Version May 2024
Itraconazole can cause or exacerbate congestive heart failure (CHF). When itraconazole was administered intravenously (IV) to dogs and healthy human volunteers, negative inotropic effects were seen. Do not administer itraconazole for the treatment of onychomycosis in patients with evidence of ventricular dysfunction, such as CHF or a history of CHF. If signs or symptoms of CHF occur during administration of itraconazole oral solution or capsule (65 mg [Tolsura]), reassess continued itraconazole use. If signs or symptoms of CHF occur during administration of itraconazole capsules (100 mg [Sporanox]), discontinue administration.
Coadministration of the following drugs is contraindicated with itraconazole: methadone, disopyramide, dofetilide, dronedarone, quinidine, isavuconazole, ergot alkaloids (eg, dihydroergotamine, ergometrine [ergonovine], ergotamine, methylergometrine [methylergonovine]), irinotecan, lurasidone, oral midazolam, pimozide, triazolam, felodipine, nisoldipine, ivabradine, ranolazine, eplerenone, cisapride, naloxegol, lomitapide, lovastatin, simvastatin, avanafil, ticagrelor, finerenone, and voclosporin. In addition, coadministration with colchicine, fesoterodine, and solifenacin is contraindicated in subjects with varying degrees of renal or hepatic impairment, and coadministration with eliglustat is contraindicated in subjects who are poor or intermediate metabolizers of CYP2D6 and in subjects taking strong or moderate CYP2D6 inhibitors. Coadministration with venetoclax is contraindicated in subjects with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) during the dose initiation and ramp-up phase of venetoclax. Coadministration with itraconazole can cause elevated plasma concentrations of these drugs and may increase or prolong both the pharmacologic effects and/or adverse reactions to these drugs. For example, increased plasma concentrations of some of these drugs can lead to QT prolongation and ventricular tachyarrhythmias including occurrences of torsades de pointes, a potentially fatal arrhythmia.
Dosage guidance:
Dosing: For most indications, adjust dose based on trough serum concentration to ensure efficacy and avoid toxicity. Timing and frequency of concentration monitoring is individualized (Ref).
Dosage form information: Due to differences in bioavailability, itraconazole formulations are not interchangeable. Generally, the oral solution is preferred because of improved absorption (Ref) Tolsura (65 mg capsule) is dosed differently than other formulations.
Aspergillosis:
Allergic bronchopulmonary: Oral: Solution or capsule (100 mg): 200 mg twice daily for ≥16 weeks in combination with systemic corticosteroids (Ref); may give a loading dose of 200 mg 3 times daily for the first 3 days of therapy. Note: Some experts reserve for patients who are unable to taper corticosteroids or have an exacerbation of allergic bronchopulmonary aspergillosis (Ref).
Chronic cavitary pulmonary: Oral: Solution or capsule (100 mg): 200 mg twice daily for ≥6 months (Ref); some patients require prolonged, potentially lifelong therapy (Ref).
Invasive (alternative agent): Note: Itraconazole is generally not recommended; reserve for patients with mild disease when other therapies are unavailable or cannot be used (Ref). Oral:
Solution (preferred) or capsule (100 mg): 200 mg twice daily (Ref); may give a loading dose of 200 mg 3 times daily for the first 3 days of therapy (Ref).
Capsule (65 mg): 130 mg once or twice daily; may give a loading dose of 130 mg 3 times daily for the first 3 days of therapy.
Duration: Minimum of 6 to 12 weeks, depending on degree/duration of immunosuppression, disease site, and response to therapy (Ref); immunosuppressed patients may require more prolonged treatment (Ref).
Blastomycosis:
Note: For initial treatment of mild to moderate disease or step-down therapy after amphotericin B for more severe infection (Ref): Oral:
Solution or capsule (100 mg):
Loading dose: 200 mg 3 times daily for 3 days (Ref).
Maintenance dose:
Mild to moderate disease in immunocompetent patients: 200 mg once to twice daily (Ref).
Moderately severe to severe disease and immunocompromised patients: 200 mg twice daily (Ref).
CNS infection (alternative agent): 200 mg 2 to 3 times daily (Ref).
Capsule (65 mg): 130 mg once daily; if no improvement or if there is evidence of progressive fungal infection, increase dose in 65 mg increments to a maximum of 260 mg/day (doses >130 mg/day should be given in 2 divided doses). May give a loading dose of 130 mg 3 times daily for the first 3 days of therapy.
Duration: 6 to 12 months; ≥12 months is recommended for patients with moderately severe to severe disseminated infection, osteoarticular or CNS infection, and for all immunocompromised patients (Ref).
Candidiasis:
Note: Generally reserved for fluconazole-refractory disease or as an alternative initial agent. Capsule formulation is not recommended (Ref).
Esophageal: Oral: Solution: 200 mg once daily for 14 to 28 days (Ref).
Oropharyngeal: Oral: Solution: 200 mg once daily (Ref). Duration is 7 to 14 days for initial therapy (Ref) or up to 28 days for refractory disease (Ref).
Vulvovaginal (uncomplicated) in patients with HIV (alternative agent) (off-label use): Oral: Solution: 200 mg once daily for 3 to 7 days (Ref).
Coccidioidomycosis (off-label use):
Note: Initial parenteral antifungal therapy is warranted for severe disease (Ref).
Bone and/or joint infection: Oral: Solution or capsule (100 mg): 200 mg twice daily for ≥3 years; in some cases, lifelong treatment is needed (Ref).
Meningitis (alternative agent): Oral: Solution or capsule (100 mg): 200 mg 2 to 4 times daily. Duration is lifelong because of the high relapse rate (Ref).
Pneumonia, primary infection: Note: Reserve treatment for patients with or at risk for severe disease (eg, extensive pulmonary involvement, patients who are immunocompromised) (Ref).
Oral: Solution or capsule (100 mg): 200 mg twice daily; for severe disease, use in combination with initial therapy with amphotericin B. Duration is typically 3 to 6 months, but can vary depending on comorbid conditions, severity of disease, and response to therapy (Ref).
Pneumonia, symptomatic chronic cavitary and/or cavitary disease in patients who are immunocompromised: Oral: Solution or capsule (100 mg): 200 mg twice daily for ≥12 months. In patients with ruptured cavities, the duration may be shorter, but depends on postoperative course (Ref).
Soft tissue infection (not associated with bone infection): Oral: Solution or capsule (100 mg): 200 mg twice daily for at least 6 to 12 months (Ref).
Histoplasmosis:
Treatment, initial therapy for mild to moderate disease or step-down therapy after amphotericin B for more severe infection: Oral:
Solution or capsule (100 mg):
Loading dose: 200 mg 3 times daily for 3 days (Ref).
Maintenance dose:
Mild to moderate disease in immunocompetent patients: 200 mg once to twice daily (Ref); some experts favor 200 mg twice daily (Ref).
Moderately severe to severe or disseminated disease and immunocompromised patients: 200 mg twice daily (Ref).
CNS infection: 200 mg 2 to 3 times daily (Ref); some experts favor 200 mg 3 times daily for patients with HIV and CNS infection (Ref).
Capsule (65 mg): 130 mg once daily; if no improvement or if there is evidence of progressive fungal infection, increase dose in 65 mg increments to a maximum of 260 mg/day (doses >130 mg/day should be given in 2 divided doses). May give a loading dose of 130 mg 3 times daily for the first 3 days of therapy.
Duration: 6 to 12 weeks for mild to moderate pulmonary infection and ≥12 weeks for moderately severe to severe pulmonary infection (Ref); ≥12 months for immunocompromised patients and/or patients with CNS, chronic cavitary pulmonary, or disseminated infection (Ref).
Long-term suppression therapy (secondary prophylaxis) in select immunocompromised patients: Solution or capsule (100 mg): 200 mg once to twice daily (Ref).
Prophylaxis, primary prophylaxis in patients with HIV (off-label use): Note: Not routinely given (Ref); some experts recommend primary prophylaxis in patients with CD4 count <150 cells/mm3 and increased risk due to occupational exposure or residence in a hyperendemic area (Ref).
Oral: Solution or capsule (100 mg): 200 mg once daily (Ref).
Onychomycosis (alternative agent):
Note: For dermatophyte onychomycosis, reserve for patients unable to take preferred agents (Ref).
Oral: Capsule (100 mg):
Continuous dosing: 200 mg once daily for 6 weeks (fingernail [off-label use]) (Ref) or 12 weeks (toenail) (Ref).
Pulsed dosing: 200 mg twice daily for 1 week; repeat every 4 weeks for 2 months (fingernail) or 3 months (toenail). Note: For toenail onychomycosis, some data suggest higher cure rates after 6 months compared to 3 months (Ref).
Paracoccidioidomycosis (off-label use): Note: For initial treatment of mild to moderate infection or step-down therapy following initial intravenous therapy for severe infection.
Oral: Solution or capsule (100 mg): 100 to 200 mg once daily. Duration is generally 6 to 12 months but may be >2 years for severe disease (Ref).
Prophylaxis against invasive fungal infections (off-label use):
Chronic granulomatous disease: Oral: Solution or capsule (100 mg): 200 mg once daily; duration is lifelong (Ref).
Hematologic malignancy or hematopoietic cell transplant (alternative agent for prophylaxis against Candida spp.): Oral: Solution: 200 mg twice daily. Duration varies based on degree and duration of immunosuppression (Ref).
Solid organ transplant, select patients (eg, lung transplant recipients) (alternative agent): Oral: Solution: 200 mg twice daily; duration varies by patient risk factors and among transplant centers (Ref).
Sporotrichosis (off-label use):
Cutaneous or lymphocutaneous infection: Oral: Solution or capsule (100 mg):
Initial therapy: 100 to 200 mg once daily (Ref); some experts favor 200 mg once daily (Ref).
Refractory to daily itraconazole: 200 mg twice daily (Ref).
Duration: 2 to 4 weeks after lesion resolution, usually for a total of 3 to 6 months (Ref).
Extracutaneous infection: Note: Initial therapy with amphotericin B is recommended for patients with disseminated, meningeal, or severe pulmonary infection.
Oral: Solution or capsule (100 mg): 200 mg twice daily for ≥1 year (Ref).
Talaromycosis (formerly penicilliosis) (off-label use):
Treatment: Oral: Solution or capsule (100 mg):
Mild disease (skin lesions without bloodstream infection): 200 mg 3 times daily for 3 days, then 200 mg twice daily for 8 to 12 weeks, then continue with long-term suppression therapy (Ref).
Moderate to severe disease, oral step-down therapy after initial amphotericin B: 200 mg 3 times daily for 3 days, then 200 mg twice daily for 10 weeks, then continue with long-term suppression therapy (Ref).
Long-term suppression therapy (secondary prophylaxis): 200 mg once daily until cellular immunity is restored (for patients with HIV, can be discontinued once CD4 count >100 cells/mm3 and virologic suppression with antiretroviral therapy has been sustained for ≥6 months) (Ref).
Prophylaxis, primary, for patients with HIV and CD4 cell count <100 cells/mm3 who are not starting antiretroviral therapy and reside in or travel to highly endemic areas in northern Thailand, Vietnam, and Southern China:
Oral: Solution or capsule (100 mg): 200 mg once daily; for residents of highly endemic areas, continue until CD4 count >100 cells/mm3 and virologic suppression with antiretroviral therapy has been sustained for ≥6 months; for travelers, begin prophylaxis 3 days prior to travel and continue for 1 week after travel (Ref).
Tinea infections (alternative agent) (off-label use):
Fungal folliculitis: Oral: Solution or capsule (100 mg):
Malassezia folliculitis: 200 mg once daily for 1 to 3 weeks (Ref).
Dermatophyte folliculitis (tinea barbae, Majocchi granuloma): 200 mg twice daily for 1 week; repeat 1-week course up to 2 times, each after 2- to 3-week off time (Ref).
Tinea corporis/tinea cruris: Note: For disease that is extensive or refractory to topical therapy.
Oral: Solution or capsule (100 mg): 200 mg once daily for 7 days (Ref).
Tinea pedis/tinea manuum: Note: For disease that is extensive or refractory to topical therapy.
Oral: Solution or capsule (100 mg): 200 mg twice daily for 1 week (Ref).
Tinea versicolor (pityriasis versicolor): Note: For disease that is extensive or refractory to topical therapy (Ref).
Oral: Solution or capsule (100 mg): 200 mg once daily for 5 days (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The 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:
Oral: Initial: No dosage adjustment necessary for any degree of kidney dysfunction; adjust dose based on trough serum concentrations (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2):
Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
Oral: Initial: No dosage adjustment necessary; adjust dose based on trough serum concentrations (Ref).
Hemodialysis, intermittent (thrice weekly): Not dialyzable (Ref):
Oral: Initial: No supplemental dose or dosage adjustment necessary (Ref); adjust dose based on trough serum concentrations.
Peritoneal dialysis: Not dialyzable (Ref):
Oral: Initial: No dosage adjustment necessary (Ref); adjust dose based on trough serum concentrations.
CRRT:
Note: 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) and minimal residual kidney function 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 (eg, cardiac, fluid-related issues) due to drug accumulation is important.
Oral: Initial: No dosage adjustment necessary; adjust dose based on trough concentrations (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration):
Note: 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 (eg, cardiac, fluid-related issues) due to drug accumulation is important.
Oral: Initial: No dosage adjustment necessary; adjust dose based on trough concentrations (Ref).
There are no dosage adjustments provided in the manufacturer's labeling; however, use caution and monitor closely for signs/symptoms of toxicity.
Refer to adult dosing.
(For additional information see "Itraconazole: Pediatric drug information")
Dosage guidance:
Dosage form information: Oral formulations are not interchangeable. Generally, oral solution is the preferred formulation because of improved absorption (Ref). Oral absorption varies between patients and as a result, monitoring of serum concentrations is suggested to ensure adequate and nontoxic levels are achieved (Ref). Capsules are available as two unique formulations (Sporanox [100 mg] and Tolsura [65 mg]) that are not interchangeable; where capsule is an applicable dosage form, dosing is presented for the 100 mg capsule (eg, Sporanox).
Clinical considerations: Initial dosing recommendations presented; for most indications, dosing should be adjusted based on serum concentration monitoring.
General dosing: Limited data available: Infants, Children, and Adolescents: Oral: 5 mg/kg/dose every 12 hours; maximum dose: 100 mg/dose; higher maximum doses may be appropriate for some indications; see indication-specific dosing (Ref).
Allergic bronchopulmonary aspergillosis in patients with cystic fibrosis: Limited data available: Note: Typically recommended only in cases in which there is a poor response to corticosteroids, when corticosteroid toxicity or dependence is present, or for relapsed disease (Ref).
Infants, Children, and Adolescents: Oral: 5 mg/kg/dose every 12 to 24 hours for 3 to 6 months; maximum dose: 200 mg/dose; higher maximum doses may be appropriate based on serum concentrations (Ref).
Blastomycosis, non-CNS infections: Limited data available: Infants, Children, and Adolescents: Oral solution: Oral: 5 mg/kg/dose every 12 hours; maximum dose: 200 mg/dose. Duration should be individualized based on disease severity, site of infection, and response to therapy; usual duration for mild to moderate disease is 6 to 12 months. For severe disease, initial therapy with amphotericin B is recommended for 1 to 2 weeks, followed by 6 to 12 months of itraconazole; ≥12 months of therapy is recommended for bone infections or in patients with immunocompromise (Ref).
Candidiasis: Patients with HIV: Limited data available: Note: Typically reserved as an alternative agent or for fluconazole-refractory disease (Ref).
Oropharyngeal, treatment:
Infants and Children: Oral solution: Oral: 2.5 mg/kg/dose every 12 hours for 7 to 14 days; maximum dose: 100 to 200 mg/dose (Ref).
Adolescents: Oral solution: Oral: 200 mg every 24 hours for 7 to 14 days (Ref).
Esophageal, treatment:
Infants and Children: Oral solution: Oral: 2.5 mg/kg/dose every 12 hours for at least 21 days and at least 2 weeks following resolution of symptoms (Ref).
Adolescents: Oral solution: Oral: 200 mg every 24 hours for 14 to 21 days (Ref).
Vulvovaginal, uncomplicated: Adolescents: Oral solution: Oral: 200 mg every 24 hours for 3 to 7 days (Ref).
Coccidioidomycosis: Limited data available:
Treatment:
Bone and/or joint infection: Note: In some cases (eg, patients with severe disease or HIV), initial therapy should be with an amphotericin B product and then switched to an oral azole. Total duration of therapy depends on clinical response and immune status but is typically ≥1 year (often longer [eg, 3 years or lifetime]) (Ref).
Infants, Children, and Adolescents: Oral: 5 mg/kg/dose every 12 hours. Maximum dose: 200 mg/dose (Ref).
Meningitis: Note: Initiate therapy with an amphotericin B product until clinical improvement, then may switch to a triazole; fluconazole is preferred and itraconazole is considered an alternative option for adolescents; itraconazole is not included in guidelines for infants and children (Ref).
Adolescents with HIV: Oral: 200 mg every 8 to 12 hours; therapy is lifelong due to high relapse rate (Ref).
Pneumonia, focal (mild disease): Patients with HIV: Note: Treatment duration depends on clinical response, typically ≥3 to 6 months (Ref).
Infants, Children, and Adolescents: Oral: 2 to 5 mg/kg/dose every 8 hours for 3 days, followed by 2 to 5 mg/kg/dose every 12 hours; maximum dose: 200 mg/dose (Ref).
Secondary prophylaxis (chronic maintenance therapy) (alternative agent): Patients with HIV: Note: Recommended lifelong for patients with meningitis or disseminated disease; may be considered after milder disease if CD4 count <250 cells/mm3 or CD4 percentage <15% (Ref).
Infants and Children: Oral: 2 to 5 mg/kg/dose twice daily; maximum dose: 200 mg/dose (Ref).
Cryptococcal meningitis: Patients with HIV: Limited data available: Note: Initial induction therapy with amphotericin B and flucytosine is recommended for at least 2 weeks, followed by consolidation therapy and secondary prophylaxis. Fluconazole is preferred for consolidation and secondary prophylaxis, as itraconazole is associated with inferior outcomes. Guidelines no longer recommend itraconazole in adolescent and adult patients; see guidelines for details (Ref).
Consolidation therapy:
Infants and Children: Oral solution (preferred):
Initial load: Oral: 2.5 to 5 mg/kg/dose 3 times daily for 3 days; maximum dose: 200 mg/dose.
Maintenance dose: Oral: 5 to 10 mg/kg/day divided once or twice daily for a minimum of 8 weeks; maximum daily dose: 400 mg/day.
Secondary prophylaxis (chronic maintenance therapy): Infants and Children: Oral solution: Oral: 5 mg/kg/dose every 24 hours; maximum dose: 200 mg/dose. Discontinuation may be considered in patients ≥6 years who have been receiving antiretroviral therapy for ≥3 months and have CD4 cell count ≥100 cells/mm3 and an undetectable viral load.
Histoplasmosis: Limited data available:
Treatment:
Pulmonary, acute primary disease: Note: For severe disease, therapy should be initiated with an amphotericin B product, and then switched to itraconazole (Ref).
Patients with HIV: Infants and Children: Oral solution (preferred): Oral: Initial: 2 to 5 mg/kg/dose every 8 hours for 3 days, followed by 2 to 5 mg/kg/dose every 12 hours for ≥12 months; maximum dose: 200 mg/dose. Treatment duration of 12 weeks may be adequate in children with functional cellular immunity (CD4 percentage >20% or if age ≥6 years, CD4 cell count >300 cells/mm3) if clinically improved and urine antigen concentrations decreased (Ref).
Patients without HIV: Infants, Children, and Adolescents: Oral solution (preferred): Oral: 2.5 to 5 mg/kg/dose every 12 hours for 6 to 12 weeks; maximum dose: 200 mg/dose (Ref).
Disseminated disease: Note: For severe disease, therapy should be initiated with an amphotericin B product, and then transitioned to itraconazole (Ref).
Patients with HIV: Infants, Children, and Adolescents: Oral solution (preferred): Oral: Initial: 2 to 5 mg/kg/dose every 8 hours for 3 days, followed by 2 to 5 mg/kg/dose every 12 hours for ≥12 months; maximum dose: 200 mg/dose (Ref).
Patients without HIV: Infants, Children, and Adolescents: Oral solution (preferred): Oral: 2.5 to 5 mg/kg/dose every 12 hours for ≥3 to 12 months; duration depends on immune status, severity of illness, and clinical response (Ref).
Prophylaxis:
Primary: Adolescents with HIV: Oral: 200 mg once daily (Ref). Note: Only recommended in adolescents with CD4 cell count <150 cells/mm3 who are at high risk due to occupational exposure or residency in a community with hyperendemic histoplasmosis (Ref).
Secondary prophylaxis (chronic maintenance therapy): Note: Not necessary in all patients; see guidelines for details (Ref).
Patients with HIV: Infants, Children, and Adolescents: Oral solution (preferred): Oral: 5 to 10 mg/kg/dose once daily; maximum dose: 200 mg/dose (Ref).
Patients without HIV: Infants, Children, and Adolescents: Oral: 5 mg/kg/dose once daily; maximum dose: 200 mg/dose (Ref).
Microsporidiosis, disseminated disease caused by Trachipleistophora or Anncaliia , treatment: Limited data available:
Adolescents with HIV: Oral: 400 mg once daily in combination with albendazole (Ref).
Sporotrichosis: Limited data available:
Infants, Children, and Adolescents:
Lymphocutaneous or localized cutaneous: Oral solution (preferred): Oral: 3 to 5 mg/kg/dose every 12 hours; maximum dose: 200 mg/dose. Continue for 2 to 4 weeks after all lesions have resolved; usual total duration: 3 to 6 months (Ref).
Step-down therapy, visceral or disseminated (after initial treatment and clinical response with amphotericin B): Oral solution (preferred): Oral: 3 to 5 mg/kg/dose every 12 hours; maximum dose: 200 mg/dose. Continue for ≥12 months (Ref).
Talaromycosis (formerly penicilliosis): Patients with HIV: Limited data available:
Primary prophylaxis: Note: Only recommended for patients residing in or traveling to highly endemic areas in northern Thailand, Vietnam, or Southern China with CD4 cell count <100 cells/mm3 and who are unable to access effective antiretroviral therapy (Ref).
Adolescents: Oral: 200 mg once daily. For residents of highly endemic areas, continue until CD4 count >100 cells/mm3 and virologic suppression with antiretroviral therapy has been sustained for ≥6 months. For travelers, begin prophylaxis 3 days prior to travel and continue through 1 week after leaving the endemic area (Ref).
Treatment (consolidation): Adolescents: Oral: 200 mg every 12 hours for 10 weeks; initiate after completion of amphotericin B induction therapy (Ref).
Secondary prophylaxis (chronic maintenance therapy): Adolescents: Oral: 200 mg once daily. May consider discontinuation when CD4 cell count >100 cells/mm3 and virologic suppression with antiretroviral therapy has been sustained for ≥6 months (Ref).
Tinea capitis (alternative agent): Limited data available:
Continuous regimen: Infants, Children, and Adolescents: Oral: 5 mg/kg/dose once daily; maximum dose: 200 mg/dose (Ref). If using oral solution, some experts recommend a lower dose of 3 mg/kg/dose daily (Ref). Duration of therapy is typically 2 to 6 weeks; up to 12 weeks may be necessary, particularly with Microsporum canis infection (Ref).
Pulse regimen: Infants, Children, and Adolescents: Oral: 5 mg/kg/day once daily for 1 to 3 one-week treatment pulses, with 2 weeks between the first and second pulse and 3 weeks between the second and third pulse. Doses may be divided twice daily for tolerability; maximum daily dose: 400 mg/day. Clinically evaluate scalp after each 1-week pulse to determine need for next pulse (Ref). If using oral solution, a lower dose of 3 mg/kg/dose daily has been recommended by some experts (Ref). A pulse regimen of 1 week of itraconazole treatment per month for 2 to 4 months (ie, 3 weeks off in between pulses) may also be considered (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Nondialyzable. The manufacturer's labeling states to use with caution in patients with renal impairment; dosage adjustment may be needed. In adults, limited data suggest that no dosage adjustments are required in renal impairment; therapeutic drug monitoring should be utilized for dose adjustment (Ref).
There are no dosage adjustments provided in the manufacturer's labeling; however, use caution and monitor closely for signs/symptoms of toxicity.
Itraconazole is associated with cardiovascular effects, including new or worsening hypertension, new or worsening heart failure (HF), prolonged QT interval on ECG , and torsades de pointes (Ref). Cardiovascular effects may result in hospitalization and/or death (Ref). Improvement occurs with treatment and/or discontinuation in most (but not all) cases (Ref).
Mechanism: Dose-related; not clearly established. Proposed mechanisms include mitochondrial dysfunction and negative inotropic effects (Ref).
Onset: Varied; HF reported 1 day to 7 months following initiation (Ref). Torsades de pointes reported a median of 9.5 days (range 1 to 26 days) following initiation (Ref).
Risk factors:
• Higher doses (eg, >400 mg/day) (Ref)
• Hypertension or use of antihypertensives (Ref)
• History of HF or impaired left ventricular function (Ref)
• Cardiovascular disease (Ref)
• Valvular heart disease (Ref)
• Concurrent treatment with other medications known to be associated with QT-prolongation or concurrent interacting medications (Ref)
Azole antifungals, including itraconazole, may cause hepatotoxicity (ranging from mild, asymptomatic increased serum transaminases to hepatic failure) (Ref). Hepatotoxicity is predominantly cholestatic, but cases of hepatocellular damage have also been reported (Ref). If intervention is required, liver injury is generally reversible within ~2 weeks after dose reduction or discontinuation but may recur upon rechallenge (Ref).
Mechanism: Not clearly established; possible mechanisms include inhibition of CYP450 enzymes, leading to decreased metabolism/use of alternative pathways that are more hepatotoxic or a true hypersensitivity reaction (Ref).
Onset: Varied; most cases occur within the first month of therapy (but may occur at any time) (Ref). Most cases occur with long-term, continuous use; rare cases have been reported with prolonged, pulse therapy (>12 weeks) (Ref).
Risk factors:
• Trough concentrations (≥1 mg/L) (Ref)
• Preexisting liver disease (Ref)
• Concurrent hepatotoxic agents and drug interactions (Ref)
• Fungal infection located within the liver (Ref)
• Patients of Japanese descent may be more at risk, secondary to higher prevalence of CYP2C19 genetic polymorphisms (Ref)
• Cross-reactivity among oral azole antifungals has not been consistently reported in patients with histories of hepatotoxicity (Ref)
Immediate hypersensitivity reactions have been reported and include urticaria , angioedema, anaphylaxis , and anaphylactic shock (Ref). Delayed hypersensitivity reactions have also been reported and range from an erythematous rash or morbilliform rash (Ref) to severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP) (Ref). Other delayed hypersensitivity reactions include serum sickness-like reaction (Ref), fixed drug eruption (Ref), skin photosensitivity (Ref) and symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) (Ref).
Mechanism: Non–dose-related; immunologic. Immediate hypersensitivity reactions (eg, anaphylaxis, urticaria) are IgE-mediated. Delayed hypersensitivity reactions, including rash and SCARs, are 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); anaphylactic shock has been reported after 2 weeks of itraconazole treatment (Ref). Delayed hypersensitivity reactions: Non-specific rash: Intermediate; occur within a week after initiation (Ref). Other reactions (including SCARs): Varied; occur after 7 to 14 days up to 3 months (Ref); in some patients, may occur within 24 hours after completion of treatment (Ref).
Risk factors:
• Cross-reactivity: Cross-reactivity among oral azole antifungals has not been consistently reported (Ref). Possible cross-reactivity between fluconazole and itraconazole has been suggested (Ref). However, lack of cross-reactivity has been documented between itraconazole and fluconazole, as well as between itraconazole and ketoconazole (Ref). In addition, no cross-reactivity was noted between itraconazole and voriconazole (Ref).
Itraconazole is associated with metabolic-related adverse reactions, including hypokalemia , hypertension, and pseudoaldosteronism (Ref). Metabolic-related adverse reactions are often considered class-related effects, more often observed with itraconazole and posaconazole (Ref). Resolution occurs following discontinuation (Ref).
Mechanism: Possibly dose-related; hypothesized to occur primarily due to cortisol-induced mineralocorticoid receptor activation due to 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enzyme inhibition (Ref).
Onset: Varied; generally within first 2 weeks of therapy but may occur later (Ref).
Risk factors:
• Higher doses (eg, 600 mg total daily dose) (Ref)
• Concurrent exposure to steroids (Ref)
Itraconazole is associated with peripheral neuropathy, which often presents as bilateral polyneuropathy of the hands and feet (Ref). Itraconazole-associated peripheral neuropathy appears to be more common than posaconazole or voriconazole-associated neuropathy (Ref). Symptoms often resolve following discontinuation (Ref).
Mechanism: Unknown; hypothesized to be caused by the azole moiety (Ref).
Onset: Varied; median 3 months (range 1 to 18 months) (Ref).
Risk factors:
• Concurrent calcineurin inhibitors, vinca alkaloids or other drug interactions (Ref)
Other possible risk factors:
• Higher drug concentrations, although may occur in patients with drug concentrations within the therapeutic range (Ref)
• Long-term therapy (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Gastrointestinal: Nausea (3% to 11%)
1% to 10%:
Cardiovascular: Chest pain (3%), edema (4%), hypertension (3%)
Dermatologic: Diaphoresis (4%), pruritus (3% to 5%), skin rash (3% to 9%)
Endocrine & metabolic: Adrenocortical insufficiency (<2%), albuminuria (1%), decreased libido (1%), dehydration (<2%), gynecomastia (<2%), hot flash (<2%), hypertriglyceridemia (3%), hypokalemia (2%), weight loss (<2%)
Gastrointestinal: Abdominal pain (2% to 4%), anorexia (1%), aphthous stomatitis (3%), constipation (2% to 3%), diarrhea (3% to 10%), dysgeusia (<2%), dyspepsia (3% to 4%), dysphagia (<2%), flatulence (4%), gastritis (2%), gastroenteritis (2%), gingivitis (3%), hemorrhoids (<2%), increased appetite (2%), vomiting (5% to 6%)
Genitourinary: Cystitis (3%), erectile dysfunction (1%), hematuria (<2%), mastalgia (male: <2%), urinary tract infection (3%)
Hepatic: Abnormal liver function (3%)
Infection: Herpes zoster (2%), infection (<2%)
Nervous system: Abnormal dreams (2%), anxiety (3%), asthenia (2%), depression (1% to 3%), dizziness (2% to 4%), drowsiness (1%), fatigue (1% to 3%), headache (4% to 10%), insomnia (<2%), malaise (1% to 3%), pain (2% to 3%), rigors (<2%), tremor (2%)
Neuromuscular & skeletal: Back pain (<2%), bursitis (3%), myalgia (3%)
Ophthalmic: Visual disturbance (<2%)
Otic: Tinnitus (<2%)
Respiratory: Cough (4%), dyspnea (3%), increased bronchial secretions (3%), pharyngitis (2%), pneumonia (2%), pneumonia due to Pneumocystis jirovecii (2%), rhinitis (5% to 9%), sinusitis (2% to 7%), upper respiratory tract infection (8%)
Miscellaneous: Fever (2% to 6%)
<1%: Endocrine & metabolic: Menstrual disease
Frequency not defined:
Cardiovascular: Hypotension, orthostatic hypotension, tachycardia, vasculitis
Dermatologic: Hyperhidrosis
Endocrine & metabolic: Hyperglycemia, hyperkalemia, hypomagnesemia, increased lactate dehydrogenase
Hepatic: Hyperbilirubinemia, increased gamma-glutamyl transferase, increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, jaundice
Hypersensitivity: Facial edema
Nervous system: Chills, confusion, vertigo, voice disorder
Renal: Increased blood urea nitrogen, kidney insufficiency
Postmarketing:
Cardiovascular: Heart failure (including worsening of heart failure) (Tsang 2022), peripheral edema, prolonged QT interval on ECG (Salem 2017), torsades de pointes (Salem 2017)
Dermatologic: Acute generalized exanthematous pustulosis (Cancado 2009), alopecia, erythema multiforme, erythematous rash (Goto 2000), exfoliative dermatitis, fixed drug eruption (Gupta 2008), morbilliform rash (Kramer 1997), skin photosensitivity (Alvarez-Fernandez 2000), Stevens-Johnson syndrome (Das 2020), toxic epidermal necrolysis (Das 2020), urticaria (Martinez-Alonso 2003)
Endocrine & metabolic: Pseudoaldosteronism (Beck 2020)
Gastrointestinal: Pancreatitis
Genitourinary: Pollakiuria, urinary incontinence
Hematologic & oncologic: Leukopenia, neutropenia, thrombocytopenia
Hepatic: Hepatic failure (Pettit 2016), hepatitis, hepatotoxicity
Hypersensitivity: Anaphylactic shock (Chen 2009), anaphylaxis (Chen 2009), angioedema (Martinez-Alonso 2003), hypersensitivity angiitis, nonimmune anaphylaxis, serum sickness, serum sickness-like reaction (Park 1998)
Nervous system: Hypoesthesia, paresthesia, peripheral neuropathy (Baxter 2011)
Neuromuscular & skeletal: Arthralgia, increased creatine phosphokinase in blood specimen
Ophthalmic: Blurred vision, diplopia
Otic: Hearing loss
Respiratory: Pulmonary edema
Hypersensitivity to itraconazole or any component of the formulation; concurrent administration with avanafil, cisapride, disopyramide, dofetilide, dronedarone, eplerenone, ergot derivatives, felodipine, finerenone, irinotecan, isavuconazole, ivabradine, lomitapide, lovastatin, lurasidone, methadone, midazolam (oral), naloxegol, nisoldipine, pimozide, quinidine, ranolazine, simvastatin, ticagrelor, triazolam, or voclosporin; concurrent administration with colchicine, fesoterodine, or solifenacin in patients with varying degrees of renal or hepatic impairment; coadministration with eliglustat in patients who are poor or intermediate metabolizers of CYP2D6 and in patients taking strong or moderate CYP2D6 inhibitors; coadministration with venetoclax in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma during the dose initiation and ramp-up phase of venetoclax; treatment of onychomycosis (or other non-life-threatening indications) in patients with evidence of ventricular dysfunction, such as congestive heart failure (CHF) or a history of CHF; treatment of onychomycosis in women who are pregnant or contemplating pregnancy.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Concurrent administration with apixaban, asunaprevir, domperidone, eletriptan, fesoterodine in patients with moderate to severe renal or hepatic impairment, rivaroxaban, or solifenacin in patients with severe renal impairment or moderate to severe hepatic impairment (capsule, oral solution); treatment of dermatomycosis (tinea pedis, tinea cruris, tinea corporis, tinea versicolor [pityriasis versicolor]) in women who are pregnant or intend to become pregnant (capsule).
Concerns 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).
• Hearing loss: Transient or permanent hearing loss has been reported. Quinidine (a contraindicated drug) was used concurrently in several of these cases. Hearing loss usually resolves after discontinuation, but may persist in some patients.
Disease-related concerns:
• Cystic fibrosis: Large differences in itraconazole pharmacokinetic parameters have been observed in cystic fibrosis patients receiving the oral solution; if a patient with cystic fibrosis does not respond to therapy, alternate therapies should be considered.
• Hepatic impairment: Use with caution in patients with hepatic impairment; monitor liver function closely. Not recommended for use in patients with active liver disease, elevated liver enzymes, or prior hepatotoxic reactions to other drugs unless the expected benefit exceeds the risk of hepatotoxicity.
• Onychomycosis: [US Boxed Warning]: Use is contraindicated for treatment of onychomycosis in patients with ventricular dysfunction such as heart failure (HF) or a history of HF. Cases of HF, peripheral edema, and pulmonary edema have occurred in this patient population. The manufacturer recommends confirmation of diagnosis testing of nail specimens prior to treatment of onychomycosis.
• Renal impairment: Use with caution in patients with renal impairment; limited information is available; dosage adjustment may be needed.
Dosage form specific issues:
• Oral capsules (100 mg [Sporanox]): Absorption of itraconazole capsules is reduced when gastric acidity is reduced (eg, achlorhydria, acid suppressive therapy); administer with an acidic beverage (eg, non-diet cola) in patients with reduced gastric acidity and separate administration from acid suppressive therapy (refer to drug interactions section). Monitor for response.
• Oral capsules (65 mg [Tolsura]): Absorption of itraconazole capsules is increased when gastric acidity is reduced (eg, acid suppressive therapy). Monitor for adverse reactions; itraconazole dose reduction may be necessary.
• Oral solution: Only the oral solution has proven efficacy in oral/esophageal candidiasis; mucosal exposure may vary between the oral solution and capsules. Initiation of treatment with oral solution is not recommended in patients at immediate risk for systemic candidiasis (eg, patients with severe neutropenia). Oral solution contains the excipient cyclodextrin.
• Product interchangeability: Due to differences in bioavailability, formulations cannot be used interchangeably .
• 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 1997; Zar 2007).
Other warnings/precautions:
• Appropriate use: Itraconazole should NOT be used for voriconazole-refractory aspergillosis because the same antifungal and/or resistance mechanism(s) may be shared by both agents.
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).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Sporanox: 100 mg [contains corn starch, d&c red #22 (eosine), fd&c blue #1 (brilliant blue), fd&c blue #2 (indigotine,indigo carmine)]
Sporanox Pulsepak: 100 mg [DSC] [contains corn starch, d&c red #22 (eosine), fd&c blue #1 (brilliant blue), fd&c blue #2 (indigotine,indigo carmine)]
Tolsura: 65 mg
Generic: 100 mg
Solution, Oral:
Sporanox: 10 mg/mL (150 mL) [contains hydroxypropyl-beta-cyclodextrin, propylene glycol, saccharin sodium]
Generic: 10 mg/mL (10 mL, 150 mL)
Yes
Capsules (Itraconazole Oral)
100 mg (per each): $8.68 - $24.15
Capsules (Sporanox Oral)
100 mg (per each): $33.78
Solution (Itraconazole Oral)
10 mg/mL (per mL): $2.31 - $2.47
Solution (Sporanox Oral)
10 mg/mL (per mL): $2.74
Disclaimer: 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 reimbursement 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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Sporanox: 100 mg [contains d&c red #22 (eosine), fd&c blue #1 (brilliant blue), fd&c blue #2 (indigotine,indigo carmine)]
Generic: 100 mg
Solution, Oral:
Sporanox: 10 mg/mL ([DSC]) [contains hydroxypropyl-beta-cyclodextrin, propylene glycol, saccharin sodium]
Generic: 10 mg/mL (150 mL)
Oral: Formulations are not interchangeable; generally, oral solution is the preferred formulation because of improved absorption (Ref). Administer capsule with a full meal. Oral solution should be taken on an empty stomach; when treating oropharyngeal and esophageal candidiasis, solution should be swished vigorously in mouth (10 mL at a time), then swallowed. Swallow capsule whole; do not crush, chew, or break.
Oral: Capsule and oral solution formulations are not bioequivalent and thus are not interchangeable; generally, oral solution is the preferred formulation because of improved absorption (Ref).
Capsule: Absorption is best if taken with food; therefore, it is best to administer after a full meal. Capsules should be swallowed whole.
Solution: Should be taken on an empty stomach. When treating oropharyngeal and esophageal candidiasis, solution should be swished vigorously in mouth, then swallowed.
Aspergillosis (65 mg and 100 mg capsules): Treatment of pulmonary and extrapulmonary aspergillosis in immunocompromised and nonimmunocompromised patients who are intolerant of or refractory to amphotericin B therapy. Note: IDSA aspergillosis guidelines recommend amphotericin B formulations for invasive aspergillosis (initial or salvage) only when voriconazole is contraindicated or not tolerated (IDSA [Patterson 2016]).
Blastomycosis (65 mg and 100 mg capsules): Treatment of pulmonary and extrapulmonary blastomycosis in immunocompromised and nonimmunocompromised patients.
Candidiasis, esophageal and oropharyngeal (oral solution): Treatment of oropharyngeal and esophageal candidiasis.
Histoplasmosis (65 mg and 100 mg capsules): Treatment of histoplasmosis, including chronic cavitary pulmonary disease and disseminated, nonmeningeal histoplasmosis in immunocompromised and nonimmunocompromised patients.
Onychomycosis:
Capsules (100 mg): Treatment of onychomycosis of the toenail, with or without fingernail involvement, and onychomycosis of the fingernail caused by dermatophytes (tinea unguium) in nonimmunocompromised patients.
Candidiasis, vulvovaginal in patients with HIV; Coccidioidomycosis; Paracoccidioidomycosis; Prophylaxis against invasive fungal infections; Sporotrichosis; Talaromycosis (formerly penicilliosis); Tinea infections
Itraconazole may be confused with fluconazole, posaconazole, voriconazole
Sporanox may be confused with Suprax, Topamax
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.
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (strong), P-glycoprotein/ABCB1
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 program by clicking on the “Launch drug interactions program” link above.
Abemaciclib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Abemaciclib. Management: In patients taking abemaciclib at a dose of 200 mg or 150 mg twice daily, reduce the dose to 100 mg twice daily when combined with strong CYP3A4 inhibitors. In patients taking abemaciclib 100 mg twice daily, decrease the dose to 50 mg twice daily. Risk D: Consider therapy modification
Acalabrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Acalabrutinib. Risk X: Avoid combination
Adagrasib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Adagrasib. Management: Avoid use of adagrasib and strong CYP3A4 inhibitors until adagrasib concentrations have reached steady state (ie, after approximately 8 days of therapy). Risk D: Consider therapy modification
Ado-Trastuzumab Emtansine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ado-Trastuzumab Emtansine. Specifically, strong CYP3A4 inhibitors may increase concentrations of the cytotoxic DM1 component. Management: Avoid concomitant use of ado-trastuzumab emtansine and strong CYP3A4 inhibitors when possible. Consider alternatives that do not inhibit CYP3A4 or consider administering after CYP3A4 inhibitor discontinuation. Monitor for toxicities if combined. Risk D: Consider therapy modification
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider therapy modification
ALfentanil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ALfentanil. Management: If use of alfentanil and strong 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 modification
Alfuzosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. Risk X: Avoid combination
Aliskiren: Itraconazole may increase the serum concentration of Aliskiren. Risk X: Avoid combination
Alitretinoin (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alitretinoin (Systemic). Management: Consider reducing the alitretinoin dose to 10 mg when used together with strong CYP3A4 inhibitors. Monitor for increased alitretinoin effects/toxicities if combined with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Almotriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Almotriptan. Management: Limit initial almotriptan dose to 6.25 mg and maximum dose to 12.5 mg in any 24-period when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Risk D: Consider therapy modification
Alosetron: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron. Risk C: Monitor therapy
ALPRAZolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ALPRAZolam. Risk X: Avoid combination
Amiodarone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Amiodarone. Management: Consider alternatives to use of amiodarone and strong CYP3A4 inhibitors. If combined, monitor for increased amiodarone concentrations and toxicities. Risk D: Consider therapy modification
AmLODIPine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of AmLODIPine. Risk C: Monitor therapy
Antacids: May decrease the serum concentration of Itraconazole. Antacids may increase the serum concentration of Itraconazole. Management: Administer Sporanox brand itraconazole at least 2 hours before or 2 hours after administration of any antacids. Exposure to Tolsura brand itraconazole may be increased by antacids; consider itraconazole dose reduction. Risk D: Consider therapy modification
Apixaban: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Apixaban. Management: US labeling recommends a 50% apixaban dose reduction in patients who would otherwise receive 5 or 10 mg twice daily, and avoiding in patients who would otherwise receive 2.5 mg twice daily. Canadian labeling lists any combined use as contraindicated. Risk D: Consider therapy modification
Aprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Aprepitant. Risk X: Avoid combination
ARIPiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions are required for indications other than major depressive disorder. Dose reductions vary based on formulation, initial starting dose, CYP2D6 genotype, and use of CYP2D6 inhibitors. See full interaction monograph for details. Risk D: Consider therapy modification
ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Decrease aripiprazole lauroxil dose to next lower strength if used with strong CYP3A4 inhibitors for over 14 days. No dose adjustment needed if using the lowest dose (441 mg). Max dose is 441 mg in CYP2D6 PMs or if also taking strong CYP2D6 inhibitors. Risk D: Consider therapy modification
Artemether and Lumefantrine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Artemether and Lumefantrine. Risk C: Monitor therapy
Asciminib: Itraconazole may decrease the serum concentration of Asciminib. Specifically, the hydroxypropyl-beta-cyclodextrin contained in oral itraconazole solution may decrease asciminib concentrations. Risk X: Avoid combination
Astemizole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Astemizole. Risk X: Avoid combination
Asunaprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Asunaprevir. Risk X: Avoid combination
Atazanavir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Atazanavir. Risk C: Monitor therapy
Atogepant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended atogepant dose is 10 mg once daily with a concurrent strong CYP3A4 inhibitor. If used for treatment of chronic migraine, concurrent use of atogepant with strong CYP3A4 inhibitors should be avoided. Risk D: Consider therapy modification
Atorvastatin: Itraconazole may increase the serum concentration of Atorvastatin. Management: Limit atorvastatin to a maximum adult dose of 20 mg/day in patients receiving itraconazole. Assess clinical response to ensure that the lowest necessary dose of atorvastatin is used. Consider use of fluva-, rosuva-, pitava-, or pravastatin when possible. Risk D: Consider therapy modification
Avacopan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avacopan. Management: Decrease the avacopan dose to 30 mg once daily during coadministration with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Avanafil: Itraconazole may increase the serum concentration of Avanafil. Risk X: Avoid combination
Avapritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avapritinib. Risk X: Avoid combination
Axitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib. Management: Avoid concurrent use of axitinib with any strong CYP3A inhibitor whenever possible. If a strong CYP3A inhibitor must be used with axitinib, a 50% axitinib dose reduction is recommended. Risk D: Consider therapy modification
Barnidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Barnidipine. Risk X: Avoid combination
Beclomethasone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Beclomethasone (Systemic). Risk C: Monitor therapy
Bedaquiline: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Bedaquiline. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bedaquiline. Management: Limit duration of concurrent use of bedaquiline with strong CYP3A4 inhibitors to no more than 14 days, unless the benefit of continued use outweighs the possible risks. Monitor for toxic effects of bedaquiline, including QTc interval prolongation. Risk D: Consider therapy modification
Benidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benidipine. Risk C: Monitor therapy
Benperidol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benperidol. Risk C: Monitor therapy
Benzhydrocodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Risk C: Monitor therapy
Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification
Betamethasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Nasal). Risk C: Monitor therapy
Betamethasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Ophthalmic). Risk C: Monitor therapy
Betamethasone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Systemic). Risk C: Monitor therapy
Betamethasone (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Topical). Risk C: Monitor therapy
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination
Blonanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Blonanserin. Risk X: Avoid combination
Bortezomib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bortezomib. Risk C: Monitor therapy
Bosentan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosentan. Risk C: Monitor therapy
Bosutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosutinib. Risk X: Avoid combination
Brentuximab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor therapy
Brexpiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose 50% with strong CYP3A4 inhibitors; reduce to 25% of usual if used with both a strong CYP3A4 inhibitor and a CYP2D6 inhibitor in patients not being treated for MDD, or strong CYP3A4 inhibitor used in a CYP2D6 poor metabolizer. Risk D: Consider therapy modification
Brigatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with strong CYP3A4 inhibitors when possible. If combination cannot be avoided, reduce the brigatinib dose by approximately 50%, rounding to the nearest tablet strength (ie, from 180 mg to 90 mg, or from 90 mg to 60 mg). Risk D: Consider therapy modification
Bromocriptine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bromocriptine. Management: Consider alternatives to the use of bromocriptine with strong CYP3A4 inhibitors. If combined, monitor closely for increased bromocriptine toxicities and consider bromocriptine dose reductions. Risk D: Consider therapy modification
Bromperidol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bromperidol. Risk C: Monitor therapy
Brotizolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brotizolam. Risk C: Monitor therapy
Budesonide (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Nasal). Risk C: Monitor therapy
Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Oral Inhalation). Management: Consider alternatives to this combination when possible. If combined, monitor for increased corticosteroid adverse effects during coadministration of inhaled budesonide and strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Budesonide (Systemic): CYP3A4 Inhibitors (Strong) 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 a strong CYP3A4 inhibitor, they should be closely monitored for signs and symptoms of corticosteroid excess. Risk D: Consider therapy modification
Budesonide (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Topical). Risk X: Avoid combination
Buprenorphine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Buprenorphine. Risk C: Monitor therapy
BusPIRone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of BusPIRone. Management: Limit the buspirone dose to 2.5 mg daily and monitor patients for increased buspirone effects/toxicities if combined with strong CYP3A4 inhibitors. Dose adjustments of buspirone or a strong CYP3A4 inhibitor should be based on clinical assessment. Risk D: Consider therapy modification
Busulfan: Itraconazole may increase the serum concentration of Busulfan. Risk C: Monitor therapy
Butorphanol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Butorphanol. Risk C: Monitor therapy
Cabazitaxel: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cabazitaxel. Management: Concurrent use of cabazitaxel with strong inhibitors of CYP3A4 should be avoided when possible. If such a combination must be used, consider a 25% reduction in the cabazitaxel dose. Risk D: Consider therapy modification
Cabozantinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cabozantinib. Management: Avoid use of a strong CYP3A4 inhibitor with cabozantinib if possible. If combined, decrease cabozantinib capsules (Cometriq) by 40 mg from previous dose or decrease cabozantinib tablets (Cabometyx) by 20 mg from previous dose. Risk D: Consider therapy modification
Calcifediol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Calcifediol. Risk C: Monitor therapy
Calcitriol (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Calcitriol (Systemic). Risk C: Monitor therapy
Cannabidiol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabidiol. Risk C: Monitor therapy
Cannabis: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor therapy
Capivasertib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Capivasertib. Management: Avoid concomitant use of capivasertib with strong CYP3A4 inhibitors when possible. If combined, reduce the capivasertib dose to 320 mg twice daily for 4 days, followed by 3 days off. Monitor patients closely for adverse reactions. Risk D: Consider therapy modification
Capmatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Capmatinib. Risk C: Monitor therapy
Cardiac Glycosides: Itraconazole may increase the serum concentration of Cardiac Glycosides. Management: Measure cardiac glycoside serum concentrations before initiating treatment with itraconazole. Reduce cardiac glycoside concentrations by either reducing the dose by 30% to 50% or by modifying the dosing frequency. Risk D: Consider therapy modification
Cariprazine: CYP3A4 Inhibitors (Strong) 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 (Strong) may increase the serum concentration of Cariprazine. Management: Decrease cariprazine dose 50% (4.5 mg to 1.5 mg or 3 mg; 1.5 mg to 1.5 mg every other day) if starting a strong CYP3A4 inhibitor. If on a strong CYP3A4 inhibitor, start cariprazine at 1.5 mg day 1, 0 mg day 2, then 1.5 mg daily. May increase to 3 mg daily Risk D: Consider therapy modification
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: Monitor therapy
Ceritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ceritinib. Management: Avoid this combination whenever possible. If combined, the ceritinib dose should be reduced by approximately one-third (to the nearest 150 mg). Resume the prior ceritinib dose after cessation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification
ChlordiazePOXIDE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ChlordiazePOXIDE. Risk C: Monitor therapy
Ciclesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ciclesonide (Oral Inhalation). Risk C: Monitor therapy
Cilnidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilnidipine. Risk C: Monitor therapy
Cilostazol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilostazol. Management: Decrease the dose of cilostazol to 50 mg twice daily when combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Cinacalcet: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cinacalcet. Risk C: Monitor therapy
Cisapride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cisapride. Risk X: Avoid combination
Clarithromycin: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Clarithromycin. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Clarithromycin. Risk C: Monitor therapy
Clindamycin (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Clindamycin (Systemic). Risk C: Monitor therapy
Clobetasone: Itraconazole may increase the serum concentration of Clobetasone. Risk X: Avoid combination
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
ClonazePAM: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ClonazePAM. Risk C: Monitor therapy
CloZAPine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
Cobicistat: Itraconazole may increase the serum concentration of Cobicistat. Cobicistat may increase the serum concentration of Itraconazole. Management: Limit itraconazole to a maximum adult dose of 200 mg/day in patients treated with the elvitegravir/cobicistat/emtricitabine/tenofovir combination products. Dosing recommendations for other cobicistat-containing products are not available. Risk D: Consider therapy modification
Cobimetinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cobimetinib. Risk X: Avoid combination
Codeine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Codeine. Risk C: Monitor therapy
Colchicine: Itraconazole may increase the serum concentration of Colchicine. Management: Colchicine is contraindicated during and for 2 weeks after itraconazole in patients with impaired renal or hepatic function. In those with normal renal and hepatic function, reduce colchicine dose as directed. See interaction monograph for details. Risk D: Consider therapy modification
Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Conivaptan. Risk X: Avoid combination
Copanlisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Copanlisib. Management: If concomitant use of copanlisib and strong CYP3A4 inhibitors cannot be avoided, reduce the copanlisib dose to 45 mg. Monitor patients for increased copanlisib effects/toxicities. Risk D: Consider therapy modification
Cortisone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cortisone. Risk C: Monitor therapy
Crizotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Crizotinib. Management: Avoid concomitant use of crizotinib and strong CYP3A4 inhibitors whenever possible. If combined use cannot be avoided, crizotinib dose reductions are required, which vary according to indication. See full interaction monograph for details. Risk D: Consider therapy modification
CycloPHOSphamide: Itraconazole may enhance the adverse/toxic effect of CycloPHOSphamide. Specifically, serum creatinine and serum bilirubin may be increased. Itraconazole may increase the serum concentration of CycloPHOSphamide. Risk C: Monitor therapy
CycloSPORINE (Systemic): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of CycloSPORINE (Systemic). Fluconazole and isavuconazonium considerations are addressed in separate monographs. Management: Consider reducing cyclosporine doses by 50% to 80% during coadministration with ketoconazole, 50% with voriconazole or itraconazole, and 25% with posaconazole. Cyclosporine dose reductions may be required with other azoles. Risk D: Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease serum concentrations of the active metabolite(s) of Itraconazole. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Itraconazole. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease serum concentrations of the active metabolite(s) of Itraconazole. CYP3A4 Inducers (Strong) may decrease the serum concentration of Itraconazole. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Itraconazole. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Itraconazole. Risk C: Monitor therapy
Cyproterone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cyproterone. Risk C: Monitor therapy
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy
Dabrafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dabrafenib. Management: Consider alternatives to any strong CYP3A4 inhibitor for patients being treated with dabrafenib. If such a combination cannot be avoided, monitor closely for evidence of dabrafenib-related adverse effects. Risk D: Consider therapy modification
Daclatasvir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Daclatasvir. Management: Decrease the daclatasvir dose to 30 mg once daily if combined with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Dapoxetine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dapoxetine. Risk X: Avoid combination
Daridorexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Daridorexant. Risk X: Avoid combination
Darifenacin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Darifenacin. Management: Limit the darifenacin dose to no more than 7.5 mg daily if combined with strong CYP3A4 inhibitors. Monitor patients for increased darifenacin toxicities (eg, dry mouth, constipation, headache, CNS effects) when these agents are combined. Risk D: Consider therapy modification
Darolutamide: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Darolutamide. Risk C: Monitor therapy
Darunavir: May increase the serum concentration of Itraconazole. Itraconazole may increase the serum concentration of Darunavir. Management: Limit the adult maximum itraconazole dose to 200 mg/day in patients receiving darunavir/ritonavir and monitor for increased itraconazole adverse effects during coadministration. Risk D: Consider therapy modification
Dasatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dasatinib. Management: This combination should be avoided if possible. If combined, decrease dasatinib dose from 140 mg to 40 mg, 100 mg to 20 mg, or 70 mg to 20 mg. For patients taking 60 mg or 40 mg daily, stop dasatinib until the CYP3A4 inhibitor is discontinued. Risk D: Consider therapy modification
Deflazacort: CYP3A4 Inhibitors (Strong) 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 modification
Delamanid: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Delamanid. Management: Increase ECG monitoring frequency if delamanid is combined with strong CYP3A4 inhibitors due to the risk for QTc interval prolongation. Continue frequent ECG assessments throughout full delamanid treatment period. Risk D: Consider therapy modification
DexAMETHasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of DexAMETHasone (Ophthalmic). Risk C: Monitor therapy
DexAMETHasone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapy
DiazePAM: CYP3A4 Inhibitors (Strong) may increase the serum concentration of DiazePAM. Risk C: Monitor therapy
Dichlorphenamide: Antifungal Agents (Azole Derivatives, Systemic) may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Didanosine: May decrease the serum concentration of Itraconazole. Management: Administer itraconazole at least 2 hours prior to buffered didanosine. This interaction is not expected with enteric-coated didanosine capsules since they do not contain buffering agents. Risk D: Consider therapy modification
Dienogest: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dienogest. Risk C: Monitor therapy
DilTIAZem: CYP3A4 Inhibitors (Strong) may increase the serum concentration of DilTIAZem. Risk C: Monitor therapy
Disopyramide: Itraconazole may increase the serum concentration of Disopyramide. Risk X: Avoid combination
DOCEtaxel: CYP3A4 Inhibitors (Strong) may increase the serum concentration of DOCEtaxel. Management: Avoid the concomitant use of docetaxel and strong CYP3A4 inhibitors when possible. If combined use is unavoidable, consider a 50% docetaxel dose reduction and monitor for increased docetaxel toxicities. Risk D: Consider therapy modification
Dofetilide: Itraconazole may increase the serum concentration of Dofetilide. Risk X: Avoid combination
Domperidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Domperidone. Risk X: Avoid combination
Doxazosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Doxazosin. Risk C: Monitor therapy
Doxercalciferol: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Doxercalciferol. Risk C: Monitor therapy
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy
DroNABinol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of DroNABinol. Risk C: Monitor therapy
Dronedarone: Itraconazole may increase the serum concentration of Dronedarone. Risk X: Avoid combination
Dutasteride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride. Risk C: Monitor therapy
Duvelisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Duvelisib. Management: Reduce the dose of duvelisib to 15 mg twice a day when used together with a strong CYP3A4 inhibitor. Monitor closely for evidence of altered response to treatment. Risk D: Consider therapy modification
Dydrogesterone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dydrogesterone. Risk C: Monitor therapy
Ebastine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ebastine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ebastine. Risk C: Monitor therapy
Edoxaban: Itraconazole may increase the serum concentration of Edoxaban. Management: In patients treated for DVT/PE, reduce the edoxaban dose to 30 mg daily when combined with itraconazole. No dose adjustment is recommended for patients treated for atrial fibrillation. Monitor for increased edoxaban toxicities (ie, bleeding) when combined Risk D: Consider therapy modification
Efavirenz: May decrease serum concentrations of the active metabolite(s) of Itraconazole. Efavirenz may decrease the serum concentration of Itraconazole. Risk X: Avoid combination
Efonidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Efonidipine. Risk C: Monitor therapy
Elacestrant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elacestrant. Risk X: Avoid combination
Elagolix: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elagolix. Management: Use of the elagolix 200 mg twice daily dose with a strong CYP3A4 inhibitor for longer than 1 month is not recommended. Limit combined use of the elagolix 150 mg once daily dose with a strong CYP3A4 inhibitor to a maximum of 6 months. Risk D: Consider therapy modification
Elagolix, Estradiol, and Norethindrone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Elagolix, Estradiol, and Norethindrone may decrease the serum concentration of CYP3A4 Inhibitors (Strong). Specifically, concentrations of strong CYP3A4 inhibitors that are also CYP3A4 substrates may be decreased. Risk X: Avoid combination
Elbasvir and Grazoprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elbasvir and Grazoprevir. Management: Consider alternatives to this combination when possible. If combined, monitor for increased elbasvir/grazoprevir toxicities, including ALT elevations. Risk D: Consider therapy modification
Eletriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eletriptan. Risk X: Avoid combination
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: Administer elexacaftor/tezacaftor/ivacaftor in the morning, twice a week, 3 to 4 days apart, with no evening doses of ivacaftor alone. Specific dosing varies by age and weight. See full monograph for details. Risk D: Consider therapy modification
Eliglustat: Itraconazole may increase the serum concentration of Eliglustat. Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with itraconazole. Use of eliglustat is contraindicated during and for 2 weeks after itraconazole in CYP2D6 IMs, PMs, or in CYP2D6 EMs who are also taking strong or moderate CYP2D6 inhibitors. Risk D: Consider therapy modification
Enasidenib: May decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Risk X: Avoid combination
Enfortumab Vedotin: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Enfortumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor therapy
Entrectinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Entrectinib. Management: Avoid strong CYP3A4 inhibitors if possible. If needed, reduce entrectinib dose to 50 mg on alternating days if starting dose 200 mg; to 50 mg/day if starting dose 300 mg or 400 mg; to 100 mg/day if starting dose 600 mg. Risk D: Consider therapy modification
Eplerenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone. Risk X: Avoid combination
Erdafitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erdafitinib. Management: Avoid concomitant use of erdafitinib and strong CYP3A4 inhibitors when possible. If combined, monitor closely for erdafitinib adverse reactions and consider dose modifications accordingly. Risk D: Consider therapy modification
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Erlotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erlotinib. Management: Avoid use of this combination when possible. When the combination must be used, monitor the patient closely for the development of erlotinib-associated adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). Risk D: Consider therapy modification
Erythromycin (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erythromycin (Systemic). Management: Consider alternatives to this combination when possible. If combined, monitor for increased erythromycin effects and toxicities, including QTc interval prolongation. Risk D: Consider therapy modification
Estazolam: Itraconazole may increase the serum concentration of Estazolam. Risk X: Avoid combination
Estrogen Derivatives: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy
Eszopiclone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eszopiclone. Management: Limit the eszopiclone dose to 2 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased eszopiclone effects and toxicities (eg, somnolence, drowsiness, CNS depression). Risk D: Consider therapy modification
Etizolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Etizolam. Risk C: Monitor therapy
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Risk C: Monitor therapy
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy
Etravirine: Itraconazole may increase the serum concentration of Etravirine. Etravirine may decrease the serum concentration of Itraconazole. Risk C: Monitor therapy
Everolimus: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Everolimus. Risk X: Avoid combination
Evogliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Evogliptin. Risk C: Monitor therapy
Fedratinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fedratinib. Management: Consider alternatives when possible. If used together, decrease fedratinib dose to 200 mg/day. After the inhibitor is stopped, increase fedratinib to 300 mg/day for the first 2 weeks and then to 400 mg/day as tolerated. Risk D: Consider therapy modification
Felodipine: Itraconazole may increase the serum concentration of Felodipine. Risk X: Avoid combination
FentaNYL: CYP3A4 Inhibitors (Strong) may increase the serum concentration of FentaNYL. Management: Consider fentanyl dose reductions when combined with a strong 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 modification
Fesoterodine: Itraconazole may increase serum concentrations of the active metabolite(s) of Fesoterodine. Management: Limit fesoterodine doses to 4 mg daily when combined with itraconazole. Use of fesoterodine with itraconazole, or for 2 weeks after itraconazole discontinuation, in patients with moderate to severe hepatic or renal impairment is contraindicated. Risk D: Consider therapy modification
Fexinidazole: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Fexinidazole. Management: Avoid use of fexinidazole and strong CYP3A4 inhibitors when possible. If combined, monitor for reduced fexinidazole efficacy. Risk D: Consider therapy modification
Finerenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Finerenone. Risk X: Avoid combination
Flibanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Flibanserin. Management: Use of flibanserin with strong 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 combination
Flunitrazepam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Flunitrazepam. Risk C: Monitor therapy
Fluticasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Nasal). Risk X: Avoid combination
Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Management: Consider alternatives to this combination if possible. Coadministration of fluticasone propionate and strong CYP3A4 inhibitors is not recommended. If combined, monitor patients for systemic corticosteroid adverse effects (eg, adrenal suppression). Risk D: Consider therapy modification
Fluticasone (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Topical). Risk C: Monitor therapy
Fosamprenavir: Itraconazole may increase serum concentrations of the active metabolite(s) of Fosamprenavir. Specifically, amprenavir concentrations may be increased. Fosamprenavir may increase the serum concentration of Itraconazole. Management: Limit the adult maximum itraconazole dose to 200 mg/day with fosamprenavir/ritonavir. In patients receiving fosamprenavir without ritonavir, patients receiving greater than 400 mg/day itraconazole may also require dose reduction. Risk D: Consider therapy modification
Fosaprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fosaprepitant. Risk X: Avoid combination
Fostamatinib: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fostamatinib. Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Futibatinib: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Futibatinib. Risk X: Avoid combination
Galantamine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Galantamine. Risk C: Monitor therapy
Gefitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Gefitinib. Risk C: Monitor therapy
Gepirone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Gepirone. Risk X: Avoid combination
Gilteritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Gilteritinib. Management: Consider alternatives to the use of a strong CYP3A4 inhibitor with gilteritinib. If the combination cannot be avoided, monitor more closely for evidence of gilteritinib toxicities. Risk D: Consider therapy modification
Glasdegib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Glasdegib. Management: Consider alternatives to this combination when possible. If the combination must be used, monitor closely for evidence of QT interval prolongation and other adverse reactions to glasdegib. Risk D: Consider therapy modification
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy
Grapefruit Juice: May decrease the serum concentration of Itraconazole. Grapefruit Juice may increase the serum concentration of Itraconazole. Risk C: Monitor therapy
GuanFACINE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of GuanFACINE. Management: Reduce the extended-release guanfacine dose 50% when combined with a strong CYP3A4 inhibitor. Monitor for increased guanfacine toxicities when these agents are combined. Risk D: Consider therapy modification
Halofantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Halofantrine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for halofantrine toxicities, including QTc interval prolongation. Risk D: Consider therapy modification
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Haloperidol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Haloperidol. Risk C: Monitor therapy
Histamine H2 Receptor Antagonists: May increase the serum concentration of Itraconazole. Histamine H2 Receptor Antagonists may decrease the serum concentration of Itraconazole. Management: Administer Sporanox brand itraconazole at least 2 hours before or 2 hours after administration of any histamine H2 receptor antagonists (H2RAs). Exposure to Tolsura brand itraconazole may be increased by H2RAs; consider itraconazole dose reduction. Risk D: Consider therapy modification
Hormonal Contraceptives: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Hormonal Contraceptives. Risk C: Monitor therapy
HYDROcodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of HYDROcodone. Risk C: Monitor therapy
Hydrocortisone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Hydrocortisone (Systemic). Risk C: Monitor therapy
Ibrexafungerp: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ibrexafungerp. Management: Decrease the ibrexafungerp dose to 150 mg every 12 hours for 2 doses in patients receiving strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Ibrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ibrutinib. Management: Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for 7 days or less), interrupt ibrutinib therapy until the strong CYP3A4 inhibitor is discontinued. Risk X: Avoid combination
Idelalisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Idelalisib. Management: Use alternative therapies that are not strong CYP3A4 inhibitors whenever possible. If unable to use alternative drugs, monitor patients more frequently for idelalisib toxicities. Risk D: Consider therapy modification
Ifosfamide: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Risk C: Monitor therapy
Iloperidone: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolites P88 and P95 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Imatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imatinib. Risk C: Monitor therapy
Imidafenacin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imidafenacin. Risk C: Monitor therapy
Indinavir: Itraconazole may increase the serum concentration of Indinavir. Indinavir may increase the serum concentration of Itraconazole. Management: Reduce the indinavir dose to 600 mg every 8 hours when given with itraconazole. Monitor for increased systemic effects (including adverse/toxic effects) of itraconazole. Risk D: Consider therapy modification
Infigratinib: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Infigratinib. Risk X: Avoid combination
Inhibitors of the Proton Pump (PPIs and PCABs): May increase the serum concentration of Itraconazole. This specifically applies to the super bioavailable itraconazole products (eg, Tolsura brand). Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Itraconazole. This specifically applies to the non-super bioavailable itraconazole products (eg, Sporanox brand and its generics). Management: Exposure to Tolsura brand itraconazole may be increased by PPIs or PCABs ; consider itraconazole dose reduction. Exposure to Sporanox brand itraconazole may be decreased. Give Sporanox brand itraconazole at least 2 hrs before or 2 hrs after PPIs or PCABs. Risk D: Consider therapy modification
Irinotecan Products: Itraconazole may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. Risk X: Avoid combination
Isavuconazonium Sulfate: Itraconazole may increase the serum concentration of Isavuconazonium Sulfate. Risk X: Avoid combination
Isoniazid: May decrease the serum concentration of Itraconazole. Risk X: Avoid combination
Isradipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Isradipine. Risk C: Monitor therapy
Istradefylline: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Istradefylline. Management: Limit the maximum istradefylline dose to 20 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased istradefylline effects/toxicities. Risk D: Consider therapy modification
Ivabradine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivabradine. Risk X: Avoid combination
Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult full drug interaction monograph content for age- and weight-specific recommendations. Risk D: Consider therapy modification
Ivosidenib: Itraconazole may increase the serum concentration of Ivosidenib. Ivosidenib may decrease the serum concentration of Itraconazole. Risk X: Avoid combination
Ixabepilone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone. Management: Avoid use of ixabepilone and strong CYP3A4 inhibitors when possible. If combined, reduce the ixabepilone dose to 20 mg/m2. The previous ixabepilone dose can be resumed 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Ketamine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ketamine. Risk C: Monitor therapy
Ketoconazole (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ketoconazole (Systemic). Risk C: Monitor therapy
Lacidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lacidipine. Risk C: Monitor therapy
Lapatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lapatinib. Management: Avoid use of lapatinib and strong CYP3A4 inhibitors when possible. If combined, a reduced lapatinib dose of 500 mg daily should be considered. The previous lapatinib dose can be resumed 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Larotrectinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Larotrectinib. Management: Avoid use of strong CYP3A4 inhibitors with larotrectinib. If this combination cannot be avoided, reduce the larotrectinib dose by 50%. Increase to previous dose after stopping the inhibitor after a period of 3 to 5 times the inhibitor's half-life. Risk D: Consider therapy modification
Lefamulin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets and strong inhibitors of CYP3A4. Risk X: Avoid combination
Lemborexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lemborexant. Risk X: Avoid combination
Leniolisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Leniolisib. Risk X: Avoid combination
Lercanidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lercanidipine. Risk X: Avoid combination
Letermovir: Itraconazole may increase the serum concentration of Letermovir. Letermovir may decrease the serum concentration of Itraconazole. Risk C: Monitor therapy
Leuprolide and Norethindrone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Leuprolide and Norethindrone. Specifically, concentrations of norethindrone may increase. Risk C: Monitor therapy
Levamlodipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levamlodipine. Risk C: Monitor therapy
Levobupivacaine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine. Risk C: Monitor therapy
Levoketoconazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levoketoconazole. Risk X: Avoid combination
Levomethadone: Itraconazole may increase the serum concentration of Levomethadone. Risk C: Monitor therapy
Levomilnacipran: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levomilnacipran. Management: The dose of levomilnacipran should not exceed 80 mg once daily when used with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Lidocaine (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy
Lomitapide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lomitapide. Risk X: Avoid combination
Lonafarnib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lonafarnib. Risk X: Avoid combination
Lopinavir: May increase the serum concentration of Itraconazole. Management: Itraconazole doses greater than 200 mg/day are not recommended in combination with lopinavir/ritonavir. Risk D: Consider therapy modification
Lorlatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with strong CYP3A4 inhibitors. If the combination cannot be avoided, reduce the lorlatinib dose from 100 mg once daily to 75 mg once daily, or from 75 mg once daily to 50 mg once daily. Risk D: Consider therapy modification
Lovastatin: Itraconazole may increase the serum concentration of Lovastatin. Risk X: Avoid combination
Lumateperone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumateperone. Management: Limit the lumateperone dose to 10.5 mg once daily when used with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Lurasidone: Itraconazole may increase the serum concentration of Lurasidone. Risk X: Avoid combination
Lurbinectedin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and strong CYP3A4 inhibitors. If coadministration with a strong CYP3A4 inhibitor cannot be avoided, reduce the lurbinectedin dose by 50%. Risk D: Consider therapy modification
Macitentan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Macitentan. Risk X: Avoid combination
Manidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Manidipine. Management: Consider avoiding concomitant use of manidipine and strong CYP3A4 inhibitors. If combined, monitor closely for increased manidipine effects and toxicities. Manidipine dose reductions may be required. Risk D: Consider therapy modification
Maraviroc: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. Management: Reduce maraviroc to 150mg twice/day in adult and pediatrics weighing 40kg or more. See full interaction monograph for dose adjustments in pediatrics weighing 10 to less than 40kg. Do not use if CrCl less than 30mL/min or in those weighing less than 10 kg. Risk D: Consider therapy modification
Mavacamten: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mavacamten. Risk X: Avoid combination
Mefloquine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mefloquine. Risk C: Monitor therapy
Meloxicam: Itraconazole may decrease the serum concentration of Meloxicam. Risk C: Monitor therapy
Meperidine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Meperidine. Risk C: Monitor therapy
Methadone: Itraconazole may enhance the QTc-prolonging effect of Methadone. Itraconazole may increase the serum concentration of Methadone. Risk X: Avoid combination
MethylPREDNISolone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MethylPREDNISolone. Risk C: Monitor therapy
Midazolam: Itraconazole may increase the serum concentration of Midazolam. Management: Oral midazolam is contraindicated with, and for 2 weeks after, itraconazole. Avoid use with nasal midazolam. Consider alternatives to use with other routes of midazolam (IV, IM) when possible. Consider use of lower midazolam doses if combined. Risk X: Avoid combination
Midostaurin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Midostaurin. Management: Seek alternatives to the concomitant use of midostaurin and strong CYP3A4 inhibitors if possible. If concomitant use cannot be avoided, monitor patients for increased risk of adverse reactions. Risk D: Consider therapy modification
MiFEPRIStone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MiFEPRIStone. Management: For treatment of hyperglycemia in Cushing's syndrome, start mifepristone at 300 mg/day, may titrate to a maximum of 900 mg/day. If starting a strong CYP3A4 inhibitor and taking > 300 mg/day mifepristone, decrease the mifepristone dose by 300 mg/day. Risk D: Consider therapy modification
Mirodenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mirodenafil. Management: Consider using a lower dose of mirodenafil when used with strong CYP3A4 inhibitors. Monitor for increased mirodenafil effects/toxicities with the use of this combination. Risk D: Consider therapy modification
Mirtazapine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mirtazapine. Risk C: Monitor therapy
Mirvetuximab Soravtansine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mirvetuximab Soravtansine. Risk C: Monitor therapy
Mitapivat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mitapivat. Risk X: Avoid combination
Mizolastine: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Mizolastine. Risk X: Avoid combination
Mobocertinib: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Mobocertinib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mobocertinib. Risk X: Avoid combination
Mometasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mometasone (Nasal). Risk C: Monitor therapy
Mometasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mometasone (Oral Inhalation). Risk C: Monitor therapy
Mometasone (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mometasone (Topical). Risk C: Monitor therapy
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Risk C: Monitor therapy
Naldemedine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naldemedine. Risk C: Monitor therapy
Nalfurafine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nalfurafine. Risk C: Monitor therapy
Naloxegol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naloxegol. Risk X: Avoid combination
Nelfinavir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nelfinavir. Risk C: Monitor therapy
Neratinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Neratinib. Risk X: Avoid combination
Nevirapine: May decrease the serum concentration of Itraconazole. Risk X: Avoid combination
NiCARdipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NiCARdipine. Risk C: Monitor therapy
NIFEdipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NIFEdipine. Management: Consider alternatives to this combination when possible. If combined, initiate nifedipine at the lowest dose available and monitor patients closely for increased nifedipine effects and toxicities (eg, hypotension, edema). Risk D: Consider therapy modification
Nilotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib. Management: Avoid if possible. If combination needed, decrease nilotinib to 300 mg once/day for patients with resistant or intolerant Ph+ CML or to 200 mg once/day for patients with newly diagnosed Ph+ CML in chronic phase. Risk D: Consider therapy modification
Nilvadipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilvadipine. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NiMODipine. Risk X: Avoid combination
Nintedanib: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Nintedanib. Risk C: Monitor therapy
Nirmatrelvir and Ritonavir: Itraconazole may increase the serum concentration of Nirmatrelvir and Ritonavir. Nirmatrelvir and Ritonavir may increase the serum concentration of Itraconazole. Management: Limit the adult maximum itraconazole dose to 200 mg/day in patients receiving nirmatrelvir/ritonavir. Risk D: Consider therapy modification
Nirogacestat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nirogacestat. Risk X: Avoid combination
Nisoldipine: Itraconazole may increase the serum concentration of Nisoldipine. Risk X: Avoid combination
Nitrendipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nitrendipine. Risk C: Monitor therapy
Olaparib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Olaparib. Management: Avoid use of strong CYP3A4 inhibitors with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib tablets should be reduced to 100 mg twice daily and the dose of olaparib capsules should be reduced to 150 mg twice daily. Risk D: Consider therapy modification
Oliceridine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Oliceridine. Risk C: Monitor therapy
Olmutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Olmutinib. Risk C: Monitor therapy
Omaveloxolone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Omaveloxolone. Management: Avoid this combination if possible. If coadministration is required, decrease the omaveloxolone dose to 50 mg daily and monitor closely for adverse reactions. Discontinue coadministration if adverse reactions occur. Risk D: Consider therapy modification
Orelabrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Orelabrutinib. Risk X: Avoid combination
Osilodrostat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Osilodrostat. Management: Reduce osilodrostat dose by 50% during coadministration with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Ospemifene: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ospemifene. Risk C: Monitor therapy
OxyBUTYnin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of OxyBUTYnin. Risk C: Monitor therapy
OxyCODONE: CYP3A4 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 therapy
PACLitaxel (Conventional): CYP3A4 Inhibitors (Strong) may increase the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
PACLitaxel (Protein Bound): CYP3A4 Inhibitors (Strong) may increase the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy
Pacritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pacritinib. Risk X: Avoid combination
Palbociclib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Palbociclib. Management: Avoid concurrent use of strong CYP3A4 inhibitors with palbociclib when possible. If the use of a strong CYP3A4 inhibitor cannot be avoided, decrease the palbociclib dose to 75 mg/day. Risk D: Consider therapy modification
Palovarotene: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Palovarotene. Risk X: Avoid combination
Panobinostat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Panobinostat. Management: Reduce the panobinostat dose to 10 mg when it must be used with a strong CYP3A4 inhibitor. Monitor patient response to therapy closely for evidence of more severe adverse effects related to panobinostat therapy. Risk D: Consider therapy modification
Parecoxib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Parecoxib. Specifically, serum concentrations of the active moiety valdecoxib may be increased. Risk C: Monitor therapy
Paricalcitol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Paricalcitol. Risk C: Monitor therapy
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Pemigatinib: CYP3A4 Inhibitors (Strong) 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 strong inhibitor once 3 half-lives of the inhibitor has passed. Risk D: Consider therapy modification
Pexidartinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pexidartinib. Management: If combined use cannot be avoided, pexidartinib dose should be reduced. For the 125 mg capsules: reduce pexidartinib doses of 500 mg or 375 mg daily to 125 mg twice daily. Reduce pexidartinib 250 mg daily to 125 mg once daily. Risk D: Consider therapy modification
Pimavanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimavanserin. Management: Decrease the pimavanserin dose to 10 mg daily when combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Pimecrolimus: CYP3A4 Inhibitors (Strong) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy
Pimozide: Itraconazole may increase the serum concentration of Pimozide. Risk X: Avoid combination
Piperaquine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Piperaquine. Risk C: Monitor therapy
Pirtobrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pirtobrutinib. Management: Avoid concomitant use when possible. If combined, reduce the pirtobrutinib dose by 50 mg. If current dose is 50 mg, interrupt pirtobrutinib treatment during strong CYP3A4 inhibitor use. Risk D: Consider therapy modification
Polatuzumab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be increased. Risk C: Monitor therapy
PONATinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of PONATinib. Management: Avoid concomitant use if possible. If combined, reduce ponatinib dose as follows: If taking 45 mg, reduce to 30 mg; if taking 30 mg, reduce to 15 mg; if taking 15 mg, reduce to 10 mg. If taking 10 mg, avoid concomitant use with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Pralsetinib: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Pralsetinib. Management: Avoid concomitant use if possible. If combined, reduce the pralsetinib dose. If taking 400 mg or 300 mg once daily, reduce to 200 mg once daily. If taking 200 mg once daily, reduce to 100 mg once daily. Risk D: Consider therapy modification
Pravastatin: Itraconazole may increase the serum concentration of Pravastatin. Risk C: Monitor therapy
Prazepam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Prazepam. Risk C: Monitor therapy
Praziquantel: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Praziquantel. Risk C: Monitor therapy
PrednisoLONE (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of PrednisoLONE (Systemic). Risk C: Monitor therapy
PredniSONE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of PredniSONE. Risk C: Monitor therapy
Propafenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Propafenone. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest 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 therapy
QUEtiapine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of QUEtiapine. Management: In quetiapine treated patients, reduce quetiapine to one-sixth of original dose after starting a strong CYP3A4 inhibitor. In those on strong CYP3A4 inhibitors, start quetiapine at lowest dose and up-titrate as needed. Risk D: Consider therapy modification
QuiNIDine: Itraconazole may increase the serum concentration of QuiNIDine. Risk X: Avoid combination
Quinidine (Non-Therapeutic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Quinidine (Non-Therapeutic). Risk C: Monitor therapy
QuiNINE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of QuiNINE. Risk C: Monitor therapy
Quizartinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Quizartinib. Management: If combination is necessary, reduce quizartinib dose as follows: from 53 mg daily to 26.5 mg daily; from 35.4 mg daily to 17.7 mg daily; from 26.5 mg daily to 17.7 mg daily. If taking 17.7 mg daily avoid quizartinib while on the strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Radotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Radotinib. Risk X: Avoid combination
Ramelteon: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ramelteon. Risk C: Monitor therapy
Ranolazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. Risk X: Avoid combination
Reboxetine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Reboxetine. Risk C: Monitor therapy
Red Yeast Rice: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin and related compounds found in Red Yeast Rice may be increased. Risk X: Avoid combination
Regorafenib: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Regorafenib. Risk X: Avoid combination
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider therapy modification
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider therapy modification
Repaglinide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Repotrectinib. Risk X: Avoid combination
Retapamulin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Retapamulin. Management: The use of retapamulin with strong CYP3A4 inhibitors is not recommended in patients less than 2 years old. No action is required in other populations. Risk C: Monitor therapy
Ribociclib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ribociclib. Management: Avoid use of ribociclib with strong CYP3A4 inhibitors when possible; if combined use cannot be avoided, reduce ribociclib dose to 400 mg once daily. Risk D: Consider therapy modification
Rifabutin: Itraconazole may increase the serum concentration of Rifabutin. Rifabutin may decrease the serum concentration of Itraconazole. Risk X: Avoid combination
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy
Rilpivirine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rilpivirine. Risk C: Monitor therapy
Rimegepant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rimegepant. Risk X: Avoid combination
Riociguat: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Riociguat. Management: Consider a riociguat starting dose of 0.5 mg 3 times a day when initiating riociguat in patients receiving strong CYP3A4 and P-gp inhibitors. Monitor for hypotension when these agents are combined and reduce the riociguat dose as needed. Risk D: Consider therapy modification
Ripretinib: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ripretinib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ripretinib. Risk C: Monitor therapy
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy
Ritonavir: May increase the serum concentration of Itraconazole. Management: Limit the adult maximum itraconazole dose to 200 mg/day in patients receiving ritonavir. Risk D: Consider therapy modification
Rivaroxaban: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Rivaroxaban. Risk X: Avoid combination
Roflumilast-Containing Products: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy
RomiDEPsin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy
Rosuvastatin: Itraconazole may increase the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Rupatadine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rupatadine. Risk X: Avoid combination
Ruxolitinib (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib (Systemic). Management: This combination should be avoided under some circumstances; dose adjustments may be required in some circumstances and depend on the indication for ruxolitinib. See monograph for details. Risk D: Consider therapy modification
Ruxolitinib (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib (Topical). Risk X: Avoid combination
Saccharomyces boulardii: Antifungal Agents (Systemic and Oral [Non-Absorbable]) may diminish the therapeutic effect of Saccharomyces boulardii. Risk X: Avoid combination
Salmeterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol. Risk X: Avoid combination
Saquinavir: Itraconazole may increase the serum concentration of Saquinavir. Saquinavir may increase the serum concentration of Itraconazole. Management: Limit the adult maximum itraconazole dose to 200 mg/day in patients receiving saquinavir/ritonavir and monitor for saquinavir adverse effects, including cardiac arrhythmias. Risk D: Consider therapy modification
SAXagliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SAXagliptin. Management: Limit the saxagliptin dose to 2.5 mg daily when combined with strong CYP3A4 inhibitors. When using the saxagliptin combination products saxagliptin/dapagliflozin or saxagliptin/dapagliflozin/metformin, avoid use with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Selpercatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Selpercatinib. Management: Avoid combination if possible. If use is necessary, reduce selpercatinib dose as follows: from 120 mg twice/day to 40 mg twice/day, or from 160 mg twice/day to 80 mg twice/day. Risk D: Consider therapy modification
Selumetinib: CYP3A4 Inhibitors (Strong) 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 modification
Sertindole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sertindole. Risk X: Avoid combination
Sibutramine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Sibutramine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sibutramine. Risk C: Monitor therapy
Sildenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sildenafil. Management: Use of sildenafil for pulmonary arterial hypertension (PAH) should be avoided with strong CYP3A4 inhibitors. When used for erectile dysfunction, consider using a lower starting dose of 25 mg and monitor patients for sildenafil toxicities. Risk D: Consider therapy modification
Silodosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin. Risk X: Avoid combination
Simeprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simeprevir. Risk X: Avoid combination
Simvastatin: Itraconazole may increase the serum concentration of Simvastatin. Risk X: Avoid combination
Sirolimus (Conventional): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with strong CYP3A4 inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Concomitant use of sirolimus and voriconazole or posaconazole is contraindicated. Risk D: Consider therapy modification
Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider therapy modification
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination
Sirolimus (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sirolimus (Topical). Risk C: Monitor therapy
Solifenacin: Itraconazole may increase the serum concentration of Solifenacin. Management: Limit adult solifenacin doses to 5 mg daily and limit pediatric doses to the starting dose. Do not use with itraconazole, or for 2 weeks after itraconazole discontinuation, in patients with moderate to severe hepatic impairment or severe renal impairment. Risk D: Consider therapy modification
Sonidegib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sonidegib. Risk X: Avoid combination
Sparsentan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sparsentan. Risk X: Avoid combination
SUFentanil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SUFentanil. Management: If a strong CYP3A4 inhibitor is initiated in a patient on sufentanil, consider a sufentanil dose reduction and monitor for increased sufentanil effects and toxicities (eg, respiratory depression). Risk D: Consider therapy modification
SUNItinib: Itraconazole may increase the serum concentration of SUNItinib. Management: Avoid when possible. If combined, decrease sunitinib dose to a minimum of 37.5 mg daily when treating GIST or RCC. Decrease sunitinib dose to a minimum of 25 mg daily when treating PNET. Monitor patients for both reduced efficacy and increased toxicities. Risk D: Consider therapy modification
Suvorexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Suvorexant. Risk X: Avoid combination
Tacrolimus (Systemic): Itraconazole may increase the serum concentration of Tacrolimus (Systemic). Management: Monitor tacrolimus concentrations closely during therapy with itraconazole; tacrolimus dose reductions will likely be required. The magnitude of this interaction may be greater in older patients or those with one or more CYP3A5*3 alleles. Risk D: Consider therapy modification
Tacrolimus (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tacrolimus (Topical). Risk C: Monitor therapy
Tadalafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tadalafil. Management: Avoid this combination in patients taking tadalafil for pulmonary arterial hypertension. In patients taking tadalafil for ED or BPH, max tadalafil dose is 2.5 mg if taking daily or 10 mg no more frequently than every 72 hours if used as needed. Risk D: Consider therapy modification
Talazoparib: Itraconazole may increase the serum concentration of Talazoparib. Management: In breast cancer, if concurrent use cannot be avoided, reduce talazoparib dose to 0.75 mg once daily. In prostate cancer, monitor patients for increased adverse events. Risk D: Consider therapy modification
Tamsulosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. Risk X: Avoid combination
Tasimelteon: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tasimelteon. Risk C: Monitor therapy
Tazemetostat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tazemetostat. Risk X: Avoid combination
Tegaserod (Withdrawn from US Market): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod (Withdrawn from US Market). Risk C: Monitor therapy
Temsirolimus: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Management: Avoid concomitant use of temsirolimus and strong CYP3A4 inhibitors. If coadministration is unavoidable, decrease temsirolimus dose to 12.5 mg per week. Resume previous temsirolimus dose 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Risk C: Monitor therapy
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Terfenadine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Terfenadine. Risk X: Avoid combination
Tetrahydrocannabinol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol. Risk C: Monitor therapy
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor therapy
Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tezacaftor and Ivacaftor. Management: If combined with strong CYP3A4 inhibitors, tezacaftor/ivacaftor should be administered in the morning, twice a week, approximately 3 to 4 days apart. Tezacaftor/ivacaftor dose depends on age and weight; see full Lexi-Interact monograph for details. Risk D: Consider therapy modification
Thiotepa: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Thiotepa. Management: Avoid coadministration of thiotepa and strong CYP3A4 inhibitors. If concomitant use cannot be avoided, monitor for thiotepa adverse effects and decreased efficacy. Risk D: Consider therapy modification
Ticagrelor: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor. Risk X: Avoid combination
Tipranavir: May increase the serum concentration of Itraconazole. Management: Adult itraconazole doses greater than 200 mg/day are not recommended in patients treated with tipranavir. Risk D: Consider therapy modification
Tisotumab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tisotumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor therapy
Tofacitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tofacitinib. Management: Tofacitinib dose reductions are recommended when combined with strong CYP3A4 inhibitors. Recommended dose adjustments vary by tofacitinib formulation and therapeutic indication. See full Lexi Interact monograph for details. Risk D: Consider therapy modification
Tolterodine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolterodine. Management: The maximum recommended dose of tolterodine is 2 mg per day (1 mg twice daily for immediate-release tablets or 2 mg daily for extended-release capsules) when used together with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Tolvaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan. Risk X: Avoid combination
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Toremifene: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene. Management: Use of toremifene with strong CYP3A4 inhibitors should be avoided if possible. If coadministration is necessary, monitor for increased toremifene toxicities, including QTc interval prolongation. Risk D: Consider therapy modification
Trabectedin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Trabectedin. Risk X: Avoid combination
TraMADol: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of TraMADol. CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraMADol. Risk C: Monitor therapy
TraZODone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraZODone. Management: Consider the use of a lower trazodone dose and monitor for increased trazodone effects (eg, sedation, QTc prolongation) if combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Tretinoin (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tretinoin (Systemic). Risk C: Monitor therapy
Triamcinolone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triamcinolone (Nasal). Risk C: Monitor therapy
Triamcinolone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triamcinolone (Ophthalmic). Risk C: Monitor therapy
Triamcinolone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triamcinolone (Systemic). Management: Consider alternatives to this combination when possible. If combined, monitor for increased corticosteroid adverse effects during coadministration of triamcinolone and strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Triamcinolone (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triamcinolone (Topical). Risk C: Monitor therapy
Triazolam: Itraconazole may increase the serum concentration of Triazolam. Risk X: Avoid combination
Ubrogepant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ubrogepant. Risk X: Avoid combination
Udenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Udenafil. Risk X: Avoid combination
Ulipristal: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ulipristal. Risk C: Monitor therapy
Upadacitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Upadacitinib. Management: Upadacitinib dose adjustments are needed when combined with strong CYP3A4 inhibitors. Specific adjustments vary based on upadacitinib indication. See full interact monograph for details. Risk D: Consider therapy modification
Valbenazine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Valbenazine. Management: Reduce the valbenazine dose to 40 mg daily when combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Vamorolone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vamorolone. Management: Reduce the vamorolone dose to 4 mg/kg daily, with a maximum dose of 200 mg daily for patients weighing over 50 kg, when combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Vardenafil: Itraconazole may increase the serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to 5 mg per 24 hours with itraconazole 200 mg/day and 2.5 mg per 24 hours with itraconazole 400 mg/day. Avoid concomitant use of Staxyn (vardenafil) and itraconazole. Combined use is contraindicated outside of the US. Risk D: Consider therapy modification
Vemurafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vemurafenib. Management: Avoid concurrent use of vemurafenib with strong CYP3A4 inhibitors when possible. If concomitant use is unavoidable, consider a vemurafenib dose reduction if clinically indicated. Risk D: Consider therapy modification
Venetoclax: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Venetoclax. Management: Coadministration is contraindicated during venetoclax initiation and ramp-up in CLL/SLL patients. Reduced venetoclax doses are required during ramp-up for patients with AML, and all maintenance therapy. See full Lexi Interact monograph for details. Risk D: Consider therapy modification
Verapamil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Verapamil. Risk C: Monitor therapy
Vilanterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilanterol. Risk C: Monitor therapy
Vilazodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. Management: Limit the maximum vilazodone dose to 20 mg daily in patients receiving strong CYP3A4 inhibitors. The original vilazodone dose can be resumed following discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification
VinBLAStine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinBLAStine. Risk C: Monitor therapy
VinCRIStine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinCRIStine. Management: Seek alternatives to this combination when possible. If combined, monitor closely for vincristine toxicities (eg, neurotoxicity, gastrointestinal toxicity, myelosuppression). Risk D: Consider therapy modification
VinCRIStine (Liposomal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination
Vindesine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vindesine. Risk C: Monitor therapy
Vinflunine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Vinflunine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinflunine. Risk X: Avoid combination
Vinorelbine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinorelbine. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Itraconazole may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
Voclosporin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Voclosporin. Risk X: Avoid combination
Vorapaxar: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vorapaxar. Risk X: Avoid combination
Voriconazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Voriconazole. Risk C: Monitor therapy
Zanubrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg once daily during coadministration with a strong CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details. Risk D: Consider therapy modification
Ziprasidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ziprasidone. Risk C: Monitor therapy
Zolpidem: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zolpidem. Risk C: Monitor therapy
Zopiclone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zopiclone. Management: If coadministered with strong CYP3A4 inhibitors, initiate zopiclone at 3.75 mg in adults, with a maximum dose of 5 mg. Monitor for zopiclone toxicity (eg, drowsiness, confusion, lethargy, ataxia, respiratory depression). Risk D: Consider therapy modification
Zuranolone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zuranolone. Management: Reduce the zuranolone dose to 30 mg once daily when used concomitantly with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Capsule (100 mg [Sporanox]): Absorption enhanced by food and possibly by gastric acidity. Non-diet cola drinks have been shown to increase the absorption of the capsules in patients with achlorhydria or those taking H2-receptor antagonists or other gastric acid suppressors. Grapefruit/grapefruit juice may decrease or increase itraconazole serum levels. Management: Take 100 mg capsules (Sporanox) immediately after meals. Keep grapefruit/grapefruit juice consumption consistent; monitor for altered effects with concomitant use.
Capsule (65 mg [Tolsura]): Absorption increased when administered on an empty stomach; however, administration of Tolsura (2 x 65 mg capsule) with food results in exposure similar to those achieved when Sporanox (2 x 100 mg capsule) is administered with food. Management: Take 65 mg capsules (Tolsura) with food.
Oral solution: Food decreases the bioavailability and increases the time to peak concentration. Management: Take solution on an empty stomach 1 hour before or 2 hours after meals.
Use is contraindicated for the treatment of onychomycosis in patients planning to become pregnant. Due to the potential risk of congenital malformations, the manufacturer recommends that when used for the treatment of onychomycosis, patients who may become pregnant should use highly effective contraception during treatment and for 2 months following treatment. Therapy should begin on the second or third day following menses.
Based on available data, an increased risk of adverse pregnancy outcomes (major congenital malformations, or spontaneous abortion/stillbirth) has not been associated with maternal use of itraconazole in short courses; however, the risk of specific birth defects has not been adequately studied (Liu 2020). Congenital abnormalities (eg, skeletal, genitourinary tract, cardiovascular, and ophthalmic malformations; chromosomal abnormalities; multiple other malformations) have been reported during postmarketing surveillance; however, a causal relationship has not been established.
In general, all azole antifungals should be avoided in the first trimester. Itraconazole is specifically contraindicated for the treatment of onychomycosis during pregnancy. Although itraconazole is approved for the treatment of various fungal infections, when treatment of a systemic fungal infection is needed in pregnant patients, itraconazole should be avoided, especially during the first trimester in order to decrease the risk of potential teratogenic exposure (HHS [OI adult 2020]; IDSA [Chapman 2008]; IDSA [Galgiani 2016]; IDSA [Pappas 2016]; IDSA [Wheat 2007]).
Itraconazole is present in breast milk.
According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Capsule (100 mg [Sporanox] and 65 mg [Tolsura]): Take with food.
Solution: Take without food, if possible.
Liver function in patients with preexisting hepatic dysfunction, and in all patients as clinically indicated; renal function; signs/symptoms of heart failure; signs and symptoms of neuropathy.
For invasive aspergillosis (treatment or prolonged prophylaxis), guidelines recommend monitoring serum trough concentrations (IDSA [Patterson 2016]). Consider monitoring serum trough concentrations for other infections; itraconazole has a variable pharmacokinetic profile and high concentrations may increase the risk of adverse events (Lestner 2009; MSG-ERC [Johnson 2020]).
Invasive aspergillosis:
Timing of concentrations: Obtain trough after steady state has been reached (4 to 7 days after therapy initiation); the need for continued or repeat monitoring is a patient specific decision influenced by many factors (eg, infection severity, cost, assay availability) (IDSA [Patterson 2016]).
Recommended range: Most experts recommend dosing to achieve trough concentrations >0.5 to 1 mcg/mL. Limited data suggest trough concentrations >3 mcg/mL may be associated with increased toxicity (IDSA [Patterson 2016]).
Interferes with cytochrome P450 activity, decreasing ergosterol synthesis (principal sterol in fungal cell membrane) and inhibiting cell membrane formation
Absorption:
Capsule: The 100 mg capsule (Sporanox) requires gastric acidity (absorption is increased when administered with food). The 65 mg capsule (Tolsura) has increased absorption when administered on an empty stomach; however, administration of Tolsura (2 x 65 mg capsule) with food results in exposures similar to those achieved when Sporanox (2 x 100 mg capsule) is administered with food.
Oral solution: Absorption increased on empty stomach.
Distribution: Highly lipophilic and tissue concentrations are higher than plasma concentrations. The highest concentrations: adipose, omentum, endometrium, cervical and vaginal mucus, and skin/nails. Aqueous fluids (eg, CSF and urine) contain negligible amounts; distributes into bronchial exudate and sputum.
Infants ≥7 months, Children, and Adolescents <18 years: Vd: Single dose: 18.5 ± 14.2 L/kg (Abdel-Rahman 2007).
Adults: Vd: >700 L.
Protein binding, plasma: 99.8%; metabolite hydroxy-itraconazole: 99.6%.
Metabolism: Extensively hepatic via CYP3A4 into >30 metabolites including hydroxy-itraconazole (major metabolite); appears to have in vitro antifungal activity. Main metabolic pathway is oxidation; may undergo saturation metabolism with multiple dosing.
Bioavailability: Variable; Oral solution: ~55%; increases by 30% under fasted conditions (oral solution); Note: Oral solution has a higher degree of bioavailability (149% ± 68%) relative to oral capsules; should not be interchanged.
Half-life elimination:
Infants ≥6 months and Children <2 years: Oral solution: Itraconazole: 47.4 ± 55 hours; hydroxyitraconazole: 18 ± 18.1 hours (de Repentigny 1998).
Children 2 to <5 years: Oral solution: Itraconazole: 30.6 ± 25.3 hours; hydroxyitraconazole: 17.1 ± 14.5 hours (de Repentigny 1998).
Children ≥5 years: Oral solution: Itraconazole: 28.3 ± 9.6 hours; hydroxyitraconazole: 17.9 ± 8.7 hours (de Repentigny 1998).
Adults: Oral: Single dose: 16 to 28 hours, Multiple doses: 34 to 42 hours; Cirrhosis (single dose): 37 hours (range: 20 to 54 hours).
Time to peak, plasma: Capsules: 2 to 5 hours; Oral solution: 2.5 hours.
Excretion: Urine (<1% active drug, 35% as inactive metabolites); feces (54%; ~3% to 18% as unchanged drug).
Altered kidney function: Bioavailability is slightly reduced.
Hepatic function impairment: Cmax was reduced by 47% and resulted in a twofold increase in half-life (capsules).
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