908 [PubMed 24196467]Alshryda S, Mason J, Vaghela M, et al. Topical (intra-articular) tranexamic acid reduces blood loss and transfusion rates following total knee replacement: a randomized controlled trial (TRANX-K). J Bone Joint Surg Am. 2013b;95(21):1961-1968. doi:10.2106/JBJS.L.00907 [PubMed 24196466]American College of Obstetricians and Gynecologists (ACOG). ACOG Committee Opinion No. 557: Management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women. Obstet Gynecol. 2013;121(4):891-896. doi:10.1097/01.AOG.0000428646.67925.9a [PubMed 23635706]American College of Obstetricians and Gynecologists (ACOG). ACOG Committee Opinion No. 785: Screening and management of bleeding disorders in adolescents with heavy menstrual bleeding. Obstet Gynecol. 2019;134(3):e71-e83. doi:10.1097/AOG.0000000000003411 [PubMed 31441825]American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins—Obstetrics. Practice Bulletin No. 183: Postpartum hemorrhage. Obstet Gynecol. 2017;130(4):e168-e186. doi:10.1097/AOG.0000000000002351 [PubMed 28937571]Amundson AW, Johnson RL. Anesthesia for total knee arthroplasty. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 25, 2022.Andersson L, Eriksson O, Hedlund PO, Kjellman H, Lindqvist B. Special considerations with regard to the dosage of tranexamic acid in patients with chronic renal diseases. Urol Res. 1978;6(2):83-88. doi:10.1007/BF00255578 [PubMed 664136]Based on expert opinion.Bafaqih H, Chehab M, Almohaimeed S, et al. Pilot trial of a novel two-step therapy protocol using nebulized tranexamic acid and recombinant factor VIIa in children with intractable diffuse alveolar hemorrhage. Ann Saudi Med. 2015;35(3):231‐239. [PubMed 26409798]Baskaran D, Rahman S, Salmasi Y, Froghi S, Berber O, George M. Effect of tranexamic acid use on blood loss and thromboembolic risk in hip fracture surgery: systematic review and meta-analysis. Hip Int. 2018;28(1):3-10. doi:10.5301/hipint.5000556 [PubMed 28983887]Bellón T. Mechanisms of severe cutaneous adverse reactions: recent advances. Drug Saf. 2019;42(8):973-992. doi:10.1007/s40264-019-00825-2 [PubMed 31020549]Beno S, Ackery AD, Callum J, Rizoli S. Tranexamic acid in pediatric trauma: why not?. Crit Care. 2014;18(4):313. [PubMed 25043066]Berghella V. Management of the third stage of labor after vagin*l delivery: drug therapy to minimize hemorrhage. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 23, 2021.Bernardo E, Anders M, Schmees L, Resendiz K. Inhaled tranexamic acid for pulmonary hemorrhage in critically ill pediatric patients. Critical Care Medicine. 2019;47(1):577. [PubMed 32166295]Bérubé C. Factor XI (eleven) deficiency. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 13, 2021.Borea G, Montebugnoli L, Capuzzi P, Magelli C. Tranexamic acid as a mouthwash in anticoagulant-treated patients undergoing oral surgery. An alternative method to discontinuing anticoagulant therapy. Oral Surg Oral Med Oral Pathol. 1993;75(1):29-31. doi:10.1016/0030-4220(93)90401-o [PubMed 8419869]Bowen T, Cicardi M, Farkas H, et al. Canadian 2003 international consensus algorithm for the diagnosis, therapy, and management of hereditary angioedema. J Allergy Clin Immunol. 2004;114(3):629‐637. [PubMed 15356569]Bowen T, Cicardi M, Farkas H, et al. 2010 international consensus algorithm for the diagnosis, therapy and management of hereditary angioedema. Allergy Asthma Clin Immunol. 2010;6(1):24. doi:10.1186/1710-1492-6-24 [PubMed 20667127]Brockow K, Przybilla B, Aberer W, et al. Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM). Allergo J Int. 2015;24(3):94-105. doi:10.1007/s40629-015-0052-6 [PubMed 26120552]Brown MJ. Anesthesia for elective spine surgery in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 23, 2021.Busse PJ, Christiansen SC, Riedl MA, et al. US HAEA Medical Advisory Board 2020 guidelines for the management of hereditary angioedema. J Allergy Clin Immunol Pract. 2021;9(1):132-150.e3. doi:10.1016/j.jaip.2020.08.046 [PubMed 32898710]Callum JL, Yeh CH, Petrosoniak A, et al. A regional massive hemorrhage protocol developed through a modified Delphi technique. CMAJ Open. 2019;7(3):E546-E561. doi:10.9778/cmajo.20190042 [PubMed 31484650]Carroll ND, Restrepo CS, Eastridge BJ, Stasik CN. Left atrial thrombi following tranexamic acid in a bleeding trauma patient-A word of caution. J Card Surg. 2018;33(2):83-85. doi:10.1111/jocs.13521 [PubMed 29385649]Carter G, Goss A. Tranexamic Acid Mouthwash -- A Prospective Randomized Study of a 2-Day Regimen vs 5-Day Regimen to Prevent Postoperative Bleeding in Anticoagulated Patients Requiring Dental Extractions. Int J Oral Maxillofac Surg. 2003;32(5):504-7. [PubMed 14759109]Chauhan S, Bisoi A, Kumar N, et al. Dose Comparison of Tranexamic Acid in Pediatric Cardiac Surgery. Asian Cardiovasc Thorac Ann. 2004a;12(2):121-124. [PubMed 15213077]Chauhan S, Das SN, Bisoi A, et al. Comparison of Epsilon Aminocaproic Acid and Tranexamic Acid in Pediatric Cardiac Surgery. J Cardiothorac Vasc Anesth. 2004b;18(2):141-143. [PubMed 15073700]Choi WS, Irwin MG, Samman N. The Effect of Tranexamic Acid on Blood Loss During Orthognathic Surgery: A Randomized Controlled Trial. J Oral Maxillofac Surg. 2009;67(1):125-133. [PubMed 19070758]Chornenki NLJ, Um KJ, Mendoza PA, et al. Risk of venous and arterial thrombosis in non-surgical patients receiving systemic tranexamic acid: a systematic review and meta-analysis. Thromb Res. 2019;179:81-86. doi:10.1016/j.thromres.2019.05.003 [PubMed 31100632]Chwajol M, Starke RM, Kim GH, Mayer SA, Connolly ES. Antifibrinolytic therapy to prevent early rebleeding after subarachnoid hemorrhage. Neurocrit Care. 2008;8(3):418-426. doi:10.1007/s12028-008-9088-5 [PubMed 18386187]Colwell C. Initial management of moderate to severe hemorrhage in the adult trauma patient. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 20, 2021.Connolly ES Jr, Rabinstein AA, Carhuapoma JR, et al; American Heart Association Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Clinical Cardiology. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012;43(6):1711-1737. doi:10.1161/STR.0b013e3182587839 [PubMed 22556195]Couture P, Lebon JS, Laliberté É, et al. Low-dose versus high-dose tranexamic acid reduces the risk of nonischemic seizures after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2017;31(5):1611-1617. doi:10.1053/j.jvca.2017.04.026 [PubMed 28803773]Craig T, Aygören-Pürsün E, Bork K, et al. WAO guideline for the management of hereditary angioedema. World Allergy Organ J. 2012;5(12):182-199. doi:10.1097/WOX.0b013e318279affa [PubMed 23282420]CRASH-2 Trial Collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376(9734):23-32. doi:10.1016/S0140-6736(10)60835-5 [PubMed 20554319]CRASH-2 Trial Collaborators. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. 2011;377(9771):1096-1101, 1101.e1-e2. doi:10.1016/S0140-6736(11)60278-X [PubMed 21439633]CRASH-3 Trial Collaborators. Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial [published correction appears in Lancet. 2019;394(10210):1712]. Lancet. 2019;394(10210):1713-1723. doi:10.1016/S0140-6736(19)32233-0 [PubMed 31623894]Cyklokapron (tranexamic acid) [prescribing information]. New York, NY: Pfizer Injectables; March 2021.Cyklokapron (tranexamic acid) [product monograph]. Kirkland, Quebec, Canada: Pfizer Canada Inc; November 2021.Dadure C, Sauter M, Bringuier S, et al. Intraoperative Tranexamic Acid Reduces Blood Transfusion in Children Undergoing Craniosynostosis Surgery: A Randomized Double-Blind Study. Anesthesiology. 2011;114(4):856-861. [PubMed 21358317]Dastrup A, Pottegård A, Hallas J, Overgaard S. Perioperative tranexamic acid treatment and risk of cardiovascular events or death after total hip arthroplasty: a population-based cohort study from National Danish Databases. J Bone Joint Surg Am. 2018;100(20):1742-1749. doi:10.2106/JBJS.17.01518 [PubMed 30334884]Davies D, Howell DA. Tranexamic acid and arterial thrombosis. Lancet. 1977;1(8001):49. doi:10.1016/s0140-6736(77)91690-7 [PubMed 63691]de Guzman R, Polykratis IA, Sondeen JL, Darlington DN, Cap AP, Dubick MA. Stability of tranexamic acid after 12-week storage at temperatures from -20°c to 50°c. Prehosp Emerg Care. 2013;17(3):394-400. doi:10.3109/10903127.2013.792891 [PubMed 23734991]Devereaux PJ, Marcucci M, Painter TW, et al; POISE-3 Investigators. Tranexamic acid in patients undergoing noncardiac surgery. N Engl J Med. 2022;386(21):1986-1997. doi:10.1056/NEJMoa2201171 [PubMed 35363452]Diamond JP, Chandna A, Williams C, Easty DL, Scully C, Eveson J, Richards A. Tranexamic acid-associated ligneous conjunctivitis with gingival and peritoneal lesions. Br J Ophthalmol. 1991;75(12):753-754. doi:10.1136/bjo.75.12.753 [PubMed 1768670]Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2)(suppl):e326S-e350S. doi:10.1378/chest.11-2298 [PubMed 22315266]Dowd NP, Karski JM, Cheng DC, et al. Pharmaco*kinetics of tranexamic acid during cardiopulmonary bypass. Anesthesiology. 2002;97(2):390-399. [PubMed 12151929]Ducloy-Bouthors AS, Jude B, Duhamel A, et al; EXADELI Study Group. High-dose tranexamic acid reduces blood loss in postpartum haemorrhage. Crit Care. 2011;15(2):R117. doi:10.1186/cc10143 [PubMed 21496253]Eaton MP. Antifibrinolytic Therapy in Surgery for Congenital Heart Disease. Anesth Analg. 2008;106(4):1087-1100. [PubMed 18349177]El Hanache H, Verdaguer M, Collin L, et al. Two cases of anaphylaxis to tranexamic acid confirmed by drug provocation test: what about skin tests? J Investig Allergol Clin Immunol. 2021;31(4):351-353. doi:10.18176/jiaci.0651 [PubMed 33136003]Elwatidy S, Jamjoom Z, Elgamal E, et al. Efficacy and Safety of Prophylactic Large Dose of Tranexamic Acid in Spine Surgery: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study. Spine. 2008;33(24):2577-2580. [PubMed 19011538]Erens GA, Walter B, Crowley M. Total hip arthroplasty. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 24, 2022.Farkas H, Martinez-Saguer I, Bork K, et al. International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency. Allergy. 2017;72(2):300‐313. [PubMed 27503784]Farkas H, Varga L, Széplaki G, et al. Management of Hereditary Angioedema in Pediatric Patients. Pediatrics, 2007;120(3):e713-e722. [PubMed 17724112]Faughnan ME, Mager JJ, Hetts SW, et al. Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia. Ann Intern Med. 2020;173(12):989-1001. doi:10.7326/M20-1443 [PubMed 32894695]Fergusson DA, Hébert PC, Mazer CD, et al; BART Investigators. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med. 2008;358(22):2319-2331. doi:10.1056/NEJMoa0802395 [PubMed 18480196]Ferrari FA, Garzon S, Raffaelli R, et al. Tranexamic acid for the prevention and the treatment of primary postpartum haemorrhage: a systematic review. J Obstet Gynaecol. Published online January 7, 2022. doi:10.1080/01443615.2021.2013784 [PubMed 34996342]Ferraris VA, Brown JR Despotis GJ, et al. 2011 Update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists Blood Conservation Clinical Practice Guidelines. Ann Thorac Surg. 2011;91(3):944-982. [PubMed 21353044]Fillingham YA, Ramkumar DB, Jevsevar DS, et al. The safety of tranexamic acid in total joint arthroplasty: a direct meta-analysis. J Arthroplasty. 2018a;33(10):3070-3082.e1. doi:10.1016/j.arth.2018.03.031 [PubMed 29699826]Fillingham YA, Ramkumar DB, Jevsevar DS, et al. Tranexamic acid use in total joint arthroplasty: the clinical practice guidelines endorsed by the American Association of Hip and Knee Surgeons, American Society of Regional Anesthesia and Pain Medicine, American Academy of Orthopaedic Surgeons, Hip Society, and Knee Society. J Arthroplasty. 2018b;33(10):3065-3069. doi:10.1016/j.arth.2018.08.002 [PubMed 30146350]Franchini M, Mengoli C, Marietta M, et al. Safety of intravenous tranexamic acid in patients undergoing majororthopaedic surgery: a meta-analysis of randomised controlled trials. Blood Transfus. 2018;16(1):36-43. doi:10.2450//2017.0219-17 [PubMed 29337665]Frontera JA, Lewin JJ 3rd, Rabinstein AA, et al. Guideline for reversal of antithrombotics in intracranial hemorrhage: a statement for healthcare professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care. 2016;24(1):6-46. doi:10.1007/s12028-015-0222-x [PubMed 26714677]Furtmüller R, Schlag MG, Berger M, et al. Tranexamic acid, a widely used antifibrinolytic agent, causes convulsions by a gamma-aminobutyric acid(A) receptor antagonistic effect. J Pharmacol Exp Ther. 2002;301(1):168-173. doi:10.1124/jpet.301.1.168 [PubMed 11907171]Gaillard S, Dupuis-Girod S, Boutitie F, et al; ATERO Study Group. Tranexamic acid for epistaxis in hereditary hemorrhagic telangiectasia patients: a European cross-over controlled trial in a rare disease. J Thromb Haemost. 2014;12(9):1494-1502. doi:10.1111/jth.12654 [PubMed 25040799]Galvagno S, McCunn M. Anesthesia for adult trauma patients. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 4, 2019.Gaspar R, Brenner B, Ardekian L, Peled M, Laufer D. Use of tranexamic acid mouthwash to prevent postoperative bleeding in oral surgery patients on oral anticoagulant medication. Quintessence Int. 1997;28(6):375-379. [PubMed 9477900]Geisthoff UW, Seyfert UT, Kübler M, Bieg B, Plinkert PK, König J. Treatment of epistaxis in hereditary hemorrhagic telangiectasia with tranexamic acid - a double-blind placebo-controlled cross-over phase IIIB study. Thromb Res. 2014;134(3):565-571. doi:10.1016/j.thromres.2014.06.012 [PubMed 25005464]Gerstein NS, Brierley JK, Culling MD. Left ventricle thrombus after tranexamic acid for spine surgery in an HIV-positive patient. Spine J. 2016;16(2):e77-82. doi:10.1016/j.spinee.2015.10.039 [PubMed 26523960]Gertler R, Gruber M, Grassin-Delyle S, et al. Pharmaco*kinetics of tranexamic acid in neonates and infants undergoing cardiac surgery. Br J Clin Pharmacol. 2017;83(8):1745‐1757. [PubMed 28245519]Gharaibeh A, Savage HI, Scherer RW, Goldberg MF, Lindsley K. Medical interventions for traumatic hyphema. Cochrane Database Syst Rev. 2019;1(1):CD005431. [PubMed 30640411]Gilad O, Merlob P, Stahl B, et al. Outcome following tranexamic acid exposure during breastfeeding. Breastfeed Med. 2014;9(8):407-410. doi: 10.1089/bfm.2014.0027. [PubMed 25025926]Gompels MM, Lock RJ, Abinun M, et al. C1 inhibitor deficiency: consensus document. Clin Exp Immunol. 2005;139(3):379-394. doi:10.1111/j.1365-2249.2005.02726.x [PubMed 15730382]González-Quevedo T, Larco JI, Marcos C, et al. Management of pregnancy and delivery in patients with hereditary angioedema due to C1 inhibitor deficiency. J Investig Allergol Clin Immunol. 2016;26(3):161-167. doi:10.18176/jiaci.0037 [PubMed 27326983]Goobie SM, Faraoni D. Tranexamic acid and perioperative bleeding in children: what do we still need to know? Curr Opin Anaesthesiol. 2019;32(3):343‐352. [PubMed 30893114]Goobie SM, Meier PM, Pereira LM, et al. Efficacy of Tranexamic Acid in Pediatric Craniosynostosis Surgery: A Double-Blind, Placebo-Controlled Trial. Anesthesiology. 2011;114(4):862-871. [PubMed 21364458]Graham EM, Atz AM, Gillis J, et al. Differential effects of aprotinin and tranexamic acid on outcomes and cytokine profiles in neonates undergoing cardiac surgery. J Thorac Cardiovasc Surg. 2012;143(5):1069-1076. [PubMed 22075061]Grant JA, Howard J, Luntley J, et al. Perioperative Blood Transfusion Requirements in Pediatric Scoliosis Surgery: The Efficacy of Tranexamic Acid. J Pediatr Orthop. 2009;29(3):300-304. [PubMed 19305284]Grassin-Delyle S, Couturier R, Abe E, Alvarez JC, Devillier P, Urien S. A practical tranexamic acid dosing scheme based on population pharmaco*kinetics in children undergoing cardiac surgery. Anesthesiology. 2013;118(4):853-862. doi:10.1097/ALN.0b013e318283c83a [PubMed 23343649]Gravlee GP, Spiess B. Pharmacologic prophylaxis for post-Cardiopulmonary bypass bleeding. In: Cardiopulmonary Bypass: Principles and Practice. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008:522-542.Gerstein NS, Brierley JK, Culling MD. Left ventricle thrombus after tranexamic acid for spine surgery in an HIV-positive patient. Spine J. 2016;16(2):e77-82. doi:10.1016/j.spinee.2015.10.039 [PubMed 26523960]Hajmurad OS, Choxi AA, Zahid Z, Dudaryk R. Aortoiliac thrombosis following tranexamic acid administration during urgent cesarean hysterectomy: a case report. A A Case Rep. 2017;9(3):90-93. doi:10.1213/XAA.0000000000000535 [PubMed 28459723]HALT-IT Trial Collaborators. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. Lancet. 2020;395(10241):1927-1936. doi:10.1016/S0140-6736(20)30848-5 [PubMed 32563378]Hillis LD, Smith PK, Anderson JL, et al. 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;124(23):2610-2642. [PubMed 22064600]Hillman J, Fridriksson S, Nilsson O, Yu Z, Saveland H, Jakobsson KE. Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study. J Neurosurg. 2002;97(4):771-778. doi:10.3171/jns.2002.97.4.0771 [PubMed 12405362]Hoots WK, Shapiro AD. Treatment of bleeding and perioperative management in hemophilia A and B. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 23, 2021.Hulde N, Zittermann A, Deutsch MA, von Dossow V, Gummert JF, Koster A. Associations of preoperative stroke and tranexamic acid administration with convulsive seizures in valvular open-heart surgery. J Anesth. 2021;35(3):451-454. doi:10.1007/s00540-021-02924-w [PubMed 33822280]Hulde N, Zittermann A, Deutsch MA, von Dossow V, Gummert JF, Koster A. Tranexamic acid and convulsive seizures after off-pump coronary artery bypass surgery: the role of renal insufficiency. Interact Cardiovasc Thorac Surg. 2019;29(6):852-854. doi:10.1093/icvts/ivz188 [PubMed 31408168]Ijaopo EO, Ijaopo RO, Adjei S. Bilateral pulmonary embolism while receiving tranexamic acid: a case report. J Med Case Rep. 2020;14(1):212. doi:10.1186/s13256-020-02545-z [PubMed 33158458]Imbesi S, Nettis E, Minciullo PL, et al. Hypersensitivity to tranexamic acid: a wide spectrum of adverse reactions. Pharm World Sci. 2010;32(4):416-419. doi:10.1007/s11096-010-9415-8 [PubMed 20632108]Jerath A, Yang QJ, Pang KS, et al. Tranexamic acid dosing for cardiac surgical patients with chronic renal dysfunction: a new dosing regimen. Anesth Analg. 2018;127(6):1323-1332. doi:10.1213/ANE.0000000000002724 [PubMed 29309319]Johnson DJ, Johnson CC, Goobie SM, et al. High-dose versus low-dose tranexamic acid to reduce transfusion requirements in pediatric scoliosis surgery. J Pediatr Orthop. 2017;37(8):e552‐e557. [PubMed 29120963]Johnston LR, Rodriguez CJ, Elster EA, Bradley MJ. Evaluation of military use of tranexamic acid and associated thromboembolic events. JAMA Surg. 2018;153(2):169-175. doi:10.1001/jamasurg.2017.3821 [PubMed 29071337]Kaunitz AM. Abnormal uterine bleeding in nonpregnant reproductive-age patients: management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 29, 2022.Kaku Y, Ito T, Kudo K, Kido-Nakahara M, Nakahara T, Moroi Y, Furue M. Generalized fixed drug eruption induced by tranexamic acid. Eur J Dermatol. 2014;24(3):408-409. doi:10.1684/ejd.2014.2354 [PubMed 24876162]Keijzer R, Wilschut DE, Houmes RJ, et al. Congenital diaphragmatic hernia: to repair on or off extracorporeal membrane oxygenation? J Pediatr Surg. 2012;47(4):631-636. [PubMed 22498373]Kim TK, Chang CB, Kang YG, et al. Clinical value of tranexamic acid in unilateral and simultaneous bilateral TKAs under a contemporary blood-saving protocol: a randomized controlled trial. Knee Surg Sports Traumatol Arthrosc. 2014;22(8):1870-1878. doi:10.1007/s00167-013-2492-1 [PubMed 23592025]Kim YH, Park JW, Kim JS. Chemical thromboprophylaxis is not necessary to reduce risk of thromboembolism with tranexamic acid after total hip arthroplasty. J Arthroplasty. 2017;32(2):641-644. doi:10.1016/j.arth.2016.07.048 [PubMed 27614816]Kiser AS, Cooper GL, Napier JD, Howington GT. Color vision disturbances secondary to oral tranexamic acid. J Am Coll Emerg Physicians Open. 2021;2(3):e12456. doi:10.1002/emp2.12456 [PubMed 34095897]Kitamura H, Matsui I, Itoh N, et al. Tranexamic acid-induced visual impairment in a hemodialysis patient. Clin Exp Nephrol. 2003;7(4):311-4. doi:10.1007/s10157-003-0254-y [PubMed 14712363]Ko BS, Cho KJ, Kim YT, Park JW, Kim NC. Does tranexamic acid increase the incidence of thromboembolism after spinal fusion surgery? Clin Spine Surg. 2020;33(2):E71-E75. doi:10.1097/BSD.0000000000000860 [PubMed 31385850]Ko DH, Kim TH, Kim JW, et al. Tranexamic acid-induced acute renal cortical necrosis in post-endoscopic papillectomy bleeding. Clin Endosc. 2017;50(6):609-613. doi:10.5946/ce.2017.021 [PubMed 28793394]Kratzer S, Irl H, Mattusch C, et al. Tranexamic acid impairs γ-aminobutyric acid receptor type A-mediated synaptic transmission in the murine amygdala: a potential mechanism for drug-induced seizures? Anesthesiology. 2014;120(3):639-69. doi:10.1097/ALN.0000000000000103 [PubMed 24335749]Kurnik NM, Pflibsen LR, Bristol RE, Singh DJ. Tranexamic acid reduces blood loss in craniosynostosis surgery. J Craniofac Surg. 2017;28(5):1325‐1329. [PubMed 28582303]Lam MS. Extemporaneous compounding of oral liquid dosage formulations and alternative drug delivery methods for anticancer drugs. Pharmacotherapy. 2011;31(2):164-192. doi:10.1592/phco.31.2.164 [PubMed 21275495]Lecker I, Wang DS, Romaschin AD, Peterson M, Mazer CD, Orser BA. Tranexamic acid concentrations associated with human seizures inhibit glycine receptors. J Clin Invest. 2012;122(12):4654-4666. doi:10.1172/JCI63375 [PubMed 23187124]Lecker I, Wang DS, Whissell PD, Avramescu S, Mazer CD, Orser BA. Tranexamic acid-associated seizures: causes and treatment. Ann Neurol. 2016;79(1):18-26. doi:10.1002/ana.24558 [PubMed 26580862]Leverett GD, Marriott A. Intravenous tranexamic acid and thromboembolic events in hip fracture surgery: a systematic review and meta-analysis. Orthop Traumatol Surg Res. 2022 May 25:103337. doi:10.1016/j.otsr.2022.103337 [PubMed 35643364]Levin E, Wu J, Devine DV, et al. Hemostatic Parameters and Platelet Activation Marker Expression in Cyanotic and Acyanotic Pediatric Patients Undergoing Cardiac Surgery in the Presence of Tranexamic Acid. Thromb Haemost. 2000;83(1):54-59. [PubMed 10669155]Levy JH, Freiberger DJ, Roback J. Hereditary angioedema: current and emerging treatment options. Anesth Analg. 2010;110(5):1271-1280. doi:10.1213/ANE.0b013e3181d7ac98 [PubMed 20418292]Levy JH, Koster A, Quinones QJ, Milling TJ, Key NS. Antifibrinolytic therapy and perioperative considerations. Anesthesiology. 2018;128(3):657-670. doi:10.1097/ALN.0000000000001997 [PubMed 29200009]Lin Z, Xiaoyi Z. Tranexamic acid-associated seizures: a meta-analysis. Seizure. 2016;36:70-73. doi:10.1016/j.seizure.2016.02.011 [PubMed 26967164]Li PH, Trigg C, Rutkowski R, Rutkowski K. Anaphylaxis to tranexamic acid-a rare reaction to a common drug. J Allergy Clin Immunol Pract. 2017;5(3):839-841. doi:10.1016/j.jaip.2016.12.014 [PubMed 28117269]Li S, Ahmadzia HK, Guo D, et al. Population pharmaco*kinetics and pharmacodynamics of tranexamic acid in women undergoing caesarean delivery. Br J Clin Pharmacol. 2021;87(9):3531-3541. doi:10.1111/bcp.14767 [PubMed 33576009]Lu VM, Ho YT, Nambiar M, Mobbs RJ, Phan K. The perioperative efficacy and safety of antifibrinolytics in adult spinal fusion surgery: a systematic review and meta-analysis. Spine (Phila Pa 1976). 2018;43(16):E949-E958. doi:10.1097/BRS.0000000000002580 [PubMed 30063223]Lysteda (tranexamic acid) (prescribing information). Parsippany, NJ: Ferring Pharmaceuticals Inc; December 2020.MacGillivray RG, Tarabichi SB, Hawari MF, Raoof NT. Tranexamic acid to reduce blood loss after bilateral total knee arthroplasty: a prospective, randomized double blind study. J Arthroplasty. 2011;26(1):24-28. doi:10.1016/j.arth.2009.11.013 [PubMed 20171048]Machado AM, Pires RM, Martins RO, et al. Pregnancy and postpartum in hereditary angioedema with C1 inhibitor deficit in women who have no access to therapy. J Investig Allergol Clin Immunol. 2017;27(5):322-323. doi:10.18176/jiaci.0175 [PubMed 29057741]Madsen RV, Nielsen CS, Kallemose T, Husted H, Troelsen A. Low risk of thromboembolic events after routine administration of tranexamic acid in hip and knee arthroplasty. J Arthroplasty. 2017;32(4):1298-1303. doi:10.1016/j.arth.2016.10.015 [PubMed 27843042]Maniar RN, Kumar G, Singhi T, Nayak RM, Maniar PR. Most effective regimen of tranexamic acid in knee arthroplasty: a prospective randomized controlled study in 240 patients. Clin Orthop Relat Res. 2012;470(9):2605-2612. doi:10.1007/s11999-012-2310-y [PubMed 22419350]Manji RA, Grocott HP, Leake J, et al. Seizures following cardiac surgery: the impact of tranexamic acid and other risk factors. Can J Anaesth. 2012;59(1):6-13. doi:10.1007/s12630-011-9618-z [PubMed 22065333]Martin DT, Gries H, Esmonde N, et al. Implementation of a tranexamic acid protocol to reduce blood loss during cranial vault remodeling for craniosynostosis. J Craniofac Surg. 2016;27(6):1527‐1531. [PubMed 27557459]Martin GM, Roe J. Total knee arthroplasty. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 7, 2020.Maurer M, Magerl M, Ansotegui I, et al. The international WAO/EAACI guideline for the management of hereditary angioedema-the 2017 revision and update. Allergy. 2018;73(8):1575-1596. doi:10.1111/all.13384 [PubMed 29318628]Maurer M, Magerl M, Betschel S, et al. The international WAO/EAACI guideline for the management of hereditary angioedema-the 2021 revision and update. Allergy. Published online January 10, 2022. doi:10.1111/all.15214 [PubMed 35006617]McCluskey SV, Sztajnkrycer MD, Jenkins DA, Zietlow SP, Berns KS, Park MS. Stability of tranexamic acid in 0.9% sodium chloride, stored in type 1 glass vials and ethylene/propylene copolymer plastic containers. Int J Pharm Compd. 2014;18(5):432-437. [PubMed 25577894]Meaidi A, Mørch L, Torp-Pedersen C, Lidegaard O. Oral tranexamic acid and thrombosis risk in women. EClinicalMedicine. 2021;35:100882. doi:10.1016/j.eclinm.2021.100882 [PubMed 34124632]Milingos DS, Madhuvrata P, Dean J, et al. Hereditary angioedema and pregnancy: successful management of recurrent and frequent attacks of angioedema with C1-inhibitor concentrate, danazol and tranexamic acid - a case report. Obstet Med. 2009;2(3):123-125. doi:10.1258/om.2009.090003 [PubMed 27582827]Mindel JS. Problems in the use of tranexamic acid by ophthalmologists. Arch Ophthalmol. 1989;107(4):486-487. doi:10.1001/archopht.1989.01070010500006 [PubMed 2705908]Montes FR, Pardo DF, Carreño M, Arciniegas C, Dennis RJ, Umaña JP. Risk factors associated with postoperative seizures in patients undergoing cardiac surgery who received tranexamic acid: a case-control study. Ann Card Anaesth. 2012;15(1):6-12. doi:10.4103/0971-9784.91467 [PubMed 22234015]Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg. 2012;147(2):113-119. [PubMed 22006852]Muhunthan K, Balakumar S, Navaratnaraja TS, Premakrishna S, Arulkumaran S. Plasma concentrations of tranexamic acid in postpartum women after oral administration. Obstet Gynecol. 2020;135(4):945-948. doi:10.1097/AOG.0000000000003750 [PubMed 32168220]Muñoz M, Stensballe J, Ducloy-Bouthors AS, et al. Patient blood management in obstetrics: prevention and treatment of postpartum haemorrhage. A NATA consensus statement. Blood Transfus. 2019;17(2):112-136. doi:10.2450/2019.0245-18 [PubMed 30865585]Murao S, Nakata H, Roberts I, Yamakawa K. Effect of tranexamic acid on thrombotic events and seizures in bleeding patients: a systematic review and meta-analysis. Crit Care. 2021;25(1):380. doi:10.1186/s13054-021-03799-9 [PubMed 34724964]Murdaca G, Greco M, Vassallo C, Gangemi S. Tranexamic acid adverse reactions: a brief summary for internists and emergency doctors. Clin Mol Allergy. 2020;18:16. doi:10.1186/s12948-020-00131-8 [PubMed 32908455]Murkin JM, Falter F, Granton J, et al. High-Dose Tranexamic Acid is Associated With Nonischemic Clinical Seizures in Cardiac Surgical Patients. Anesth Anal. 2010;110(2):350-353. [PubMed 19996135]Myers SP, Kutcher ME, Rosengart MR, et al. Tranexamic acid administration is associated with an increased risk of posttraumatic venous thromboembolism. J Trauma Acute Care Surg. 2019;86(1):20-27. doi:10.1097/TA.0000000000002061 [PubMed 30239375]Myles PS, Smith JA, Forbes A, et al; ATACAS Investigators of the ANZCA Clinical Trials Network. Tranexamic acid in patients undergoing coronary-artery surgery. N Engl J Med. 2017;376(2):136-148. doi:10.1056/NEJMoa1606424 [PubMed 27774838]National Alert Network (NAN). NAN Alert. Dangerous wrong-route errors with tranexamic acid. https://www.ismp.org/sites/default/files/attachments/2020-09/NAN%20Alert%2020200909.pdf. Published September 9, 2020. Accessed September 14, 2020.National Institute for Health and Care Excellence. Drug allergy: diagnosis and management. Published September 3, 2014. Accessed October 23, 2020. https://www.nice.org.uk/guidance/cg183Neilipovitz DT, Murto K, Hall L, et al. A Randomized Trial of Tranexamic Acid to Reduce Blood Transfusion for Scoliosis Surgery. Anesth Analg. 2001;93(1):82-87. [PubMed 11429344]Nishida T, Kinosh*ta T, Yamakawa K. Tranexamic acid and trauma-induced coagulopathy. J Intensive Care. 2017;5:5. doi:10.1186/s40560-016-0201-0 [PubMed 28729903]Novikova N, Hofmeyr GJ, Cluver C. Tranexamic acid for preventing postpartum haemorrhage. Cochrane Database Syst Rev. 2015;(6):CD007872. doi:10.1002/14651858.CD007872.pub3 [PubMed 26079202]Nuttall GA, Gutierrez MC, Dewey JD, et al. A preliminary study of a new tranexamic acid dosing schedule for cardiac surgery. J Cardiothorac Vasc Anesth. 2008;22(2):230-235. doi:10.1053/j.jvca.2007.12.016 [PubMed 18375325]O'Neil ER, Schmees LR, Resendiz K, Justino H, Anders MM. Inhaled tranexamic acid as a novel treatment for pulmonary hemorrhage in critically ill pediatric patients: an observational study. Crit Care Explor. 2020;2(1):e0075. [PubMed 32166295]Pabinger I, Fries D, Schöchl H, Streif W, Toller W. Tranexamic acid for treatment and prophylaxis of bleeding and hyperfibrinolysis. Wien Klin Wochenschr. 2017;129(9-10):303-316. doi:10.1007/s00508-017-1194-y [PubMed 28432428]Parsons MR, Merritt DR, Ramsay RC. Retinal artery occlusion associated with tranexamic acid therapy. Am J Ophthalmol. 1988;105(6):688-689. doi:10.1016/0002-9394(88)90069-4 [PubMed 3163896]Patatanian E, Fugate SE. Hemostatic mouthwashes in anticoagulated patients undergoing dental extraction. Ann Pharmacother. 2006;40(12):2205-2210. doi:10.1345/aph.1H295 [PubMed 17090725]Patel S, Robertson B, McConachie I. Catastrophic drug errors involving tranexamic acid administered during spinal anaesthesia. Anaesthesia. 2019;74(7):904-914. doi:10.1111/anae.14662 [PubMed 30985928]Pavord S, Myers B. Bleeding and thrombotic complications of kidney disease. Blood Rev. 2011;25(6):271-278. doi:10.1016/j.blre.2011.07.001 [PubMed 21872374]Pavord S, Rayment R, Madan B, et al; Royal College of Obstetricians and Gynaecologists. Management of inherited bleeding disorders in pregnancy. Green-top Guideline No. 71. BJOG. 2017;124(8):e193-e263. doi:10.1111/1471-0528.14592 [PubMed 28447403]Pennington Z, Ehresman J, Schilling A, et al. Influence of tranexamic acid use on venous thromboembolism risk in patients undergoing surgery for spine tumors. J Neurosurg Spine. 2021:1-11. doi:10.3171/2021.1.SPINE201935 [PubMed 34388705]Porter SB, Spaulding AC, Duncan CM, Wilke BK, Pagnano MW, Abdel MP. Tranexamic acid was not associated with increased complications in high-risk patients with intertrochanteric fracture. J Bone Joint Surg Am. 2022;104(13):1138-1147. doi:10.2106/JBJS.21.01389 [PubMed 35775092]Post R, Germans MR, Tjerkstra MA, et al; ULTRA Investigators. Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial. Lancet. 2021;397(10269):112-118. doi:10.1016/S0140-6736(20)32518-6 [PubMed 33357465]Powers WJ, Rabinstein AA, Ackerson T, et al; American Heart Association Stroke Council. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46-e110. doi:10.1161/STR.0000000000000158 [PubMed 29367334]Pretel Irazabal M, Marques Martin L, Aguado Gil L, Idoate Gastearena MA. Tranexamic acid-induced toxic epidermal necrolysis. Ann Pharmacother. 2013;47(3):e16. doi:10.1345/aph.1R637 [PubMed 23447480]Rahmani B, Jahadi HR. Comparison of Tranexamic Acid and Prednisolone in the Treatment of Traumatic Hyphema. Ophthalmology. 1999;106(2):375-379. [PubMed 9951493]Rajajee V. Management of acute moderate and severe traumatic brain injury. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 12, 2020.Refer to manufacturer labeling.Reid RW, Zimmerman AA, Laussen PC, et al. The Efficacy of Tranexamic Acid Versus Placebo in Decreasing Blood Loss in Pediatric Patients Undergoing Repeat Cardiac Surgery. Anesth Analg. 1997;84(5):990-996. [PubMed 9141920]Roos Y. Antifibrinolytic treatment in subarachnoid hemorrhage: a randomized placebo-controlled trial. STAR Study Group. Neurology. 2000;54(1):77-82. [PubMed 10636129]Roos YB, Rinkel GJ, Vermeulen M, Algra A, van Gijn J. Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2003;(2):CD001245. doi:10.1002/14651858.CD001245 [PubMed 12804399]Royal College of Paediatrics and Child Health. Evidence statement: Major trauma and the use of tranexamic acid in children. November 2012. https://www.rcem.ac.uk/docs/External%20Guidance/10k.%20Major%20trauma%20and%20the%20use%20of%20tranexamic%20acid%20in%20children%20Evidence%20statement%20(RCPCH,%20Nov%202012).pdf.Saccone G, Della Corte L, D'Alessandro P, et al. Prophylactic use of tranexamic acid after vagin*l delivery reduces the risk of primary postpartum hemorrhage. J Matern Fetal Neonatal Med. 2019:1-9. doi:10.1080/14767058.2019.1571576 [PubMed 30704334]Schindler E, Photiadis J, Sinzobahamvya N, Döres A, Asfour B, Hraska V. Tranexamic acid: an alternative to aprotinin as antifibrinolytic therapy in pediatric congenital heart surgery. Eur J Cardiothorac Surg. 2011;39(4):495-499. [PubMed 20832330]Schrijvers R, Gilissen L, Chiriac AM, Demoly P. Pathogenesis and diagnosis of delayed-type drug hypersensitivity reactions, from bedside to bench and back. Clin Transl Allergy. 2015;5:31. doi: 10.1186/s13601-015-0073-8 [PubMed 26339470]Segrelles Calvo G, De Granda-Orive I, López Padilla D. Inhaled tranexamic acid as an alternative for hemoptysis treatment. Chest. 2016;149(2):604. doi:10.1016/j.chest.2015.10.016 [PubMed 26867844]Sentilhes L, Sénat MV, Le Lous M, et al; Groupe de Recherche en Obstétrique et Gynécologie. Tranexamic acid for the prevention of blood loss after cesarean delivery. N Engl J Med. 2021;384(17):1623-1634. doi:10.1056/NEJMoa2028788 [PubMed 33913639]Sentilhes L, Winer N, Azria E, et al; Groupe de Recherche en Obstétrique et Gynécologie. Tranexamic acid for the prevention of blood loss after vagin*l delivery. N Engl J Med. 2018;379(8):731-742. doi:10.1056/NEJMoa1800942. [PubMed 30134136]Sethna NF, Zurakowski D, Brustowicz RM, et al. Tranexamic Acid Reduces Intraoperative Blood Loss in Pediatric Patients Undergoing Scoliosis Surgery. Anesthesiology. 2005;102(4):727-732. [PubMed 15791100]Shakur H, Elbourne D, Gülmezoglu M, et al. The WOMAN Trial (World Maternal Antifibrinolytic Trial): tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind placebo controlled trial. Trials. 2010;11:40. doi:10.1186/1745-6215-11-40 [PubMed 20398351]Shapiro F, Zurakowski D, Sethna NF. Tranexamic Acid Diminishes Intraoperative Blood Loss and Transfusion in Spinal Fusions for duch*enne Muscular Dystrophy Scoliosis. Spine (Phila Pa 1976). 2007;32(20):2278-2283. [PubMed 17873823]Sharma V, Katznelson R, Jerath A, et al. The association between tranexamic acid and convulsive seizures after cardiac surgery: a multivariate analysis in 11 529 patients. Anaesthesia. 2014;69(2):124-130. doi:10.1111/anae.12516 [PubMed 24588023]Shi J, Zhou C, Pan W, et al. Effect of high- vs low-dose tranexamic acid infusion on need for red blood cell transfusion and adverse events in patients undergoing cardiac surgery: the OPTIMAL Randomized Clinical Trial. JAMA. 2022;328(4):336-347. doi:10.1001/jama.2022.10725 [PubMed 35881121]Shimizu K, Toda Y, Iwasaki T, et al. Effect of tranexamic acid on blood loss in pediatric cardiac surgery: a randomized trial. J Anesth. 2011;25(6):823‐830. [PubMed 21947753]Sigaut S, Tremey B, Ouattara A, et al. Comparison of two doses of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass. Anesthesiology. 2014;120(3):590-600. doi:10.1097/ALN.0b013e3182a443e8 [PubMed 23903022]Sindet-Pedersen S. Distribution of tranexamic acid to plasma and saliva after oral administration and mouth rinsing: a pharmaco*kinetic study. J Clin Pharmacol. 1987;27(12):1005-1008. doi:10.1002/j.1552-4604.1987.tb05605.x [PubMed 3437064]Simonazzi G, Bisulli M, Saccone G, Moro E, Marshall A, Berghella V. Tranexamic acid for preventing postpartum blood loss after cesarean delivery: a systematic review and meta-analysis of randomized controlled trials. Acta Obstet Gynecol Scand. 2016;95(1):28-37. doi:10.1111/aogs.12798 [PubMed 26698831]Smetzer J, Cohen M, Shastay A, Jenkins R, Litman RS, eds. Dangerous wrong-route errors with tranexamic acid-a major cause for concern. ISMP Medication Safety Alert! Acute Care Edition. 2019;24(10):2-4.Song Y, Izumi N, Potts LB, Yoshida A. Tranexamic acid-induced ligneous conjunctivitis with renal failure showed reversible hypoplasminogenaemia. BMJ Case Rep. 2014;2014:bcr2014204138. doi:10.1136/bcr-2014-204138 [PubMed 24842363]Spinella PC, Bochicchio K, Thomas KA, et al. The risk of thromboembolic events with early intravenous 2- and 4-g bolus dosing of tranexamic acid compared to placebo in patients with severe traumatic bleeding: a secondary analysis of a randomized, double-blind, placebo-controlled, single-center trial. Transfusion. 2022;62 (Suppl 1):S139-S150. doi:10.1111/trf.16962 [PubMed 35765921]Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al; Treatment Guidelines Working Group on behalf of The World Federation of Hemophilia. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1-e47. doi:10.1111/j.1365-2516.2012.02909.x [PubMed 22776238]Starke RM, Connolly ES Jr; Participants in the International Multi-Disciplinary Consensus Conference on the Critical Care Management of Subarachnoid Hemorrhage. Rebleeding after aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2011;15(2):241-246. doi:10.1007/s12028-011-9581-0 [PubMed 21761274]Taeuber I, Weibel S, Herrmann E, et al. Association of intravenous tranexamic acid with thromboembolic events and mortality: a systematic review, meta-analysis, and meta-regression. JAMA Surg. 2021;156(6):e210884. doi:10.1001/jamasurg.2021.0884 [PubMed 33851983]Tranexamic acid in sodium chloride injection [prescribing information]. Lenoir, NC: Exela Pharma Sciences LLC; July 2020.van der Staak FH, de Haan AF, Geven WB, et al. Surgical Repair of Congenital Diaphragmatic Hernia During Extracorporeal Membrane Oxygenation: Hemorrhagic Complications and the Effect of Tranexamic Acid. J Ped Surg. 1997;32(4):594-599. [PubMed 9126762]van Galen KP, Engelen ET, Mauser-Bunschoten EP, van Es RJ, Schutgens RE. Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or von Willebrand disease undergoing minor oral surgery or dental extractions. Cochrane Database Syst Rev. 2019;4:CD011385. doi:10.1002/14651858.CD011385.pub3 [PubMed 31002742]Vangsted P, Nielsen PJ. Tranexamic Acid and Traumatic Hyphaema, A Prospective Study. Acta Ophthalmol (Copenh). 1983;61(3):447-453. [PubMed 6353843]Verma K, Errico TJ, Vaz KM, et al. A prospective, Randomized, Double-Blinded Single-Site Control Study Comparing Blood Loss Prevention of Tranexamic Acid (TXA) to Epsilon Aminocaproic Acid (EACA) for Corrective Spinal Surgery. BMC Surg. 2010;10:13. [PubMed 20370916]Verstraete M. Clinical application of inhibitors of fibrinolysis. Drugs. 1985;29(3):236-261. [PubMed 2580684]Wand O, Guber E, Guber A, Epstein Shochet G, Israeli-Shani L, sh*trit D. Inhaled tranexamic acid for hemoptysis treatment: a randomized controlled trial. Chest. 2018;154(6):1379-1384. doi:10.1016/j.chest.2018.09.026 [PubMed 30321510]Wijetilleka S, Yeo DCM, Sharma B. Central retinal artery occlusion in a 30-year-old woman taking tranexamic acid. BMJ Case Rep. 2017;2017:bcr2016218246. doi:10.1136/bcr-2016-218246 [PubMed 28705840]WOMAN Trial Collaborators. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial [published correction appears in Lancet. 2017;389(10084):2104]. Lancet. 2017;389(10084):2105-2116. doi:10.1016/S0140-6736(17)30638-4 [PubMed 28456509]Wong J, El Beheiry H, Rampersaud YR, et al. Tranexamic acid reduces perioperative blood loss in adult patients having spinal fusion surgery. Anesth Analg. 2008;107(5):1479-1486. doi:10.1213/ane.0b013e3181831e44 [PubMed 18931202]World Health Organization. WHO Recommendation on Tranexamic Acid for the Treatment of Postpartum Haemorrhage. Geneva: World Health Organization; 2017. http://www.who.int/reproductivehealth/publications/tranexamic-acid-pph-treatment/en/. Published 2017. Accessed April 6, 2018.Xia Y, Griffiths BB, Xue Q. Tranexamic acid for postpartum hemorrhage prevention in vagin*l delivery: a meta-analysis. Medicine (Baltimore). 2020;99(3):e18792. doi:10.1097/MD.0000000000018792 [PubMed 32011478]Xiao C, Zhang S, Long N, Yu W, Jiang Y. Is intravenous tranexamic acid effective and safe during hip fracture surgery? An updated meta-analysis of randomized controlled trials. Arch Orthop Trauma Surg. 2019;139(7):893-902. doi:10.1007/s00402-019-03118-6 [PubMed 30637503]Xie Q, Huang CJ, Gu KP, Yao YX. Circulation collapse caused by intracardiac thrombosis associated with tranexamic acid administration: a case report. Medicine (Baltimore). 2021;100(47):e27997. doi:10.1097/MD.0000000000027997 [PubMed 34964796]Yang QJ, Jerath A, Bies RR, Wąsowicz M, Pang KS. Pharmaco*kinetic modeling of tranexamic acid for patients undergoing cardiac surgery with normal renal function and model simulations for patients with renal impairment. Biopharm Drug Dispos. 2015;36(5):294-307. doi:10.1002/bdd.1941 [PubMed 25704361]Yee BE, Wissler RN, Zanghi CN, Feng C, Eaton MP. The effective concentration of tranexamic acid for inhibition of fibrinolysis in neonatal plasma in vitro. Anesth Analg. 2013;117(4):767-772. doi:10.1213/ANE.0b013e3182a22258 [PubMed 24023015]Zaffar N, Ravichakaravarthy T, Faughnan ME, Shehata N. The use of anti-fibrinolytic agents in patients with HHT: a retrospective survey. Ann Hematol. 2015;94(1):145-152. doi:10.1007/s00277-014-2169-y [PubMed 25064693]Zufferey PJ, Miquet M, Quenet S, et al; Tranexamic Acid in Hip-Fracture Surgery (THIF) Study Investigators. Tranexamic acid in hip fracture surgery: a randomized controlled trial. Br J Anaesth. 2010;104(1):23-30. doi:10.1093/bja/aep314 [PubMed 19926634]Zuraw B, Farkas H. Hereditary angioedema (due to C1 inhibitor deficiency): general care and long-term prophylaxis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 11, 2022.Zuraw BL, Bernstein JA, Lang DM, et al. A focused parameter update: hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema. J Allergy Clin Immunol. 2013;131(6):1491‐1493. [PubMed 23726531]Topic 10011 Version 410.0