(i tra KOE na zole)
Aspergillosis (capsules): Treatment of pulmonary and extrapulmonary aspergillosis in immunocompromised and nonimmunocompromised patients who are intolerant of or refractory to amphotericin B therapy.
Blastomycosis (capsules): Treatment of pulmonary and extrapulmonary blastomycosis in immunocompromised and nonimmunocompromised patients.
Histoplasmosis (capsules): Treatment of histoplasmosis, including chronic cavitary pulmonary disease and disseminated, nonmeningeal histoplasmosis in immunocompromised and nonimmunocompromised patients.
Onychomycosis:
Capsules: Treatment of onychomycosis of the toenail, with or without fingernail involvement, and onychomycosis of the fingernail caused by dermatophytes (tinea unguium) in nonimmunocompromised patients
Tablets: Treatment of onychomycosis of the toenail caused by Trichophyton rubrum or Trichophyton mentagrophytes in nonimmunocompromised patients
Oropharyngeal/Esophageal candidiasis (oral solution): Treatment of oropharyngeal and esophageal candidiasis
Canadian labeling: Oral capsules: Additional indications (not in US labeling):
Candidiasis, oral and/or esophageal: Treatment of oral and/or esophageal candidiasis in immunocompromised and immunocompetent patients
Chromomycosis: Treatment of chromomycosis in immunocompromised and immunocompetent patients
Dermatomycoses: Treatment of dermatomycoses due to tinea pedis, tinea cruris, tinea corporis, and of pityriasis versicolor in patients for whom oral therapy is appropriate
Onychomycosis: Treatment of onychomycosis in immunocompromised and immunocompetent patients
Paracoccidioidomycosis: Treatment of paracoccidioidomycosis in immunocompromised and immunocompetent patients
Sporotrichosis: Treatment of cutaneous and lymphatic sporotrichosis in immunocompromised and immunocompetent patients
Hypersensitivity to itraconazole or any component of the formulation; concurrent administration with cisapride, disopyramide, dofetilide, dronedarone, eplerenone, ergot derivatives, felodipine, irinotecan, lovastatin, lurasidone, methadone, midazolam (oral), nisoldipine, pimozide, quinidine, ranolazine, simvastatin, ticagrelor, or triazolam; concurrent administration with colchicine, fesoterodine, telithromycin, and solifenacin in patients with varying degrees of renal or hepatic impairment; 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 intend to become pregnant
Canadian labeling: Additional contraindications (not in US labeling): Concurrent administration with domperidone, eletriptan, fesoterodine in patients with moderate to severe renal or hepatic impairment, or solifenacin in patients with severe renal impairment or moderate to severe hepatic impairment (capsule, oral solution); Concurrent administration with the following drugs (none of which are available in Canada): Astemizole, bepridil, halofantrine, ivabradine, lercanidipine, levacetylmethadol, mizolastine, telithromycin (in patients with severe renal or hepatic impairment), sertindole, terfenadine (capsule, oral solution); treatment of dermatomycosis (tinea pedis, tinea cruris, tinea corporis, pityriasis versicolor) in women who are pregnant or intend to become pregnant (capsule)
Do not administer itraconazole for the treatment of onychomycosis in patients with evidence of ventricular dysfunction, such as congestive heart failure (CHF) or a history of CHF. If signs or symptoms of CHF occur during administration of itraconazole oral solution, reassess continued itraconazole use. If signs or symptoms of CHF occur during administration of itraconazole capsules or tablets, discontinue administration. When itraconazole was administered intravenously (IV) to dogs and healthy human volunteers, negative inotropic effects were seen.
Drug interactions:Coadministration of the following drugs is contraindicated with itraconazole: methadone, disopyramide, dofetilide, dronedarone, quinidine, ergot alkaloids (eg, dihydroergotamine, ergometrine [ergonovine], ergotamine, methylergometrine [methylergonovine]), irinotecan, lurasidone, oral midazolam, pimozide, triazolam, felodipine, nisoldipine, ranolazine, eplerenone, cisapride, lovastatin, simvastatin, ticagrelor and, in subjects with varying degrees of renal or hepatic impairment, colchicine, fesoterodine, telithromycin, and solifenacin. 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.
Aspergillosis: Oral capsule: 200 to 400 mg daily. Note: For life-threatening infections, the US labeling recommends administering a loading dose of 200 mg 3 times daily (total: 600 mg daily) for the first 3 days of therapy. Continue treatment for at least 3 months and until clinical and laboratory evidence suggest that infection has resolved.
Aspergillosis, invasive (salvage therapy; voriconazole-susceptible): Duration of therapy should be a minimum of 6 to 12 weeks or throughout period of immunosuppression: Oral capsule: 200 to 400 mg daily; Note: 2008 IDSA guidelines recommend 600 mg/day for 3 days, followed by 400 mg daily (Walsh, 2008).
Aspergillosis, allergic (ABPA, sinusitis): Oral: 200 mg daily; may be used in conjunction with corticosteroids (Andes, 2000; Walsh, 2008)
Blastomycosis:Manufacturer labeling: Oral capsule: Initial: 200 mg once daily; if no clinical improvement or evidence of progressive infection, may increase dose in increments of 100 mg up to maximum of 400 mg daily. Doses >200 mg daily should be administered in 2 divided doses. Note: For life-threatening infections, the US labeling recommends administering a loading dose of 200 mg 3 times daily (total: 600 mg daily) for the first 3 days of therapy. Continue treatment for at least 3 months and until clinical and laboratory evidence suggest that infection has resolved.
Alternative dosing: 200 mg 3 times daily for 3 days, then 200 mg twice daily for 6 to 12 months; in moderately severe to severe infection, therapy should be initiated with ~2 weeks of amphotericin B (Chapman, 2008).
Candidiasis: Oral:
Esophageal:
US labeling: Oral solution: 100 to 200 mg once daily for a minimum of 3 weeks; continue dosing for 2 weeks after resolution of symptoms
Alternate dosing: Oral solution: Fluconazole-refractory disease: 200 mg once daily for 14 to 21 days (IDSA [Pappas 2016])
Canadian labeling:
Oral solution: 100 to 200 mg once daily for a minimum of 3 weeks; continue dosing for 2 weeks after resolution of symptoms
Oral capsules: 100 mg once daily for 4 weeks; increase dose to 200 mg once daily in patients with AIDS and neutropenic patients
Alternate dosing: HIV-infected patients: Oral solution: 200 mg once daily for 14 to 21 days (HHS [OI adult 2015])
Oropharyngeal:
US labeling: Oral solution: 200 mg once daily for 1 to 2 weeks; in patients unresponsive or refractory to fluconazole: 100 mg twice daily (clinical response expected in 2 to 4 weeks)
Alternate dosing: Oral solution: Fluconazole-refractory disease: 200 mg once daily for up to 28 days (IDSA [Pappas 2016])
Canadian labeling:
Oral solution: 200 mg once daily or in divided doses daily for 1 to 2 weeks
Oral capsules: 100 mg once daily for 2 weeks; increase dose to 200 mg once daily in patients with AIDS and neutropenic patients
Alternate dosing: HIV-infected patients (alternative to preferred therapy): Oral solution: 200 mg once daily for 7 to 14 days (HHS [OI adult 2015])
Vulvo-vaginal (uncomplicated) in HIV-infected patients (alternative to preferred therapy) (off-label use): Oral solution: 200 mg once daily for 3 to 7 days (HHS [OI adult 2015])
Chromomycosis: Canadian labeling (not in US labeling): Oral: 200 mg once daily for 6 months (when due to Fonsecaea pedrosoi) or 100 mg once daily for 3 months (when due to Cladosporium carrioni)
Coccidioidomycosis (nonprogressive, nondisseminated disease): 200 mg twice daily or 3 times daily (Galgiani 2005)
Coccidioidal pneumonia: Oral:
Mild to moderate: 200 mg twice daily (Galgiani 2005)
HIV-infected patients (focal pneumonia): 200 mg twice daily (HHS [OI adult 2015])
Coccidioidal meningitis: Oral: 400 to 600 mg daily (Galgiani 2005)
Coccidioidal meningitis in HIV-infected patients (off-label use; HHS [OI adult 2015]) (alternative to preferred therapy): Oral:
Treatment: 200 mg 3 times daily for 3 days, then 200 mg twice daily, followed by chronic suppressive therapy
Chronic suppressive therapy: 200 mg twice daily continued indefinitely, even with increase in CD4 count on ART
Histoplasmosis:
Treatment:
Manufacturers labeling: Oral capsule: Initial: 200 mg once daily; if no clinical improvement or evidence of progressive infection, may increase dose in increments of 100 mg up to maximum of 400 mg daily. Doses >200 mg daily should be administered in 2 divided doses. Note: For life-threatening infections, the US labeling recommends administering a loading dose of 200 mg 3 times daily (total: 600 mg daily) for the first 3 days of therapy. Continue treatment for at least 3 months and until clinical and laboratory evidence suggest that infection has resolved.
Alternate dosing: 200 mg 3 times daily for 3 days, then 200 mg twice daily (or once daily in mild-moderate disease) for 6 to 12 weeks in mild-moderate disease or ≥12 months in progressive disseminated or chronic cavitary pulmonary histoplasmosis; in moderately-severe to severe infection, therapy should be initiated with ~2 weeks of a lipid formation of amphotericin B (Wheat, 2007). Duration of twice daily maintenance therapy should be at least 12 months in HIV-infected patients (HHS [OI adult 2015])
Prophylaxis (off-label use):
Primary prophylaxis in HIV-infected patients: 200 mg once daily; primary prophylaxis is indicated when CD4 count <150 cells/mm3 and at increased risk of exposure (HHS [OI adult 2015])
Long-term suppression therapy (secondary prophylaxis) in HIV-infected patients: 200 mg once daily; long-term suppressive therapy is indicated in patients who relapse despite appropriate therapy or in patients with CNS or severe disseminated infection (HHS [OI adult 2015])
Microsporidiosis, disseminated (caused byTrachipleistophoraorAnncaliia) in HIV-infected patients (off-label use): Oral: 400 mg once daily in combination with albendazole (HHS [OI adult 2015])
Onychomycosis (fingernail involvement only): Oral capsule: 200 mg twice daily for 1 week; repeat 1-week course after 3-week off-time
Onychomycosis (toenails due to Trichophyton rubrum or T. mentagrophytes): Oral tablet: 200 mg once daily for 12 consecutive weeks.
Onychomycosis (toenails with or without fingernail involvement): Oral capsule: 200 mg once daily for 12 consecutive weeks
Canadian labeling (not in US labeling): "Pulse-dosing " �: 200 mg twice daily for 1 week; repeat 1-week course twice with 3-week off-time between each course
Paracoccidioidomycosis: Canadian labeling (not in US labeling): Oral capsule: 100 mg once daily for 6 months
Penicilliosis in HIV-infected patients (off-label use; HHS [OI adult 2015]): Oral:
Primary prophylaxis: 200 mg once daily for patients with a CD4 count <100 cells/mm3 who spend extensive time in northern Thailand, Vietnam, and Southern China, especially rural areas
Treatment: 200 mg twice daily for 8 weeks (mild disease) or 10 weeks (severe infections), then continue with maintenance therapy. In severely-ill patients, initiate therapy with 2 weeks of liposomal amphotericin B.
Chronic maintenance (secondary prophylaxis): 200 mg once daily until CD4 count >100 cells/mm3 for ≥6 months in response to ART
Pityriasis versicolor: Canadian labeling (not in US labeling): Oral: 200 mg once daily for 7 days
Sporotrichosis: Oral:
Lymphocutaneous: 200 mg daily for 3 to 6 months (Kauffman, 2007)
Canadian labeling (not in US labeling): 100 mg once daily for 3 months
Osteoarticular and pulmonary: 200 mg twice daily for ≥1 years (may use amphotericin B initially for stabilization) (Kauffman, 2007)
Tinea corporis or tinea cruris: Canadian labeling (not in US labeling): Oral capsule: 100 mg once daily for 14 consecutive days or 200 mg once daily for 7 consecutive days. Note: Equivalency between regimens not established.
Tinea pedis: Canadian labeling (not in US labeling): Oral capsule: 100 mg once daily for 28 consecutive days or 200 mg twice daily for 7 consecutive days. Note: Equivalency between regimens not established. Patients with chronic resistant infection may benefit from lower dose and extended treatment time (100 mg once daily for 28 days).
Refer to adult dosing.
Candidiasis:
Infants and Children (HIV-exposed/-positive; off-label use):
Oropharyngeal: Oral solution: 2.5 mg/kg/dose twice daily (maximum: 200 mg daily [400 mg daily if fluconazole-refractory]) for 7 to 14 days (CDC, 2009)
Esophageal: Oral solution: 5 mg/kg/day once daily or divided twice daily for 14 to 21 days (CDC, 2009)
Adolescents (off-label population): HIV-infected patients:
Esophageal: Oral solution: 200 mg once daily for 14 to 21 days (HHS [OI adult 2015])
Oropharyngeal (alternative to preferred therapy): Oral solution: 200 mg once daily for 7 to 14 days (HHS [OI adult 2015])
Vulvo-vaginal (uncomplicated) (off-label use): Refer to adult dosing.
Coccidioidomycosis: Infants and Children (HIV-exposed/-positive; off-label use):
Treatment: Oral: 5 to 10 mg/kg/dose twice daily for 3 days, followed by 2 to 5 mg/kg/dose orally twice daily (maximum: 400 mg daily) (CDC, 2009)
Relapse prevention: Oral: 2 to 5 mg/kg/dose twice daily (maximum: 400 mg daily) (CDC, 2009)
Coccidioidal meningitis in HIV-infected patients (off-label use) (alternative to preferred therapy): Adolescents: Refer to adult dosing.
Coccidioidal pneumonia (focal pneumonia) in HIV-infected patients (off-label use): Adolescents: Refer to adult dosing.
Cryptococcus: Infants and Children (HIV-exposed/-positive; off-label use):
Treatment, consolidation therapy: Oral solution (preferred): Initial: 2.5 to 5 mg/kg/dose 3 times daily (maximum daily dose: 600 mg daily) for 3 days (9 doses) followed by 5 to 10 mg/kg/day divided once or twice daily (maximum daily dose: 400 mg daily) for a minimum of 8 weeks (CDC, 2009)
Relapse prevention: Oral solution: 5 mg/kg/dose once daily (maximum: 200 mg daily) (CDC, 2009)
Histoplasmosis:
Infants and Children (HIV-exposed/-positive; off-label use):
Treatment of mild disseminated disease: Oral solution: 2 to 5 mg/kg/dose 3 times daily for 3 days (9 doses), followed by twice daily for 12 months (maximum: 200 mg per dose) (CDC, 2009)
Consolidation treatment for moderate-severe to severe disseminated disease, including CNS infection (following appropriate induction therapy): Oral solution: 2 to 5 mg/kg/dose 3 times daily for 3 days, followed by 2 to 5 mg/kg/dose (maximum: 200 mg per dose) twice daily for 12 months for non-CNS-disseminated disease or for ≥12 months for CNS infection (CDC, 2009)
Relapse prevention: Oral solution: 5 mg/kg/dose twice daily (maximum: 400 mg daily) (CDC, 2009)
Adolescents (off-label population): HIV-positive patients:
Treatment (off-label dose): 200 mg 3 times daily for 3 days, then 200 mg twice daily. Duration of twice daily maintenance therapy should be at least 12 months (HHS [OI adult 2015])
Primary prophylaxis in HIV-infected patients (off-label use): Refer to adult dosing.
Long-term suppression therapy (secondary prophylaxis) (off-label use): Refer to adult dosing.
Microsporidiosis, disseminated (caused byTrachipleistophoraorAnncaliia) in HIV-infected patients (off-label use): Adolescents: Refer to adult dosing.
Penicilliosis in HIV-infected patients (off-label use): Adolescents: Refer to adult dosing.
The manufacturers labeling states to use with caution in patients with renal impairment; dosage adjustment may be needed. Limited data suggest that no dosage adjustments are required in renal impairment; wide variations observed in plasma concentrations versus time profiles in patients with uremia, or receiving hemodialysis or continuous ambulatory peritoneal dialysis (Boelaert, 1988).
Hemodialysis: Nondialyzable
There are no dosage adjustments provided in the manufacturer 's labeling; however, use caution and monitor closely for signs/symptoms of toxicity.
Do not administer with antacids. Capsule and oral solution formulations are not bioequivalent and thus are not interchangeable. Capsule and tablet absorption is best if taken with food, therefore, it is best to administer itraconazole after meals at the same time each day; 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.
Capsule, tablet: Take with food.
Solution: Take without food, if possible.
Capsule: Store at room temperature of 15 � �C to 25 � �C (59 � �F to 77 � �F). Protect from light and moisture.
Oral solution: Store at ≤25 � �C (77 � �F); do not freeze.
Tablet: Store at room temperature 15 � �C to 25 � �C (59 � �F to 77 � �F); excursions are permitted between 15 � �C and 30 � �C (59 � �F and 86 � �F). Protect from light and moisture.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Sporanox: 100 mg [contains brilliant blue fcf (fd&c blue #1), d&c red #22 (eosine), fd&c blue #2 (indigotine)]
Sporanox Pulsepak: 100 mg [contains brilliant blue fcf (fd&c blue #1), d&c red #22 (eosine), fd&c blue #2 (indigotine)]
Generic: 100 mg
Solution, Oral:
Sporanox: 10 mg/mL (150 mL) [contains propylene glycol, saccharin sodium]
Tablet, Oral:
Onmel: 200 mg
Note: Commercial oral solution is available (10 mg/mL)
A 20 mg/mL oral suspension may be made with capsules. Empty the contents of forty 100 mg capsules and add 15 mL of Alcohol, USP. Let stand for 5 minutes. Crush the beads in a mortar and reduce to a fine powder. Mix while adding a 1:1 mixture of Ora-Sweet and Ora-Plus in incremental proportions to almost 200 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 200 mL. Label shake well" and "refrigerate". Stable for 56 days refrigerated.
Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.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. Avoid combination
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification
Alfuzosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. Avoid combination
Aliskiren: Itraconazole may increase the serum concentration of Aliskiren. 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. Consider therapy modification
Almotriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Almotriptan. Management: Limit initial almotriptan adult dose to 6.25 mg and maximum adult dose to 12.5 mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Consider therapy modification
Alosetron: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron. Monitor therapy
ALPRAZolam: Itraconazole may increase the serum concentration of ALPRAZolam. Avoid combination
Amphotericin B: Antifungal Agents (Azole Derivatives, Systemic) may diminish the therapeutic effect of Amphotericin B. Monitor therapy
Antacids: May decrease the serum concentration of Itraconazole. Management: Administer itraconazole at least 1 hour after and 2 hours before administration of any antacids. Itraconazole oral suspension may be less sensitive to the effects of decreased gastric acidity. 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. Consider therapy modification
Aprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Aprepitant. Avoid combination
ARIPiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: See full interaction monograph for details. Consider therapy modification
ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Please refer to the full interaction monograph for details concerning the recommended dose adjustments. Consider therapy modification
Astemizole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Astemizole. Avoid combination
Asunaprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Asunaprevir. Avoid combination
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. Consider therapy modification
Avanafil: Itraconazole may increase the serum concentration of Avanafil. 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. Avoid combination
Barnidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Barnidipine. Avoid combination
Bedaquiline: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bedaquiline. Management: Limit the duration of concomitant administration of bedaquiline with CYP3A4 inhibitors to no more than 14 days, unless the benefit of continued administration is judged to outweigh the possible risks. Monitor for toxic effects of bedaquiline. Consider therapy modification
Blonanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Blonanserin. Avoid combination
Boceprevir: Itraconazole may increase the serum concentration of Boceprevir. Boceprevir may increase the serum concentration of Itraconazole. Management: Limit maximum adult itraconazole dose to 200 mg daily in patients receiving boceprevir, due to a possible increase in itraconazole concentrations. Consider therapy modification
Bortezomib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bortezomib. Monitor therapy
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Bosentan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. Monitor therapy
Bosutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosutinib. Avoid combination
Bosutinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bosutinib. 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. Monitor therapy
Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy
Brexpiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose to 50% of usual with a strong CYP3A4 inhibitor; reduce to 25% of usual if used with both a moderate CYP3A4 inhibitor and a CYP2D6 inhibitor, or if a strong CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Consider therapy modification
Brinzolamide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brinzolamide. Monitor therapy
Bromocriptine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bromocriptine. Avoid combination
Budesonide (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Nasal). Monitor therapy
Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Oral Inhalation). Monitor therapy
Budesonide (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic). Avoid combination
Budesonide (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Topical). Management: Per US prescribing information, avoid this combination. Canadian product labeling does not recommend strict avoidance. If combined, monitor for excessive glucocorticoid effects as budesonide exposure may be increased. Consider therapy modification
BusPIRone: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of BusPIRone. Isavuconazonium considerations are addressed in separate monographs. Consider therapy modification
Busulfan: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Busulfan. Isavuconazonium considerations are addressed in separate monographs. 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. 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, cabozantinib dose adjustments are recommended and vary based on the cabozantinib product used and the indication for use. See monograph for details. Consider therapy modification
Calcifediol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Calcifediol. Monitor therapy
Calcium Channel Blockers: Antifungal Agents (Azole Derivatives, Systemic) may enhance the adverse/toxic effect of Calcium Channel Blockers. Specifically, itraconazole may enhance the negative inotropic effects of verapamil or diltiazem. Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel Blockers. Fluconazole and isavuconazonium likely exert weaker effects than other azoles and are addressed in separate monographs. Management: Concurrent use of felodipine or nisoldipine with itraconazole is specifically contraindicated. Frequent monitoring is warranted with any such combination; calcium channel blocker dose reductions may be required. Exceptions: Clevidipine. Consider therapy modification
Cannabis: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Monitor therapy
Cardiac Glycosides: Itraconazole may increase the serum concentration of Cardiac Glycosides. Management: Consider preemptive cardiac glycoside dose adjustments with initiation / changes / discontinuation of itraconazole. Consider therapy modification
Cariprazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cariprazine. Management: Cariprazine dose reductions of 50% are required; specific recommended management varies slightly for those stable on cariprazine versus those just starting cariprazine. See prescribing information or full interaction monograph for details. Consider therapy modification
Ceritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ceritinib. Management: If such combinations cannot be avoided, 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. Avoid combination
Cilostazol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving strong inhibitors of CYP3A4. Consider therapy modification
Cisapride: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Cisapride. Isavuconazonium considerations are addressed in separate monographs. Avoid combination
Clobetasone: Itraconazole may increase the serum concentration of Clobetasone. Avoid combination
CloZAPine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of CloZAPine. 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 product. Dosing recommendations for other cobicistat-containing products are not available. Consider therapy modification
Cobimetinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cobimetinib. Avoid combination
Colchicine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Colchicine. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a strong CYP3A4 inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Consider therapy modification
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Consider therapy modification
Conivaptan: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Conivaptan. Fluconazole and isavuconazonium considerations are addressed in separate monographs. Avoid combination
Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Conivaptan. Avoid combination
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Corticosteroids (Orally Inhaled): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Corticosteroids (Orally Inhaled). Management: Orally inhaled fluticasone propionate with a strong CYP3A4 inhibitor is not recommended. Exceptions: Beclomethasone (Oral Inhalation); Triamcinolone (Systemic). Monitor therapy
Corticosteroids (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Corticosteroids (Systemic). Exceptions: MethylPREDNISolone; PrednisoLONE (Systemic); PredniSONE. Monitor therapy
Crizotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Crizotinib. Avoid combination
CycloSPORINE (Systemic): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of CycloSPORINE (Systemic). Fluconazole and isavuconazonium considerations are addressed in separate monographs. Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Itraconazole. Avoid combination
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification
CYP3A4 Substrates: CYP3A4 Inhibitors (Strong) may decrease the metabolism of CYP3A4 Substrates. Exceptions: Alitretinoin (Systemic); Buprenorphine; Gefitinib; HYDROcodone; Praziquantel; Telithromycin; Vinorelbine. Consider therapy modification
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. Consider therapy modification
Dabrafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dabrafenib. Avoid combination
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. No dose adjustment is needed when daclatasvir is used with darunavir/cobicistat. Consider therapy modification
Dapoxetine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dapoxetine. Avoid combination
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. Consider therapy modification
Dasatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dasatinib. Management: Use of this combination should be avoided; consider reducing dasatinib dose if a strong CYP3A4 inhibitor must be used. If using dasatinib 100 mg/day, consider reduction to 20 mg/day; if using dasatinib 140 mg/day, consider reduction to 40 mg/day. Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Didanosine: May decrease the absorption of Antifungal Agents (Azole Derivatives, Systemic). Enteric coated didanosine capsules are not expected to affect these antifungals. Consider therapy modification
Dienogest: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dienogest. Monitor therapy
Dihydroergotamine: Itraconazole may increase the serum concentration of Dihydroergotamine. Avoid combination
Disopyramide: Itraconazole may increase the serum concentration of Disopyramide. Avoid combination
DOCEtaxel: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of DOCEtaxel. Fluconazole and isavuconazonium considerations are addressed in separate monographs. Consider therapy modification
Dofetilide: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Dofetilide. Avoid combination
Domperidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Domperidone. Avoid combination
Doxercalciferol: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Doxercalciferol. Monitor therapy
DOXOrubicin (Conventional): CYP3A4 Inhibitors (Strong) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong CYP3A4 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Dronabinol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronabinol. Monitor therapy
Dronedarone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone. Avoid combination
Drospirenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Drospirenone. Monitor therapy
Dutasteride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride. Monitor therapy
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification
Efavirenz: May decrease the serum concentration of Itraconazole. Avoid combination
Eletriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eletriptan. Avoid combination
Eliglustat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eliglustat. Management: Use should be avoided under some circumstances. See full drug interaction monograph for details. Consider therapy modification
Elvitegravir: Itraconazole may increase the serum concentration of Elvitegravir. Management: Limit itraconazole to a maximum dose of 200 mg/day in patients who are being treated with the elvitegravir-containing products. Consider therapy modification
Eplerenone: Itraconazole may increase the serum concentration of Eplerenone. Avoid combination
Ergoloid Mesylates: Itraconazole may increase the serum concentration of Ergoloid Mesylates. Avoid combination
Ergonovine: Itraconazole may increase the serum concentration of Ergonovine. Avoid combination
Ergotamine: Itraconazole may increase the serum concentration of Ergotamine. 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 severe adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). Consider therapy modification
Estazolam: Itraconazole may increase the serum concentration of Estazolam. Avoid combination
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). Consider therapy modification
Etizolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Etizolam. Management: Consider use of lower etizolam doses when using this combination; specific recommendations concerning dose adjustment are not available. Monitor clinical response to the combination closely. Consider therapy modification
Etravirine: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Etravirine. Applicable Isavuconazonium considerations are addressed in separate monographs. Etravirine may decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). This would be anticipated with itraconazole or ketoconazole. Etravirine may increase the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). This would be anticipated with voriconazole. Management: Monitor for increased effects/toxicity of etravirine. Antifungal dose adjustment may be needed for ketoconazole, itraconazole, or posaconazole but specific dosing guidelines are lacking. Consider therapy modification
Everolimus: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. Avoid combination
Felodipine: Itraconazole may increase the serum concentration of Felodipine. Avoid combination
FentaNYL: CYP3A4 Inhibitors (Strong) may increase the serum concentration of FentaNYL. Management: Monitor patients closely for several days following initiation of this combination, and adjust fentanyl dose as necessary. Consider therapy modification
Fesoterodine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Management: Avoid fesoterodine doses greater than 4 mg daily in adult patients who are also receiving strong CYP3A4 inhibitors. Consider therapy modification
Fexofenadine: Itraconazole may increase the serum concentration of Fexofenadine. Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Flibanserin. Avoid combination
Fluticasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Nasal). Monitor therapy
Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Management: Use of orally inhaled fluticasone propionate with strong CYP3A4 inhibitors is not recommended. Use of orally inhaled fluticasone furoate with strong CYP3A4 inhibitors should be done with caution. Monitor patients using such a combination more closely. Consider therapy modification
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. Consider therapy modification
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Gefitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Gefitinib. Monitor therapy
Grapefruit Juice: May decrease the serum concentration of Itraconazole. Grapefruit Juice may increase the serum concentration of Itraconazole. Monitor therapy
GuanFACINE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of GuanFACINE. Management: Reduce the guanfacine dose by 50% when initiating this combination. Consider therapy modification
H2-Antagonists: May decrease the serum concentration of Itraconazole. Management: When this combination is used, the itraconazole should be administered with a cola beverage (8 ounces). Itraconazole oral suspension may be less sensitive to this interaction. Monitor patient response to itraconazole closely. Consider therapy modification
Halofantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Halofantrine. Avoid combination
Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification
HYDROcodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of HYDROcodone. Monitor therapy
Ibrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ibrutinib. Management: If a strong CYP3A inhibitor must be used short-term (e.g. antifungals and antibiotics for 7 days or less), consider stopping ibrutinib until the CYP3A inhibitor is no longer needed. Avoid combination
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Ifosfamide: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. 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. Consider therapy modification
Imatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imatinib. Monitor therapy
Imidafenacin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imidafenacin. Monitor therapy
Indinavir: Itraconazole may increase the serum concentration of Indinavir. Indinavir may increase the serum concentration of Itraconazole. Management: Reduce the normal indinavir adult dose to 600 mg every 8 hours when given with itraconazole. Monitor for increased systemic effects (including adverse/toxic effects) of itraconazole. Consider therapy modification
Irinotecan Products: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan Products. Avoid combination
Isavuconazonium Sulfate: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Strong) may increase isavuconazole serum concentrations. Management: Combined use is considered contraindicated per US labeling. Lopinavir/ritonavir (and possibly other uses of ritonavir doses less than 400 mg every 12 hours) is treated as a possible exception to this contraindication despite strongly inhibiting CYP3A4. Avoid combination
Isoniazid: May decrease the serum concentration of Itraconazole. Monitor therapy
Ivabradine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivabradine. Avoid combination
Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult prescribing information for specific age- and weight-based recommendations. Consider therapy modification
Ixabepilone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone. Consider therapy modification
Lacosamide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lacosamide. Monitor therapy
Lapatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lapatinib. Management: If an overlap in therapy cannot be avoided, consider reducing lapatinib adult dose to 500 mg/day during, and within 1 week of completing, treatment with the strong CYP3A4 inhibitor. Avoid combination
Lercanidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lercanidipine. Avoid combination
Levobupivacaine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine. Monitor therapy
Levomilnacipran: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levomilnacipran. Management: Do not exceed a maximum adult levomilnacipran dose of 80 mg/day in patients also receiving strong CYP3A4 inhibitors. Consider therapy modification
Lomitapide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lomitapide. Avoid combination
Lopinavir: May increase the serum concentration of Itraconazole. Management: Limit the adult maximum itraconazole dose to 200 mg/day in patients receiving lopinavir/ritonavir. Consider therapy modification
Losartan: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Losartan. Applicable Isavuconazonium considerations are addressed in separate monographs. Monitor therapy
Lovastatin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lovastatin. Avoid combination
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Lumacaftor: May decrease the serum concentration of Itraconazole. Avoid combination
Lurasidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurasidone. Avoid combination
Macitentan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Macitentan. Avoid combination
Maraviroc: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. Management: Reduce the adult dose of maraviroc to 150 mg twice daily when used with a strong CYP3A4 inhibitor. Do not use maraviroc with strong CYP3A4 inhibitors in patients with Clcr less than 30 mL/min. Consider therapy modification
MedroxyPROGESTERone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MedroxyPROGESTERone. Monitor therapy
Meloxicam: Itraconazole may decrease the serum concentration of Meloxicam. Monitor therapy
Methadone: Itraconazole may increase the serum concentration of Methadone. Avoid combination
Methylergonovine: Itraconazole may increase the serum concentration of Methylergonovine. Avoid combination
MethylPREDNISolone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose reduction in patients receiving strong CYP3A4 inhibitors and monitor for increased steroid related adverse effects. Consider therapy modification
Midazolam: Itraconazole may increase the serum concentration of Midazolam. Management: Oral midazolam is contraindicated. Use intravenous midazolam with great caution in patients receiving itraconazole, employing reduced initial doses whenever possible and monitoring closely for enhanced and prolonged effects. Avoid combination
MiFEPRIStone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MiFEPRIStone. Management: Limit mifepristone adult dose, when used for treatment of hyperglycemia in Cushings syndrome, to a maximum of 300 mg/day when combined with a strong CYP3A4 inhibitor. Monitor for increased mifepristone toxicity regardless of dose or indication. Consider therapy modification
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. 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. Consider therapy modification
Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy
Naloxegol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naloxegol. Avoid combination
Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Nevirapine: May decrease the serum concentration of Itraconazole. Avoid combination
Nilotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib. Avoid combination
NiMODipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NiMODipine. Avoid combination
Nintedanib: Combined Inhibitors of CYP3A4 and P-glycoprotein may increase the serum concentration of Nintedanib. Monitor therapy
Nisoldipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. Avoid combination
Olaparib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Olaparib. Management: Avoid use of strong CYP3A4 inhibitors in patients being treated with olaparib. If such concurrent use cannot be avoided, the dose of olaparib should be reduced to 150 mg twice daily. Avoid combination
Osimertinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Osimertinib. Avoid combination
Ospemifene: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ospemifene. Monitor therapy
Oxybutynin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Oxybutynin. 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. Consider therapy modification
Palbociclib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Palbociclib. Avoid combination
Paliperidone: Itraconazole may enhance the QTc-prolonging effect of Paliperidone. Itraconazole may decrease the metabolism of Paliperidone. Consider therapy modification
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. Consider therapy modification
Parecoxib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Parecoxib. Monitor therapy
Paricalcitol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Paricalcitol. Monitor therapy
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination
P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
Pimavanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimavanserin. Consider therapy modification
Pimecrolimus: CYP3A4 Inhibitors (Strong) may decrease the metabolism of Pimecrolimus. Monitor therapy
Pimozide: Antifungal Agents (Azole Derivatives, Systemic) may enhance the arrhythmogenic effect of Pimozide. Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Pimozide. This increase in serum concentrations may lead to QTc interval prolongation and ventricular arrhythmias. Applicable Isavuconazonium considerations are addressed in separate monographs. Avoid combination
Pimozide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimozide. Avoid combination
PONATinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of PONATinib. Management: Per ponatinib U.S. prescribing information, the adult starting dose of ponatinib should be reduced to 30 mg daily during treatment with any strong CYP3A4 inhibitor. Consider therapy modification
Pranlukast: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pranlukast. Monitor therapy
Prasugrel: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Prasugrel. Monitor therapy
Pravastatin: Itraconazole may increase the serum concentration of Pravastatin. Monitor therapy
Praziquantel: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Praziquantel. Monitor therapy
PrednisoLONE (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of PrednisoLONE (Systemic). Monitor therapy
PredniSONE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of PredniSONE. Monitor therapy
Propafenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Propafenone. Monitor therapy
Proton Pump Inhibitors: May decrease the serum concentration of Itraconazole. Consider therapy modification
Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Monitor therapy
QUEtiapine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of QUEtiapine. Management: In quetiapine treated patients, reduce the quetiapine dose to one sixth of the regular dose following strong CYP3A4 inhibitor initiation. In patients receiving strong CYP3A4 inhibitors, initiate quetiapine at the lowest dose and up-titrate as needed. Consider therapy modification
QuiNIDine: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of QuiNIDine. Applicable Isavuconazonium considerations are addressed in separate monographs. Avoid combination
Ramelteon: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ramelteon. Monitor therapy
Ranolazine: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Ranolazine. Fluconazole and isavuconazonium considerations are addressed in separate monographs. Avoid combination
Ranolazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. Avoid combination
Reboxetine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Reboxetine. Consider therapy modification
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. Avoid combination
Regorafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Regorafenib. Avoid combination
Repaglinide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Repaglinide. Management: The addition of a CYP2C8 inhibitor to this drug combination may substantially increase the magnitude of increase in repaglinide exposure. Monitor therapy
Retapamulin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Retapamulin. Management: Avoid this combination in patients less than 2 years old. No action is required in other populations. Monitor therapy
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy
Rilpivirine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rilpivirine. Monitor therapy
Riociguat: Itraconazole may increase the serum concentration of Riociguat. Management: Consider starting with a reduced riociguat dose of 0.5 mg three times a day. Patients receiving such a combination should also be monitored extra closely for signs or symptoms of hypotension. Consider therapy modification
Ritonavir: May increase the serum concentration of Itraconazole. Management: Limit the adult maximum itraconazole dose to 200 mg/day in patients receiving ritonavir. Consider therapy modification
Rivaroxaban: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Rivaroxaban. Avoid combination
RomiDEPsin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of RomiDEPsin. Monitor therapy
Rosuvastatin: Itraconazole may increase the serum concentration of Rosuvastatin. Monitor therapy
Ruxolitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib. Management: This combination should be avoided under some circumstances. See monograph for details. Consider therapy modification
Saccharomyces boulardii: Antifungal Agents (Systemic, Oral) may diminish the therapeutic effect of Saccharomyces boulardii. Avoid combination
Salmeterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol. 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. Consider therapy modification
SAXagliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SAXagliptin. Management: Saxagliptin U.S. product labeling recommends limiting saxagliptin adult dose to 2.5 mg/day when used with a strong CYP3A4 inhibitor. Monitor for increased saxagliptin levels/effects. A similar recommendation is not made in the Canadian product labeling. Consider therapy modification
Sildenafil: Itraconazole may increase the serum concentration of Sildenafil. Management: Concurrent itraconazole is not recommended when sildenafil is used for treatment of pulmonary arterial hypertension. If sildenafil is used to treat erectile dysfunction, an initial dose of 25 mg is recommended with concurrent itraconazole. Consider therapy modification
Silodosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin. Avoid combination
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Avoid combination
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simeprevir. Avoid combination
Simvastatin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simvastatin. Avoid combination
Sirolimus: Itraconazole may increase the serum concentration of Sirolimus. Management: Sirolimus dose adjustments will likely be needed when starting/stopping any azole antifungal. Clinical data suggest sirolimus (adult) dose reductions of 50-90% will be needed when starting an azole antifungal, but specific guidelines are lacking. Consider therapy modification
Solifenacin: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Solifenacin. Applicable Isavuconazonium considerations are addressed in separate monographs. Consider therapy modification
Sonidegib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sonidegib. Avoid combination
SORAfenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SORAfenib. Monitor therapy
St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
SUNItinib: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of SUNItinib. Applicable Isavuconazonium considerations are addressed in separate monographs. Consider therapy modification
Suvorexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Suvorexant. Avoid combination
Tacrolimus (Systemic): Itraconazole may increase the serum concentration of Tacrolimus (Systemic). Management: Monitor tacrolimus concentrations closely and adjust dose as necessary when concomitantly administered with itraconazole. Tacrolimus dose reductions will likely be required. The magnitude of this interaction may be greater in older patients. Consider therapy modification
Tacrolimus (Topical): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Tacrolimus (Topical). Applicable Isavuconazonium considerations are addressed in separate monographs. Monitor therapy
Tadalafil: Itraconazole may increase the serum concentration of Tadalafil. Consider therapy modification
Tamsulosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. Avoid combination
Tasimelteon: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tasimelteon. Monitor therapy
Telaprevir: May increase the serum concentration of Itraconazole. Itraconazole may increase the serum concentration of Telaprevir. Management: Doses of itraconazole greater than 200 mg/day are not recommended in patients receiving telaprevir. Use extra caution when using these drugs in combination. Consider therapy modification
Telithromycin: Itraconazole may increase the serum concentration of Telithromycin. Telithromycin may increase the serum concentration of Itraconazole. Avoid combination
Temsirolimus: Itraconazole may increase serum concentrations of the active metabolite(s) of Temsirolimus. Management: Consider temsirolimus dose reductions or alternatives to itraconazole. Monitor sirolimus concentrations in all patients receiving itraconazole or any systemic azole antifungal. Consider therapy modification
Terfenadine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Terfenadine. Avoid combination
Tetrahydrocannabinol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy
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. Avoid combination
Tipranavir: May increase the serum concentration of Itraconazole. Management: Limit itraconazole adult maximum dose to 200 mg/day in patients treated with tipranavir. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Tofacitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tofacitinib. Management: Reduce the adult dose of tofacitinib to 5 mg daily in patients receiving strong CYP3A4 inhibitors. Consider therapy modification
Tolterodine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolterodine. Management: The maximum recommended adult dose of tolterodine is 2 mg/day when used together with a strong CYP3A4 inhibitor. Consider therapy modification
Tolvaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan. Avoid combination
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination
Toremifene: CYP3A4 Inhibitors (Strong) may enhance the adverse/toxic effect of Toremifene. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene. Avoid combination
Trabectedin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Trabectedin. Avoid combination
TraMADol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraMADol. Monitor therapy
Triazolam: Itraconazole may increase the serum concentration of Triazolam. Avoid combination
Udenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Udenafil. Avoid combination
Ulipristal: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combo should be monitored for ulipristal toxicity. Avoid combination
Vardenafil: Itraconazole may increase the serum concentration of Vardenafil. Management: Limit vardenafil dosing to a maximum of 5 mg per 24 hours in patients receiving itraconazole 200 mg/day, and a maximum of 2.5 mg per 24 hours in patients receiving itraconazole 400 mg/day. Consider therapy modification
Vemurafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vemurafenib. Avoid combination
Venetoclax: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Venetoclax. Management: These combinations are contraindicated during venetoclax initiation and ramp-up. In patients receiving steady venetoclax doses after completing ramp-up, reduce the venetoclax by at least 75% if strong CYP3A4 inhibitor use cannot be avoided. Consider therapy modification
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification
Vilazodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. Management: Limit maximum adult vilazodone dose to 20 mg/day in patients receiving strong CYP3A4 inhibitors. The original vilazodone dose can be resumed following discontinuation of the strong CYP3A4 inhibitor. Consider therapy modification
VinBLAStine: Itraconazole may increase the serum concentration of VinBLAStine. Monitor therapy
VinCRIStine: Itraconazole may enhance the adverse/toxic effect of VinCRIStine. Itraconazole may increase the serum concentration of VinCRIStine. Consider therapy modification
VinCRIStine (Liposomal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination
Vindesine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vindesine. Monitor therapy
Vinflunine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinflunine. Avoid combination
Vinorelbine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinorelbine. Monitor therapy
Vitamin K Antagonists (eg, warfarin): Itraconazole may increase the serum concentration of Vitamin K Antagonists. Monitor therapy
Vorapaxar: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vorapaxar. Avoid combination
Zolpidem: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Zolpidem. Applicable Isavuconazonium considerations are addressed in separate monographs. Monitor therapy
Zopiclone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zopiclone. Management: The initial starting adult dose of zopiclone should not exceed 3.75 mg if combined with a strong CYP3A4 inhibitor. Monitor patients for signs and symptoms of zopiclone toxicity if these agents are combined. Consider therapy modification
Zuclopenthixol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zuclopenthixol. Management: Consider zuclopenthixol dosage reduction with concomitant use of a strong CYP3A4 inhibitor (eg, ketoconazole) in poor CYP2D6 metabolizers or with strong CYP2D6 inhibitors (eg, paroxetine). Monitor for increased zuclopenthixol levels/toxicity. Consider therapy modification
Liver function in patients with preexisting hepatic dysfunction, and in all patients being treated for longer than 1 month; serum concentrations when clinically indicated (due to erratic bioavailability with oral formulations); renal function; signs/symptoms of CHF
>10%: Gastrointestinal: Diarrhea (2% to 11%), nausea (2% to 11%)
1% to 10%:
Cardiovascular: Edema (4%), chest pain (3%), hypertension (2% to 3%),
Central nervous system: Headache (1% to 10%), dizziness (1% to 4%), anxiety (3%), depression (2% to 3%), fatigue (2% to 3%), pain (2% to 3%), malaise (1% to 3%), abnormal dreams (2%)
Dermatologic: Skin rash (3% to 9%), pruritus ( ≤5%), diaphoresis (3%)
Endocrine & metabolic: Hypertriglyceridemia ( ≤3%), hypokalemia (2%)
Gastrointestinal: Vomiting (5% to 7%), abdominal pain (2% to 6%), dyspepsia ( ≤4%), flatulence ( ≤4%), gastrointestinal disease ( ≤4%), gingivitis (3%), aphthous stomatitis ( ≤3%), constipation (2% to 3%), gastritis (2%), gastroenteritis (2%), increased appetite (2%)
Genitourinary: Cystitis (3%), urinary tract infection (1% to 3%)
Hepatic: Abnormal hepatic function tests ( ≤4%), increased liver enzymes (3% to 4%)
Infection: Herpes zoster (2%)
Neuromuscular & skeletal: Bursitis (3%), myalgia ( ≤3%), tremor (2%), weakness ( ≤2%)
Respiratory: Rhinitis (5% to 9%), upper respiratory tract infection (6% to 8%), sinusitis (2% to 7%), cough (1% to 4%), dyspnea (2%), increased bronchial secretions (2%), pneumonia (2%), pharyngitis ( ≤2%)
Miscellaneous: Fever (2% to 7%)
<2% (Limited to important or life-threatening): Abnormal urinalysis, acute generalized exanthematous pustulosis, adrenal insufficiency, albuminuria, anaphylactoid reaction, anaphylaxis, angioedema, cardiac arrhythmia, cardiac failure, confusion, congestive heart failure, dehydration, dysphagia, erythema multiforme, erythematous rash, exfoliative dermatitis, gastrointestinal disease, gynecomastia, hearing loss, hematuria, hepatic failure, hepatitis, hepatotoxicity, hyperbilirubinemia, hyperglycemia, hyperhidrosis, hyperkalemia, hypersensitivity angiitis, hypersensitivity reaction, hypomagnesemia, increased blood urea nitrogen, increased creatine phosphokinase, increased gamma-glutamyl transferase, increased lactate dehydrogenase, increased serum alkaline phosphatase, increased serum ALT, increased serum AST, left heart failure, leukopenia, menstrual disease, mucosal inflammation, neutropenia, orthostatic hypotension, pancreatitis, paresthesia, peripheral edema, pollakiuria, pulmonary edema, renal insufficiency, rigors, serum sickness, sinus bradycardia, Stevens-Johnson syndrome, tachycardia, thrombocytopenia, toxic epidermal necrolysis, vasculitis, voice disorder
Bioavailability is slightly reduced.
Cmax was reduced by 47% and resulted in a twofold increase in half-life (capsules).
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.
- Heart failure:[US Boxed Warning]: Negative inotropic effects have been observed following intravenous administration. Discontinue or reassess use if signs or symptoms of heart failure (HF) occur during treatment. CHF has been reported, particularly in patients receiving a total daily oral dose of 400 mg. Use with caution in patients with risk factors for HF (COPD, renal failure, edematous disorders, ischemic or valvular disease). Discontinue treatment if signs or symptoms of heart failure develop.
- Hepatotoxicity: Rare cases of serious hepatotoxicity (including liver failure and death) have been reported (including some cases occurring within the first week of therapy); hepatotoxicity was reported in some patients without pre-existing liver disease or risk factors. Use with caution in patients with preexisting hepatic impairment; monitor liver function closely and dosage adjustment may be warranted. 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. Discontinue treatment if signs or symptoms of hepatotoxicity develop.
- Hypersensitivity: Use caution in patients with a history of hypersensitivity to other azoles.
- Neuropathy: Discontinue if signs or symptoms of neuropathy occur during treatment.
Disease-related concerns:
- Cystic fibrosis: Large differences in itraconazole pharmacokinetic parameters have been observed in cystic fibrosis patients receiving the solution; if a patient with cystic fibrosis does not respond to therapy, alternate therapies should be considered.
- Dermatomycosis: The Canadian labeling contraindicates use in the treatment of dermatomycoses (tinea corporis, tinea cruris, tinea pedis, pityriasis versicolor) in women who are pregnant or intend to become pregnant and in patients with evidence of ventricular dysfunction or a history of HF.
- Onychomycosis: [US Boxed Warning]: Use is contraindicated for treatment of onychomycosis in patients with ventricular dysfunction or a history of HF. Cases of HF, peripheral edema, and pulmonary edema have occurred in this patient population. Due to potential toxicity, 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.
Concurrent drug therapy issues:
- Drug-drug interactions: Additional potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
- High potential for interactions: [US Boxed Warning]: Coadministration with itraconazole can cause elevated plasma concentrations of certain drugs and can lead to QT prolongation and ventricular tachyarrhythmias, including torsades de pointes. Coadministration with methadone, disopyramide, dofetilide, dronedarone, quinidine, ergot alkaloids, irinotecan, lurasidone, oral midazolam, pimozide, triazolam, felodipine, nisoldipine, ranolazine, eplerenone, cisapride, lovastatin, simvastatin, ticagrelor and, in subjects with varying degrees of renal or hepatic impairment, colchicine, fesoterodine, telithromycin, and solifencacin is contraindicated.
Dosage form specific issues:
- Oral capsules/tablets: Absorption of itraconazole capsules is reduced when gastric acidity is reduced (eg, achlorhydria, acid suppressive therapy) administer capsules or tablets with an acidic beverage (eg, cola) in patients with reduced gastric acidity and separate administration from acid suppressive therapy (refer to drug interactions section). Monitor for response.
- 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).
- Product interchangeability: Due to differences in bioavailability, oral capsules and oral solution 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. Itraconazole oral solution and capsule formulations are not bioequivalent or interchangeable. Due to variable bioavailability of oral preparations, therapeutic drug monitoring is advisable (Walsh, 2008).
C
Dose related adverse events were observed in animal reproduction studies. Use is contraindicated for the treatment of onychomycosis during pregnancy. If used for the treatment of onychomycosis in women of reproductive potential, effective contraception should be used during treatment and for 2 months following treatment. Therapy should begin on the second or third day following menses. Congenital abnormalities have been reported during postmarketing surveillance, but a causal relationship has not been established. The Canadian labeling contraindicates use in the treatment of onychomycosis or dermatomycoses (tinea corporis, tinea cruris, tinea pedis, pityriasis versicolor) in women who are pregnant or intend to become pregnant.
Interferes with cytochrome P450 activity, decreasing ergosterol synthesis (principal sterol in fungal cell membrane) and inhibiting cell membrane formation
Requires gastric acidity; capsule or tablet better absorbed with food, solution better absorbed on empty stomach
Vd (average): >700 L; 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
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.
Urine (<0.03% active drug, 35% as inactive metabolites); feces (54%; ~3% to 18% as unchanged drug)
Plasma: Capsules/tablets: 2 to 5 hours; Oral solution: 2.5 hours
Children (6 months to 12 years): Oral solution: ~36 hours; Metabolite hydroxy-itraconazole: ~18 hours
Adults: Oral: Single dose: 16 to 28 hours, Multiple doses: 34 to 42 hours; Cirrhosis (single dose): 37 hours (range: 20 to 54 hours)
Plasma: 99.8%; metabolite hydroxy-itraconazole: 99.6%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache, abdominal pain, nausea, vomiting, diarrhea, flatulence, rhinorrhea, or bad taste in mouth. Have patient report immediately to prescriber signs of heart problems (cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than 5 pounds in 24 hours, dizziness, or passing out), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of a pancreas problem (pancreatitis; severe abdominal pain, severe back pain, severe nausea, vomiting), burning or numbness feeling, blood in urine, breast pain, enlarged breasts, urinary retention, change in amount of urine passed, angina, tachycardia, sexual dysfunction, depression, dysphagia, severe dizziness, passing out, chills, pharyngitis, alopecia, joint pain, tinnitus, tremors, insomnia, bruising, bleeding, dry mouth, dry eyes, vision changes, loss of strength and energy, or hearing impairment (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.