itraconazole (Rx)

Brand and Other Names:Sporanox, Onmel, more...Tolsura
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 65mg (Tolsura)
  • 100mg (Sporanox, generic)

oral solution

  • 10mg/mL (Sporanox, generic)

tablet

  • 200mg (Onmel)

Life-threatening Infections

Recommended loading dose based on pharmacokinetic data

Sporanox

  • Loading dose: 200 mg (2 capsules) PO TID (600 mg/day) for the first 3 days, followed by recommended dosing based on indication

Tolsura

  • Loading dose: 130 mg (2 x 65 mg capsules) PO TID (390 mg/day) for the first 3 days, followed by recommended dosing based on indication

Continue for a minimum of 3 months and until active fungal infection has subsided; an inadequate period of treatment may lead to recurrence of active infection

Blastomycosis

Indicated for treatment of blastomycosis, including pulmonary and extrapulmonary infections in immunocompromised and nonimmunocompromised adults

Sporanox

  • 200 mg PO qDay
  • If no improvement, or evidence of progressive fungal disease, increase dose in 100-mg increments to a maximum of 400 mg/day
  • Divide doses >200 mg/day into 2 doses

Tolsura

  • 130 mg PO qDay
  • If no improvement, or evidence of progressive fungal disease, increase dose in 65 mg increments to a maximum of 260 mg/day (130 mg BID)
  • Divide doses >130 mg/day into 2 doses

Aspergillosis

Indicated for treatment of pulmonary and extrapulmonary aspergillosis in immunocompromised and nonimmunocompromised adults who are intolerant of or refractory to amphotericin B therapy

Sporanox

  • 200-400 mg/day PO; may be used in combination with corticosteroids

Tolsura

  • 130 mg PO qDay or BID

Histoplasmosis

Indicated for treatment of histoplasmosis, including chronic cavitary pulmonary disease and disseminated, nonmeningeal histoplasmosis in immunocompromised and nonimmunocompromised adults

Sporanox

  • 200 mg PO qDay
  • If no improvement, or evidence of progressive fungal disease, increase dose in 100-mg increments to a maximum of 400 mg/day
  • Divide doses >200 mg/day into 2 doses

Tolsura

  • 130 mg PO qDay
  • If no improvement, or evidence of progressive fungal disease, increase dose in 65 mg increments to a maximum of 260 mg/day (130 mg BID)
  • Divide doses >130 mg/day into 2 doses

Onychomycosis

Indicated for treatment of onychomycosis of the toenail due to Trichophyton rubrum or T. mentagrophytes in nonimmunocompromised patients

Fingernails (Sporanox only): 2 treatment pulses, each consisting of 200 mg q12hr for 1 week; pulses are separated by a 3-week period without Sporanox

Toenails, with or without fingernail involvement (Sporanox, Onmel): 200 mg/day PO for 12 weeks

Candidiasis

Indicated for treatment of oropharyngeal and esophageal candidiasis

Esophageal candidiasis

  • 100 mg (10 mL) PO qDay for a minimum of 3 weeks; continue treatment for 2 weeks following resolution of symptoms
  • Doses ≤200 mg/day (20 mL) may be used based on medical judgment of the patient’s response to therapy

Oropharyngeal candidiasis

  • Oral solution only: 200 mg (20 mL) PO qDay for 1-2 weeks; signs and symptoms of oropharyngeal candidiasis generally resolve within several days
  • Unresponsive/refractory to fluconazole: 100 mg (10 mL) PO BID
  • Clinical response will be seen in 2-4 weeks
  • May be expected to relapse shortly after discontinuing therapy
  • Limited data on safety of long-term use (>6 months) of oral solution are available at this time

Otomycosis (Orphan)

Suspension: Topical treatment of fungal otitis externa (otomycosis)

Orphan indication sponsor

  • Fairfield Clinical Trials, LLC; 200 Steep Hill Road; Weston, CT 06883

Dosage Modifications

Renal impairment

  • Limited data are available on use of oral itraconazole in patients with renal impairment
  • Exercise caution when administered in this patient population

Hepatic impairment

  • Limited data are available on use of oral itraconazole in patients with hepatic impairment
  • Tolsura: In patients with elevated or abnormal liver enzymes or active liver disease, or who have experienced liver toxicity with other drugs, treatment is strongly discouraged unless there is a serious or life-threatening situation where the expected benefit exceeds the risk; monitor liver function

Dosing Considerations

In some immunocompromised patients (e.g., neutropenic, AIDS or organ transplant patients), oral bioavailability for drug may be decreased; adjust dose based on clinical response in these patients

Do not use Sporanox capsules and oral solution interchangeably; only the oral solution has been demonstrated effective for oral and/or esophageal candidiasis

Limitations of use (Tolsura)

  • Not indicated for onychomycosis
  • NOT interchangeable or substitutable with other itraconazole products due to differences in dosing; follow specific dosage recommendations for Tolsura

Safety and efficacy not established

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Interactions

Interaction Checker

and itraconazole

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            Contraindicated (42)

            • alfuzosin

              itraconazole increases levels of alfuzosin by decreasing metabolism. Contraindicated.

            • avanafil

              itraconazole will increase the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration with strong CYP3A4 is contraindicated during and 2 weeks after itraconazole.

            • conivaptan

              conivaptan will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Not recommended during, and 2 weeks after itraconazole.

            • dihydroergotamine

              itraconazole will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increased risk of ergotism leading to cerebral ischemia and/or ischemia of the extremities

            • dihydroergotamine intranasal

              itraconazole will increase the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increased risk of ergotism leading to cerebral ischemia and/or ischemia of the extremities

            • disopyramide

              itraconazole will increase the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

              disopyramide and itraconazole both increase QTc interval. Contraindicated.

            • dofetilide

              dofetilide and itraconazole both increase QTc interval. Contraindicated.

              itraconazole will increase the level or effect of dofetilide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Both drugs will increase QT interval

            • dronedarone

              itraconazole will increase the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated during and 2 weeks after itraconazole treatment.

            • eliglustat

              itraconazole will increase the level or effect of eliglustat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors are contraindicated with eliglustat poor or intermediate metabolizers; reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive metabolizers; eliglustat is contraindiated if strong or moderate CYP2D6 inhibitors are given concomitantly with strong or moderate CYP3A inhibitors

            • eplerenone

              itraconazole will increase the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. May increase the risk of hyperkalemia and hypotension

            • ergoloid mesylates

              itraconazole will increase the level or effect of ergoloid mesylates by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • ergotamine

              itraconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increased risk of ergotism leading to cerebral ischemia and/or ischemia of the extremities

            • estazolam

              itraconazole will increase the level or effect of estazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • felodipine

              felodipine will increase the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

              itraconazole will increase the level or effect of felodipine by Other (see comment). Contraindicated. CCBs elicit negative inotropic effects which may be additive to those of itraconazole; additionally, itraconazole can inhibit the metabolism of calcium channel blockers. Coadministration is contraindicated during and 2 weeks after itraconazole treatment.

            • fesoterodine

              itraconazole will increase the level or effect of fesoterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration in patients with renal or hepatic impairment may result in increased fesoterodine levels and increased risk for potentially fatal adverse events.

            • finerenone

              itraconazole will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • flibanserin

              itraconazole will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of flibanserin with moderate or strong CYP3A4 inhibitors is contraindicated. Severe hypotension or syncope can occur.

            • indapamide

              indapamide and itraconazole both increase QTc interval. Contraindicated.

            • irinotecan

              itraconazole will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 Inhibitors may increase the serum concentration of SN-38 (active metabolite for irinotecan products). Contraindicated during and 2 weeks after itraconazole treatment.

            • irinotecan liposomal

              itraconazole will increase the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated during and 2 weeks after itraconazole treatment. Strong CYP3A4 Inhibitors may increase the serum concentration of SN-38 (active metabolite for irinotecan products).

            • ivabradine

              itraconazole will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with itraconazole is contraindicated during and 2 weeks after of itraconazole treatment.

            • lomitapide

              itraconazole increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of lomitapide with itraconazole is contraindicated during and 2 weeks after of itraconazole treatment.

            • lonafarnib

              itraconazole will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inhibitors is contraindicated.

            • lovastatin

              itraconazole will increase the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of lovastatin with itraconazole is contraindicated during and 2 weeks after of itraconazole treatment.

            • lurasidone

              itraconazole will increase the level or effect of lurasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of lurasidone and strong CYP3A4 inhibitors is contraindicated.

            • methadone

              itraconazole will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. QT interval prolongation and serious arrhythmia (torsades de pointes) have occurred in patients using methadone concomitantly with oral itraconazole and/or other CYP3A4 inhibitors.

            • methylergonovine

              itraconazole increases effects of methylergonovine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increased risk of ergotism leading to cerebral ischemia and/or ischemia of the extremities.

            • midazolam

              itraconazole will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of oral midazolam and itraconazole is contraindicated during and 2 weeks after itraconazole treatment. Use IV midazolam with great caution in patients receiving itraconazole, consider reduced initial doses whenever possible and closely monitor.

            • naloxegol

              itraconazole will increase the level or effect of naloxegol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of naloxegol with strong CYP3A4 inhibitors can significantly increase naloxegol systemic exposure which may precipitate opioid withdrawal symptoms

            • nisoldipine

              itraconazole will increase the level or effect of nisoldipine by Other (see comment). Contraindicated. CCBs elicit negative inotropic effects which may be additive to those of itraconazole; additionally, itraconazole can inhibit the metabolism of calcium channel blockers. Coadministration is contraindicated during and 2 weeks after itraconazole treatment.

            • pimozide

              itraconazole will increase the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Both drugs will increase QT interval. Coadministration of pimozide and itraconazole is contraindicated during and 2 weeks after itraconazole treatment.

            • quinidine

              itraconazole will increase the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Both drugs will increase QT interval. Coadministration of quinidine and itraconazole is contraindicated during and 2 weeks after itraconazole treatment.

              quinidine will increase the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Contraindicated. Both drugs will increase QT interval

              quinidine and itraconazole both increase QTc interval. Contraindicated.

            • ranolazine

              itraconazole will increase the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. May increase risk of cardiovascular events, including prolonged QTc. Coadministration of ranolazine and itraconazole is contraindicated during and 2 weeks after itraconazole treatment.

              ranolazine will increase the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

            • silodosin

              itraconazole will increase the level or effect of silodosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Not recommended during and 2 weeks after itraconazole treatment.

              itraconazole will increase the level or effect of silodosin by P-glycoprotein (MDR1) efflux transporter. Contraindicated. Not recommended during and 2 weeks after itraconazole treatment.

            • simvastatin

              itraconazole will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated during and 2 weeks after itraconazole treatment. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure.

            • solifenacin

              itraconazole will increase the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration in patients with renal or hepatic impairment may result in increased solifenacin levels and increased risk for potentially fatal adverse events.

            • ticagrelor

              itraconazole increases levels of ticagrelor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated during and 2 weeks after itraconazole treatment.

            • tolvaptan

              itraconazole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Larger doses of strong CYP3A4 inhibitors may produce larger increases in tolvaptan exposure. Concomitant use of tolvaptan with strong CYP3A4 inhibitors is contraindicated.

            • triazolam

              itraconazole will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Both drugs will increase QT interval

              itraconazole increases levels of triazolam by decreasing metabolism. Contraindicated.

            • ubrogepant

              itraconazole will increase the level or effect of ubrogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • venetoclax

              itraconazole will increase the level or effect of venetoclax by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Use of strong CYP3A4 inhibitors is contraindicated with venetoclax during the initial ramp-up dosing phase. If a strong CYP3A inhibitor must be used after the ramp-up phase, reduce the venetoclax dose by at least 75%.

            • voclosporin

              itraconazole will increase the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            Serious - Use Alternative (173)

            • abametapir

              abametapir will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • acalabrutinib

              itraconazole will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.

            • ado-trastuzumab emtansine

              itraconazole increases levels of ado-trastuzumab emtansine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider an alternate medication with no or minimal potential to inhibit CYP3A4. If concomitant use of strong CYP3A4 inhibitors is unavoidable, consider delaying ado-trastuzumab until the strong CYP3A4 inhibitors have cleared from the circulation (~3 elimination half-lives of the inhibitors) when possible. If a strong CYP3A4 inhibitor is coadministered and ado-trastuzumab cannot be delayed, closely monitor for adverse reactions.

            • afatinib

              itraconazole increases levels of afatinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Reduce afatinib daily dose by 10 mg if not tolerated when coadministered with P-gp inhibitors.

            • aliskiren

              itraconazole will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Consider an alternative with no or minimal potential to inhibit CYP3A4. If concomitant use of strong CYP3A4 inhibitors is unavoidable, closely monitor for respiratory depression and sedation, and consider decreasing alfentanil dose necessary.

            • alitretinoin

              itraconazole will increase the level or effect of alitretinoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • almotriptan

              itraconazole will increase the level or effect of almotriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Start almotriptan dose at 6.25 mg when coadministered with potent CYP3A4 inhibitors. Do not exceed 12.5 mg/day. Avoid concomitant use of almotriptan and potent CYP3A4 inhibitors in patients with renal or hepatic impairment.

            • alprazolam

              itraconazole increases levels of alprazolam by decreasing metabolism. Avoid or Use Alternate Drug.

            • amiodarone

              itraconazole will increase the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              amiodarone and itraconazole both increase QTc interval. Avoid or Use Alternate Drug. Coadministration of amiodarone and a QT prolonging agent may result in additive effects on the QT interval and increase risk of torsades de pointes.

            • apalutamide

              apalutamide will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concurrent use 2 weeks before and during itraconazole treatment. Evaluate for loss of therapeutic effect if medication must be coadministered.

            • aprepitant

              itraconazole will increase the level or effect of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • atorvastatin

              itraconazole will increase the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Limit atorvastatin dose to 20 mg/day

            • avapritinib

              itraconazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

            • axitinib

              itraconazole increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration with strong CYP3A4 inhibitors, reduce axitinib dose by 50%.

            • bazedoxifene/conjugated estrogens

              itraconazole will increase the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • bedaquiline

              itraconazole will increase the level or effect of bedaquiline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of bedaquiline with strong CYP3A4 inhibitors for >14 consecutive days, unless the benefit of treatment outweighs the risk

            • bosutinib

              itraconazole increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.

              itraconazole increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • brigatinib

              itraconazole will increase the level or effect of brigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A inhibitor cannot be avoided, reduce the brigatinib once daily dose by about 50% (ie, from 180 mg to 90 mg, or from 90 mg to 60 mg). After discontinuation of a strong CYP3A inhibitor, resume the brigatinib dose that was tolerated prior to initiating the strong CYP3A inhibitor.

            • bromocriptine

              itraconazole will increase the level or effect of bromocriptine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • budesonide

              itraconazole will increase the level or effect of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is necessary, closely monitor for signs and symptoms of corticosteroid excess.

            • buprenorphine

              itraconazole will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • buprenorphine transdermal

              itraconazole will increase the level or effect of buprenorphine transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • cabazitaxel

              itraconazole will increase the level or effect of cabazitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabazitaxel with strong CYP3A4 inhibitors. If patients require coadministration of a strong CYP3A inhibitor, consider a 25% cabazitaxel dose reduction.

            • cabozantinib

              itraconazole will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.

            • calcitriol

              itraconazole will increase the level or effect of calcitriol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • carbamazepine

              itraconazole will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended 2 weeks before, during, and 2 weeks after itraconazole.

              carbamazepine will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended 2 weeks before, during, and 2 weeks after itraconazole.

            • ceritinib

              itraconazole increases levels of ceritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid if possible; if concomitant use is unavoidable, reduce ceritinib dose by ~33%; after discontinuation of strong CYP3A inhibitor, resume at previous dose.

            • chloroquine

              itraconazole will increase the level or effect of chloroquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • clarithromycin

              itraconazole will increase the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • clobetasone

              itraconazole will increase the level or effect of clobetasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors may increase systemic corticosteroid adverse effects; monitor for signs/symptoms of high corticosteroid concentrations including Cushing type signs/symptoms.

            • clozapine

              itraconazole will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • cobicistat

              itraconazole will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • cobimetinib

              itraconazole will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

            • colchicine

              itraconazole will increase the level or effect of colchicine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid use of colchicine with P-gp inhibitors. If coadministration is necessary, decrease colchicine dose or frequency as recommended in prescribing information. Use of any colchicine product in conjunction with P-gp inhibitors is contraindicated in patients with renal or hepatic impairment.

              itraconazole will increase the level or effect of colchicine by Other (see comment). Avoid or Use Alternate Drug. Colchicine is a P-gp and CYP3A4 substrate. Avoid use with drugs that are both P-gp and strong CYP3A4 inhibitors. If coadministration is necessary, decrease colchicine dose or frequency as recommended in prescribing information. Use of any colchicine product in conjunction with strong CYP3A4 inhibitors is contraindicated in patients with renal or hepatic impairment.

            • conjugated estrogens

              itraconazole will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • conjugated estrogens, vaginal

              itraconazole will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • copanlisib

              itraconazole will increase the level or effect of copanlisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use with strong CYP3A inhibitors cannot be avoided, reduce copanlisib dose to 45 mg.

            • crizotinib

              itraconazole increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If combination cannot be avoided, decrease crizotinib dose to 250 mg daily. Monitor for increased crizotinib toxicities, including QTc interval prolongation and ventricular arrhythmias. .

            • dabrafenib

              itraconazole will increase the level or effect of dabrafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended during and 2 weeks after itraconazole.

            • darifenacin

              itraconazole will increase the level or effect of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended during and 2 weeks after itraconazole.

            • dasatinib

              itraconazole will increase the level or effect of dasatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended during and 2 weeks after itraconazole.

            • dexlansoprazole

              dexlansoprazole will decrease the level or effect of itraconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • docetaxel

              itraconazole will increase the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, consider a 50% docetaxel dose reduction and monitor for increased docetaxel toxicities.

            • doxorubicin

              itraconazole will increase the level or effect of doxorubicin by Other (see comment). Avoid or Use Alternate Drug. Doxorubicin is a CYP3A4 and P-gp substrate. Avoid use in combination with CYP3A4 and P-gp inhibitors due to the potential for increased doxorubicin systemic exposure and effects.

            • edoxaban

              itraconazole will increase the level or effect of edoxaban by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Dose adjustment may be required with strong P-gp inhibitors. DVT/PE treatment: Decrease dose to 30 mg PO once daily. NVAF: No dose reduction recommended

            • efavirenz

              itraconazole will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended 2 weeks before and during itraconazole.

              efavirenz will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended 2 weeks before and during itraconazole.

            • elbasvir/grazoprevir

              itraconazole will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • eletriptan

              itraconazole increases levels of eletriptan by decreasing metabolism. Contraindicated. Use of eletriptan within at least 72 hr of treatment with a strong CYP3A4 inhibitor is contraindicated.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              itraconazole will increase the level or effect of elvitegravir/cobicistat/emtricitabine/tenofovir DF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • encorafenib

              itraconazole will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • entrectinib

              itraconazole will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • enzalutamide

              itraconazole will increase the level or effect of enzalutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              enzalutamide will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erdafitinib

              itraconazole will increase the level or effect of erdafitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration with strong CYP3A4 inhibitors, monitor closely for adverse reactions and consider decreasing dose accordingly. If strong CYP3A4 inhibitor is discontinued, consider increasing erdafitinib dose in the absence of any drug-related toxicities.

            • erlotinib

              itraconazole will increase the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. When combination must be used, closely monitor for severe adverse reactions (eg, severe diarrhea, severe skin reactions). If severe adverse reactions do occur, reduce erlotinib dose (in 50 mg decrements).

            • erythromycin base

              itraconazole will increase the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin ethylsuccinate

              itraconazole will increase the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

              itraconazole will increase the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin stearate

              itraconazole will increase the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • esomeprazole

              esomeprazole will decrease the level or effect of itraconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • eszopiclone

              itraconazole will increase the level or effect of eszopiclone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • everolimus

              itraconazole will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended during and 2 weeks after itraconazole.

              itraconazole will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Not recommended during and 2 weeks after itraconazole.

            • famotidine

              famotidine will decrease the level or effect of itraconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • fedratinib

              itraconazole will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

            • felbamate

              itraconazole will increase the level or effect of felbamate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • fentanyl

              itraconazole will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended during and 2 weeks after itraconazole. If coadministration with fentanyl is necessary, closely monitor for respiratory depression and sedation and consider fentanyl dose adjustments until stable drug effects are achieved.

            • fentanyl intranasal

              itraconazole will increase the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended during and 2 weeks after itraconazole. If coadministration with fentanyl is necessary, closely monitor for respiratory depression and sedation and consider fentanyl dose adjustments until stable drug effects are achieved.

            • fentanyl transdermal

              itraconazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended during and 2 weeks after itraconazole. If coadministration with fentanyl is necessary, closely monitor for respiratory depression and sedation and consider fentanyl dose adjustments until stable drug effects are achieved.

            • fentanyl transmucosal

              itraconazole will increase the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended during and 2 weeks after itraconazole. If coadministration with fentanyl is necessary, closely monitor for respiratory depression and sedation and consider fentanyl dose adjustments until stable drug effects are achieved.

            • fexinidazole

              itraconazole will decrease the level or effect of fexinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration, monitor fexinidazole for decreased efficacy owing to decreased plasma concentrations of active M1 and M2 metabolites.

              fexinidazole and itraconazole both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.

            • fluconazole

              fluconazole and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • fluticasone intranasal

              itraconazole will increase the level or effect of fluticasone intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors may increase systemic corticosteroid adverse effects; monitor for signs/symptoms of high corticosteroid concentrations including Cushing type signs/symptoms.

            • fosamprenavir

              itraconazole will increase the level or effect of fosamprenavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Do not exceed itraconazole dose to 200 mg/day in patients receiving fosamprenavir/ritonavir. In patients receiving fosamprenavir alone, dose reductions may be needed for patients receiving itraconazole doses greater than 400 mg/day.

            • gilteritinib

              itraconazole will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects.

            • hydroxyprogesterone caproate

              itraconazole will increase the level or effect of hydroxyprogesterone caproate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ibrutinib

              itraconazole increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. 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), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

            • ibuprofen/famotidine

              ibuprofen/famotidine will decrease the level or effect of itraconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Administer acid neutralizing medicines at least 2 hours before or 2 hours after the intake of itraconazole.

            • idelalisib

              itraconazole will increase the level or effect of idelalisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministered with strong CYP3A inhibitors, monitor for signs of idelalisib toxicity; follow recommendations for dosage modifications if adverse reactions occur

              idelalisib will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • imipramine

              imipramine and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • isosorbide dinitrate

              itraconazole will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • isosorbide mononitrate

              itraconazole will increase the level or effect of isosorbide mononitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ivosidenib

              itraconazole will increase the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of a strong CYP3A4 inhibitor is unavoidable, reduce ivosidenib dose to 250 mg qDay. If the strong inhibitor is discontinued, increase ivosidenib dose (after at least 5 half-lives of the strong CYP3A4 inhibitor) to 500 mg qDay. Monitor for increased risk of QTc interval prolongation.

              ivosidenib will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Do not administer ivosidenib with itraconzole due to expected loss of antifungal efficacy.

            • ketamine

              itraconazole will increase the level or effect of ketamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ketoconazole

              itraconazole will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              ketoconazole will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lansoprazole

              lansoprazole will decrease the level or effect of itraconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • lapatinib

              itraconazole will increase the level or effect of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of strong CYP3A4 inhibitors with lapatinib. If an overlap in therapy cannot be avoided, consider reducing lapatinib dose to 500 mg/day during, and within 1 week of completing treatment with strong CYP3A4 inhibitor.

            • larotrectinib

              itraconazole will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

            • lefamulin

              itraconazole will increase the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lefamulin with strong CYP3A inhibitors.

              lefamulin and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • lemborexant

              itraconazole will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lemborexant with moderate or strong CYP3A inhibitors.

            • lofepramine

              lofepramine and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • lopinavir

              lopinavir will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lorlatinib

              itraconazole will increase the level or effect of lorlatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering lorlatinib with strong CYP3A inhibitors. If unavoidable, reduce lorlatinib dose by 25 mg/day. If strong CYP3A inhibitor discontinued, increase to previous lorlatinib (dose after 3 plasma half-lives of strong CYP3A inhibitor). See monograph for further details.

              lorlatinib will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lurbinectedin

              itraconazole will increase the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • macimorelin

              itraconazole will increase the level or effect of macimorelin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • macitentan

              itraconazole will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • maprotiline

              maprotiline and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • mefloquine

              mefloquine increases toxicity of itraconazole by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.

              itraconazole will increase the level or effect of mefloquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for increased toxicity. Avoid coadministration during and for 15 weeks after discontinuing mefloquine.

            • midazolam intranasal

              itraconazole will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of strong CYP3A4 inhibitors with midazolam intranasal causes higher midazolam systemic exposure, which may prolong sedation.

            • midostaurin

              itraconazole will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.

            • mifepristone

              mifepristone will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • nefazodone

              itraconazole will increase the level or effect of nefazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • neratinib

              itraconazole will increase the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inhibitors.

            • nevirapine

              itraconazole will increase the level or effect of nevirapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • nilotinib

              itraconazole will increase the level or effect of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of a strong CYP3A4 inhibitor is unavoidable, reduce nilotinib to 300 mg qDay in patients with resistant or intolerant Ph+ CML or to 200 mg qDay in patients with newly diagnosed Ph+ CML-CP. If strong inhibitor is discontinued, allow a washout period before adjusting the nilotinib dose to the indicated dose.

              itraconazole and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.

            • nizatidine

              nizatidine will decrease the level or effect of itraconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • nortriptyline

              nortriptyline and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • olaparib

              itraconazole will increase the level or effect of olaparib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A inhibitors cannot be avoided, reduce olaparib dose to 150 mg (capsule) or 100 mg (tablet) PO BID. Do not substitute tablets with capsules.

            • ombitasvir/paritaprevir/ritonavir

              itraconazole will increase the level or effect of ombitasvir/paritaprevir/ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir

              itraconazole will increase the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • omeprazole

              omeprazole will decrease the level or effect of itraconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • palbociclib

              itraconazole will increase the level or effect of palbociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of palbociclib with strong CYP3A inhibitors. If unable to avoid, reduce palbociclib dose to 75 mg/day.

            • pantoprazole

              pantoprazole will decrease the level or effect of itraconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • pemigatinib

              itraconazole will increase the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pemigatinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pemigatinib dose.

            • perphenazine

              perphenazine and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • pexidartinib

              itraconazole will increase the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pexidartinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pexidartinib dose.

            • phenytoin

              phenytoin decreases levels of itraconazole by increasing metabolism. Avoid or Use Alternate Drug.

            • pimavanserin

              itraconazole will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease dose to 10 mg/day if pimavanserin is coadministered with strong CYP3A4 inhibitors.

            • pitolisant

              itraconazole will increase the level or effect of pitolisant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • pralsetinib

              itraconazole will increase the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • prochlorperazine

              prochlorperazine and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • promazine

              promazine and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • promethazine

              promethazine and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • protriptyline

              protriptyline and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • rabeprazole

              rabeprazole will decrease the level or effect of itraconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • red yeast rice

              itraconazole will increase the level or effect of red yeast rice by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. May increase creatine kinase levels and increase risk of myopathy or rhabdomyolysis; red yeast rice contains monocolin K (reportedly identical to lovastatin)

            • regorafenib

              itraconazole will increase the level or effect of regorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increase regorafenib levels and decrease exposure of the active metabolites M-2 and M-5. Not recommended during and 2 weeks after itraconazole treatment.

            • ribociclib

              itraconazole will increase the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If a strong CYP3A inhibitor must be coadministered with ribociclib, reduce the ribociclib starting dose to 400 mg/day.

            • rifabutin

              itraconazole will increase the level or effect of rifabutin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • rimegepant

              itraconazole will increase the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              itraconazole will increase the level or effect of rimegepant by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • riociguat

              itraconazole will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ruxolitinib

              itraconazole will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L

            • Saccharomyces boulardii

              itraconazole decreases effects of Saccharomyces boulardii by unspecified interaction mechanism. Avoid or Use Alternate Drug. Systemic or oral antifungals may decrease activity of probiotic.

            • salmeterol

              itraconazole will increase the level or effect of salmeterol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • saquinavir

              saquinavir will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • selpercatinib

              itraconazole will increase the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • selumetinib

              itraconazole will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.

            • siponimod

              itraconazole will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • sirolimus

              itraconazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended during and 2 weeks after itraconazole treatment.

              itraconazole will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Not recommended during and 2 weeks after itraconazole treatment.

            • sodium bicarbonate

              sodium bicarbonate will decrease the level or effect of itraconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • sodium citrate/citric acid

              sodium citrate/citric acid will decrease the level or effect of itraconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • sonidegib

              itraconazole will increase the level or effect of sonidegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sonidegib with strong CYP3A4 inhibitors.

            • sorafenib

              itraconazole will increase the level or effect of sorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • stiripentol

              itraconazole will increase the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • suvorexant

              itraconazole increases levels of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Suvorexant not recommended with use of strong CYP3A4 inhibitors.

            • tadalafil

              itraconazole will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For ED limit tadalafil to max of 2.5 mg/day (for daily use) or 10 mg dose every 72 hr (for use as needed). Avoid concurrent use of tadalafil for pulmonary HTN in patients taking strong CYP3A4 inhibitors.

            • talazoparib

              itraconazole will increase the level or effect of talazoparib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration with certain P-gp inhibitors (ie, amiodarone, carvedilol, clarithromycin, itraconazole, verapamil) cannot be avoided, reduce talazoparib dose to 0.75 mg qDay. Once P-gp inhibitors are discontinued, increase talazoparib dose (after 3-5 half-lives of the inhibitor) to dose used prior to initiating the P-gp inhibitor(s).

            • tamsulosin

              itraconazole increases levels of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended during and 2 weeks after itraconazole treatment. .

            • tazemetostat

              itraconazole will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of tazemetostat with strong CYP3A4 inhibitors.

            • temsirolimus

              itraconazole will increase the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • teniposide

              itraconazole will increase the level or effect of teniposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tepotinib

              itraconazole will increase the level or effect of tepotinib by Other (see comment). Avoid or Use Alternate Drug. Interaction not studied clinically. Metabolism and data suggest drugs that are strong CYP3A4 and P-gp inhibitors may increase tepotinib (a P-gp and CYP3A4 substrate) effects and risk of toxicities.

            • thioridazine

              thioridazine and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • tiagabine

              itraconazole will increase the level or effect of tiagabine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tipranavir

              tipranavir will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tofacitinib

              itraconazole increases levels of tofacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce tofacitinib dose to 5 mg qDay when coadministered with potent CYP3A4 inhibitors.

            • tolterodine

              itraconazole will increase the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • topotecan

              itraconazole will increase the level or effect of topotecan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Product labeling for PO topotecan recommends avoiding concomitant use of P-gp inhibitors; the interaction with IV topotecan may be less severe but is still likely of clinical significance

            • trabectedin

              itraconazole will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

            • trazodone

              itraconazole will increase the level or effect of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              trazodone and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • triamcinolone acetonide injectable suspension

              itraconazole will increase the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • trifluoperazine

              trifluoperazine and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • trimipramine

              trimipramine and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • tucatinib

              tucatinib will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • vandetanib

              itraconazole will increase the level or effect of vandetanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • vardenafil

              itraconazole will increase the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              itraconazole increases levels of vardenafil by decreasing metabolism. Contraindicated. Greater risk in pts. over 75 yrs old.

            • vemurafenib

              itraconazole increases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • verapamil

              itraconazole will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Observe the patient for development of toxicity associated with verapamil (peripheral edema, dizziness, hypotension, flushing, headache). Consider reducing the dose of verapamil or withdrawing one of the agents.

            • vilazodone

              itraconazole increases levels of vilazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors may increase vilazodone plasma levels by 50% - Reduce daily dose to 20 mg.

            • vorapaxar

              itraconazole increases levels of vorapaxar by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • voriconazole

              itraconazole will increase the level or effect of voriconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • voxelotor

              itraconazole will increase the level or effect of voxelotor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor is primarily metabolized by CYP3A4. Avoid coadministration with strong CYP3A4 inhibitors. If unable to avoid coadministration, reduce voxelotor dose (see Dosage Modifications).

              voxelotor will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            • warfarin

              itraconazole will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              itraconazole increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • ziprasidone

              itraconazole and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.

            Monitor Closely (253)

            • abemaciclib

              itraconazole will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. In patients with starting doses of 150 or 200 mg BID, reduce abemaciclib dose to 100 mg BID when coadminister with strong CYP3A inhibitors. In patients who reduced dose to 100 mg BID due to adverse reactions, further reduce abemaciclib dose to 50 mg BID when coadministered with strong CYP3A inhibitors. If the strong CYP3A inhibitoris discontinued, increase abemaciclib dose (after 3-5 half-lives of the inhibitor) to the dose that was used before starting the inhibitor.

            • alfentanil

              itraconazole will increase the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • alosetron

              itraconazole will increase the level or effect of alosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • aluminum hydroxide

              aluminum hydroxide will decrease the level or effect of itraconazole by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Administer acid neutralizing medicines at least 2 hours before or 2 hours after itraconazole.

            • amitriptyline

              itraconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • amlodipine

              itraconazole will increase the level or effect of amlodipine by Other (see comment). Modify Therapy/Monitor Closely. CCBs elicit negative inotropic effects which may be additive to those of itraconazole; additionally, itraconazole can inhibit the metabolism of calcium channel blockers. Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

            • apalutamide

              itraconazole will increase the level or effect of apalutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of apalutamide with strong CYP3A4 or CYP2C8 inhibitors does not require initial dosage modification; however, dose reduction may be needed based on tolerability.

            • apixaban

              itraconazole will increase the level or effect of apixaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Apixaban is a both CYP3A4 and P-gp substrate. For patients receiving apixaban 5 or 10 mg BID, decrease apixaban dose by 50% when coadministered with drugs that are both P-gp and strong CYP3A4 inhibitors. For patients receiving apixaban 5 mg BID, avoid coadministration with combined P-gp and strong CYP3A4 inhibitors.

            • aripiprazole

              itraconazole will increase the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. For aripiprazole oral formulations other than the extended-release injectable: Reduce aripiprazole dose by 50% of the usual dose when initiating concomitant therapy with a strong CYP3A4 inhibitor, and further to 25% of the usual dose in patients who are also receiving strong CYP2D6 inhibitors (e.g., paroxetine, quinidine) or who are CYP2D6 poor metabolizers. Consider reducing apixaban dose to up to 75% when combining a strong CYP3A4 inhibitor with a less potent CYP2D6 inhibitor. For extended-release injectable aripiprazole: Please refer to prescribing information.

            • armodafinil

              itraconazole will increase the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • arsenic trioxide

              arsenic trioxide and itraconazole both increase QTc interval. Use Caution/Monitor.

            • artemether/lumefantrine

              artemether/lumefantrine will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              itraconazole and artemether/lumefantrine both increase QTc interval. Use Caution/Monitor.

            • atazanavir

              itraconazole will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • atevirdine

              itraconazole increases levels of atevirdine by decreasing metabolism. Use Caution/Monitor.

            • azithromycin

              azithromycin and itraconazole both increase QTc interval. Use Caution/Monitor.

            • bazedoxifene/conjugated estrogens

              itraconazole will increase the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • benzhydrocodone/acetaminophen

              itraconazole will increase the level or effect of benzhydrocodone/acetaminophen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors may increase hydrocodone (benzhydrocodone is prodrug of hydrocodone) plasma concentrations and can result in potentially fatal respiratory depression.

            • berotralstat

              itraconazole increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • betrixaban

              itraconazole increases levels of betrixaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Decrease betrixaban dose to 80 mg PO once, then 40 mg PO qDay if coadministered with a P-gp inhibitor.

            • bexarotene

              itraconazole will increase the level or effect of bexarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • bortezomib

              itraconazole will increase the level or effect of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • bosentan

              itraconazole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              bosentan will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • brentuximab vedotin

              itraconazole increases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor patients for adverse reactions. .

            • brexpiprazole

              itraconazole will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

            • buprenorphine subdermal implant

              itraconazole will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

            • buprenorphine, long-acting injection

              itraconazole will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • buspirone

              itraconazole will increase the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit buspirone dose 2.5 mg/da. Monitor for increased buspirone effects/toxicities when combined with strong CYP3A4 inhibitors.

            • busulfan

              itraconazole increases levels of busulfan by decreasing hepatic clearance. Use Caution/Monitor.

              itraconazole will increase the level or effect of busulfan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • calcifediol

              itraconazole will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Closely monitor when initiating or discontinuing a strong CYP3A4 inhibitor.

            • calcium carbonate

              calcium carbonate will decrease the level or effect of itraconazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Administer acid neutralizing medicines at least 2 hours before or 2 hours after itraconazole.

            • cannabidiol

              itraconazole will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

            • capmatinib

              itraconazole will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cariprazine

              itraconazole will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • cenobamate

              cenobamate will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • cevimeline

              itraconazole will increase the level or effect of cevimeline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • chlordiazepoxide

              itraconazole will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • chlorpromazine

              chlorpromazine and itraconazole both increase QTc interval. Use Caution/Monitor.

            • chlorpropamide

              itraconazole will decrease the level or effect of chlorpropamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ciclesonide inhaled

              itraconazole will increase the level or effect of ciclesonide inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cilostazol

              itraconazole will increase the level or effect of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider a dose reduction to 50 mg BID in patient who are concurrenlt receiving strong CYP3A4 inhibitors.

            • cimetidine

              cimetidine will decrease the level or effect of itraconazole by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Administer acid neutralizing medicines at least 2 hours before or 2 hours after itraconazole. When taking with cimetidine, administer with non-diet cola to increase GI acidity.

            • cinacalcet

              itraconazole will increase the level or effect of cinacalcet by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • citalopram

              itraconazole increases levels of citalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • clarithromycin

              clarithromycin will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              clarithromycin and itraconazole both increase QTc interval. Use Caution/Monitor.

            • clevidipine

              itraconazole will increase the level or effect of clevidipine by Other (see comment). Modify Therapy/Monitor Closely. CCBs elicit negative inotropic effects which may be additive to those of itraconazole; additionally, itraconazole can inhibit the metabolism of calcium channel blockers. Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

            • clonazepam

              itraconazole will increase the level or effect of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • clorazepate

              itraconazole will increase the level or effect of clorazepate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cobicistat

              cobicistat, itraconazole. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Specific dosage recommendations for itraconazole are not available when coadministered with cobicistat.

            • cortisone

              itraconazole will increase the level or effect of cortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • cyclosporine

              itraconazole will increase the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dabigatran

              itraconazole will increase the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Atrial fibrillation: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <30 mL/min. DVT/PE treatment: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <50 mL/min

            • darolutamide

              itraconazole will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.

            • darunavir

              itraconazole, darunavir. Either increases effects of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. When coadministration of itraconazole with darunavir/ritonavir is required, itraconazole should not exceed 200 mg/day.

            • daunorubicin

              itraconazole will increase the level or effect of daunorubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • deferasirox

              deferasirox will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • deflazacort

              itraconazole will increase the level or effect of deflazacort by Other (see comment). Modify Therapy/Monitor Closely. Itraconazole is a strong P-gp and CYP3A4 inhibitor.Decrease deflazacort (P-gp and CYP3A4 substrate) dose to one-third of the recommended dose if coadministered with strong CYP3A4 and/or P-gp inhibitors.

            • dexamethasone

              itraconazole will increase the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              dexamethasone will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • diazepam

              itraconazole will increase the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • diazepam intranasal

              itraconazole will increase the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

            • didanosine

              didanosine will decrease the level or effect of itraconazole by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Applies to didanosine chewable tablets and powder for oral solution; administer 2 hr before or several hours after didanosine oral solution or chewable tablet administration

            • dienogest/estradiol valerate

              itraconazole will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • digoxin

              itraconazole will increase the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Measure digoxin levels before initiating concomitant drugs. Monitor and consider reducing the digoxin dose by ~30-50% or modifying the dosing frequency.

            • diltiazem

              diltiazem will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of diltiazem and itraconazole may increase both drug levels, toxities, and additive negative inotropic effects.

              itraconazole will increase the level or effect of diltiazem by Other (see comment). Modify Therapy/Monitor Closely. CCBs elicit negative inotropic effects which may be additive to those of itraconazole; additionally, itraconazole can inhibit the metabolism of calcium channel blockers. Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

            • dolasetron

              dolasetron and itraconazole both increase QTc interval. Use Caution/Monitor.

            • doravirine

              itraconazole will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • doxepin cream

              itraconazole will increase the level or effect of doxepin cream by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • doxorubicin liposomal

              itraconazole will increase the level or effect of doxorubicin liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              itraconazole will increase the level or effect of doxorubicin liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • dronabinol

              itraconazole will increase the level or effect of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dutasteride

              itraconazole will increase the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • duvelisib

              itraconazole will increase the level or effect of duvelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with a strong CYP3A4 inhibitor increases duvelisib AUC, which may increase the risk of duvelisib toxicities. Reduce duvelisib dose to 15 mg BID when coadministered with a strong CYP3A4 inhibitor.

              duvelisib will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce duvelisib dose to 15 mg BID when coadministered with a strong CYP3A4 inhibitor.

            • elagolix

              itraconazole will increase the level or effect of elagolix by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of elagolix 200 mg BID with strong CYP3A inhibitors for >1 month is not recommended. Limit elagolix dose to 150 mg qDay and CYP3A inhibitor duration of use to 6 months if coadministered.

              elagolix decreases levels of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • eluxadoline

              itraconazole increases levels of eluxadoline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. As a precautionary measure due to incomplete information on the metabolism of eluxadoline, use caution when coadministered with strong CYP3A4 inhibitors.

            • elvitegravir

              itraconazole increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. When coadministered with elvitegravir, limit dose of itraconazole should not exceed 200 mg/day.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF, itraconazole. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat and itraconazole are CYP3A4 inhibitors; do not exceed itraconazole dose of 200 mg/day.

            • enfortumab vedotin

              itraconazole increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

            • erythromycin base

              erythromycin base will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              erythromycin base will increase the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              erythromycin ethylsuccinate will increase the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              erythromycin lactobionate will increase the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              erythromycin stearate will increase the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • escitalopram

              itraconazole will increase the level or effect of escitalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estradiol

              itraconazole will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              itraconazole will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • estradiol vaginal

              itraconazole will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.

            • estrogens conjugated synthetic

              itraconazole will increase the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estrogens esterified

              itraconazole will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estropipate

              itraconazole will increase the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ethinylestradiol

              itraconazole will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inhibitors such as itraconazole may increase plasma hormone levels.

            • ethosuximide

              itraconazole will increase the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • etonogestrel

              itraconazole will increase the level or effect of etonogestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • etoposide

              itraconazole will increase the level or effect of etoposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • etravirine

              itraconazole will increase the level or effect of etravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Dose adjustments for itraconazole, ketoconazole or posaconazole may be necessary depending on the other coadministered drugs.

            • fedratinib

              fedratinib will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • finasteride

              itraconazole will increase the level or effect of finasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • flecainide

              flecainide and itraconazole both increase QTc interval. Modify Therapy/Monitor Closely.

            • fludrocortisone

              itraconazole will increase the level or effect of fludrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • flunisolide inhaled

              itraconazole will increase the level or effect of flunisolide inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • flurazepam

              itraconazole will increase the level or effect of flurazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fluticasone furoate inhaled

              itraconazole will increase the level or effect of fluticasone furoate inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inhibitors may increase fluticasone systemic exposure

            • fluticasone inhaled

              itraconazole will increase the level or effect of fluticasone inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inhibitors may increase fluticasone systemic exposure

            • fostamatinib

              itraconazole will increase the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inhibitors may increase exposure to R406 (fostamatinib major active metabolite). Monitor for toxicities that may require fostamatinib dose reduction.

            • fostemsavir

              itraconazole and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

            • gefitinib

              itraconazole increases levels of gefitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of strong CYP3A4 inhibitors may increase risk for gefitinib adverse effects.

            • glasdegib

              itraconazole will increase the level or effect of glasdegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider alternate therapies that are not strong CYP3A inhibitors or monitor for increased risk of adverse effects, including QTc interval prolongation.

            • glecaprevir/pibrentasvir

              itraconazole will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              itraconazole will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • guanfacine

              itraconazole will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. For extended-release (ER) guanfacine, if coadministered, decrease the guanfacine dosage to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available.

            • haloperidol

              haloperidol and itraconazole both increase QTc interval. Modify Therapy/Monitor Closely.

              itraconazole will increase the level or effect of haloperidol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ibutilide

              ibutilide and itraconazole both increase QTc interval. Use Caution/Monitor.

            • ifosfamide

              itraconazole will decrease the level or effect of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of CYP3A4 inhibitors may decrease the metabolism of ifosfamide to its active alkylating metabolites and decrease the efficacy of ifosfamide.

            • iloperidone

              itraconazole will increase the level or effect of iloperidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce iloperidone dose by 50% when administered with a strong CYP3A4 inhibitor.

            • imatinib

              itraconazole will increase the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • indinavir

              itraconazole will increase the level or effect of indinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce indinavir dose to 600 mg q8hr is recommended when coadministered itraconazole.

            • isoniazid

              isoniazid decreases levels of itraconazole by unspecified interaction mechanism. Use Caution/Monitor.

            • isradipine

              itraconazole will increase the level or effect of isradipine by Other (see comment). Modify Therapy/Monitor Closely. Calcium channel blockers (CCBs) may potentiate negative inotropic effects of itraconazole; additionally, itraconazole can inhibit the metabolism of CCB. Monitor for adverse reactions and consider dose reduction of CCBs.

            • istradefylline

              itraconazole will increase the level or effect of istradefylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed istradefylline 20 mg/day if coadministered with strong CYP3A4 inhibitors.

              istradefylline will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • ivacaftor

              itraconazole will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • ivermectin

              itraconazole will increase the level or effect of ivermectin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ketoconazole

              ketoconazole will increase the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • lacosamide

              itraconazole increases levels of lacosamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider decreasing lacosamide dose when coadministered with strong CYP3A4 inhibitors.

            • lansoprazole

              itraconazole will increase the level or effect of lansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Separate proton pump inhibitors at least 2 hr before or 2 hr after itraconazole. Use of Sporanox oral solution (instead of the capsule) or administration of itraconazole with an acidic beverage (eg, cola) may minimize the significance of this interaction. Closely monitor for reduced itraconazole efficacy if combined.

            • levamlodipine

              itraconazole will increase the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate and strong CYP3A inhibitors results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A inhibitors to determine the need for dose adjustment.

            • levomilnacipran

              itraconazole will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

              itraconazole will increase the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase the plasma hormone concentrations. Use of a nonhormonal contraceptive is recommended.

            • linagliptin

              itraconazole will increase the level or effect of linagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lopinavir

              itraconazole will increase the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit adult maximum itraconazole dose to 200 mg/day in patients receiving lopinavir/ritonavir.

            • loratadine

              itraconazole will increase the level or effect of loratadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              loratadine will increase the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • losartan

              itraconazole decreases effects of losartan by decreasing metabolism. Use Caution/Monitor. May inhibit the conversion of losartan to its active metabolite E-3174. Importance of interaction not established; monitor individual therapeutic response to determine losartan dosage.

            • lumacaftor/ivacaftor

              itraconazole increases levels of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A inhibitors do not impact lumacaftor exposure, but increased ivacaftor exposure by 4.3-fold. Due to the induction effect of lumacaftor on CYP3A, at steady-state the net exposure of ivacaftor is not expected to exceed that when given in the absence of lumacaftor at a dose of 150 mg q12hr (the approved dose of ivacaftor monotherapy). Therefore, no dose adjustment is necessary when CYP3A inhibitors are initiated in patients currently taking lumacaftor/ivacaftor. However, when initiating lumacaftor/ivacaftor in patients taking strong CYP3A inhibitors, reduce the dose to 1 tablet daily (lumacaftor 200 mg/ivacaftor 125 mg total daily dose) for the first week of treatment to allow for the steady-state induction effect of lumacaftor. Following this period, continue with the recommended daily dose. No dose adjustment is required for moderate or weak CYP3A4 inhibitors.

            • lumefantrine

              itraconazole will increase the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              itraconazole and lumefantrine both increase QTc interval. Modify Therapy/Monitor Closely.

            • maraviroc

              itraconazole will increase the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease maraviroc dose to 150 mg BID when coadministered with strong CYP3A4 inhibitors. Maraviroc is contraindicated in patients with severe renal impairment (CrCl <30 mL/min) receiving a strong CYP3A4 inhibitor.

              itraconazole will increase the level or effect of maraviroc by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

            • marijuana

              itraconazole will increase the level or effect of marijuana by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • medroxyprogesterone

              itraconazole will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mestranol

              itraconazole will increase the level or effect of mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • methylprednisolone

              itraconazole will increase the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • mifepristone

              itraconazole, mifepristone. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Do not exceed mifepristone 300 mg/day for Cushing syndrome when coadministered with strong CYP3A4 inhibitors. Monitor for increased concentrations/toxic effects, during and 2 weeks following treatment with mifepristone.

            • mipomersen

              mipomersen, itraconazole. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

            • mirtazapine

              itraconazole will increase the level or effect of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mitotane

              mitotane decreases levels of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

            • modafinil

              itraconazole will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mometasone inhaled

              itraconazole will increase the level or effect of mometasone inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increases risk for systemic corticosteroid side effects

            • mometasone, intranasal

              itraconazole will increase the level or effect of mometasone, intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • montelukast

              itraconazole will increase the level or effect of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • naldemedine

              itraconazole increases levels of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with strong or moderate CYP3A4 inhibitors.

              itraconazole increases levels of naldemedine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with P-gp inhibitors.

            • nefazodone

              nefazodone will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              nefazodone will increase the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nelfinavir

              itraconazole will increase the level or effect of nelfinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              itraconazole will increase the level or effect of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

            • netupitant/palonosetron

              itraconazole will increase the level or effect of netupitant/palonosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Netupitant is mainly metabolized by CYP3A4; no dosage adjustment is required

            • nicardipine

              itraconazole will increase the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              nicardipine will increase the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              itraconazole will increase the level or effect of nicardipine by Other (see comment). Modify Therapy/Monitor Closely. CCBs elicit negative inotropic effects which may be additive to those of itraconazole; additionally, itraconazole can inhibit the metabolism of calcium channel blockers. Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

            • nifedipine

              itraconazole will increase the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider initiating nifedipine at the lowest dose available if given concomitantly with this medication

              nifedipine will decrease the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              itraconazole will increase the level or effect of nifedipine by Other (see comment). Modify Therapy/Monitor Closely. CCBs elicit negative inotropic effects which may be additive to those of itraconazole; additionally, itraconazole can inhibit the metabolism of calcium channel blockers. Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

            • nimodipine

              itraconazole will increase the level or effect of nimodipine by Other (see comment). Modify Therapy/Monitor Closely. CCBs elicit negative inotropic effects which may be additive to those of itraconazole; additionally, itraconazole can inhibit the metabolism of calcium channel blockers. Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

            • nintedanib

              itraconazole increases levels of nintedanib by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. If nintedanib adverse effects occur, management may require interruption, dose reduction, or discontinuation of therapy .

            • nitrendipine

              itraconazole will increase the level or effect of nitrendipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ofloxacin

              itraconazole and ofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

            • oliceridine

              itraconazole will increase the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

            • omeprazole

              itraconazole will increase the level or effect of omeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ondansetron

              itraconazole will increase the level or effect of ondansetron by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. P-gp inhibitors may decrease clearance of ondansetron. No dosage adjustment for ondansetron is recommended

            • osilodrostat

              itraconazole will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

              osilodrostat and itraconazole both increase QTc interval. Use Caution/Monitor.

            • osimertinib

              itraconazole will increase the level or effect of osimertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • ospemifene

              itraconazole increases levels of ospemifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • oxybutynin

              itraconazole will increase the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • oxycodone

              itraconazole increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Oxycodone dose reduction may be warranted when coadministered with strong CYP3A4 inhibitors.

            • paclitaxel

              itraconazole will increase the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • paclitaxel protein bound

              itraconazole will increase the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • paliperidone

              itraconazole and paliperidone both increase QTc interval. Modify Therapy/Monitor Closely.

              itraconazole will increase the level or effect of paliperidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • panobinostat

              itraconazole increases levels of panobinostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce panobinostat starting dose to 10 mg if coadministered with strong CYP3A4 inhibitors.

            • pantoprazole

              itraconazole will increase the level or effect of pantoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. For patients using the Sporanox brand of itraconazole (capsules or solution), administer proton pump inhibitors at least 2 hr before or 2 hr after itraconazole. Use of Sporanox oral solution or administration of itraconazole with an acidic beverage (eg, cola) may minimize the significance of this interaction.

            • parecoxib

              itraconazole will increase the level or effect of parecoxib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • paricalcitol

              itraconazole will increase the level or effect of paricalcitol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • paroxetine

              itraconazole and paroxetine both increase QTc interval. Modify Therapy/Monitor Closely.

            • perampanel

              itraconazole will increase the level or effect of perampanel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • phenobarbital

              phenobarbital will decrease the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • phenytoin

              phenytoin will decrease the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Antifungal failure may occur due to clinically significant decreases in itraconazole serum concentrations when given with phenytoin. Increased itraconazole dosage may be needed.

            • polatuzumab vedotin

              itraconazole will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

            • ponatinib

              itraconazole increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease ponatinib starting dose to 30 mg qDay if concomitantly used with strong CYP3A4 inhibitors.

            • posaconazole

              itraconazole will increase the level or effect of posaconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              itraconazole and posaconazole both increase QTc interval. Use Caution/Monitor.

            • praziquantel

              itraconazole will increase the level or effect of praziquantel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • prednisolone

              itraconazole will increase the level or effect of prednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • prednisone

              itraconazole will increase the level or effect of prednisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • primaquine

              itraconazole will increase the level or effect of primaquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • procainamide

              itraconazole and procainamide both increase QTc interval. Use Caution/Monitor.

            • progesterone intravaginal gel

              itraconazole will increase the level or effect of progesterone intravaginal gel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • progesterone micronized

              itraconazole will increase the level or effect of progesterone micronized by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • progesterone, natural

              itraconazole will increase the level or effect of progesterone, natural by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • propafenone

              itraconazole will increase the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Closely monitor for evidence of propafenone toxicity when used together with a strong CYP3A4 inhibitor. Avoid concurrent use of a CYP2D6 inhibitor in patients receiving proprafenone and a CYP3A4 inhibitor.

            • quazepam

              itraconazole will increase the level or effect of quazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • quercetin

              quercetin will decrease the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • quetiapine

              itraconazole will increase the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

            • quinine

              itraconazole will increase the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rabeprazole

              itraconazole will increase the level or effect of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. For patients using the Sporanox brand of itraconazole (capsules or solution), administer proton pump inhibitors at least 2 hr before or 2 hr after itraconazole. Use of Sporanox oral solution or administration of itraconazole with an acidic beverage (eg, cola) may minimize the significance of this interaction.

            • ramelteon

              itraconazole will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • repaglinide

              itraconazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ribociclib

              ribociclib will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • rifabutin

              rifabutin will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              rifabutin decreases levels of itraconazole by increasing metabolism. Use Caution/Monitor.

              itraconazole increases levels of rifabutin by decreasing metabolism. Modify Therapy/Monitor Closely.

            • rifampin

              rifampin will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              rifampin will decrease the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • rifaximin

              itraconazole increases levels of rifaximin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • rilpivirine

              itraconazole increases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No rilpivirine dose adjustment is required. Clinically monitor for breakthrough fungal infections when azole antifungals are co-administered with rilpivirine.

            • riociguat

              itraconazole will increase the level or effect of riociguat by decreasing metabolism. Modify Therapy/Monitor Closely. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed

              itraconazole will increase the level or effect of riociguat by Other (see comment). Modify Therapy/Monitor Closely. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed

            • ripretinib

              itraconazole will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.

            • risperidone

              itraconazole will increase the level or effect of risperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              itraconazole and risperidone both increase QTc interval. Use Caution/Monitor.

            • ritonavir

              ritonavir will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit itraconazole dose to 200 mg/day in patients receiving ritonavir.

            • rivaroxaban

              itraconazole increases levels of rivaroxaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid concomitant use of rivaroxaban and combined Pgp and strong CYP3A4 inhibitors. Combination may lead to significant increases in rivaroxaban levels and increase bleeding risk.

            • roflumilast

              itraconazole will increase the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • romidepsin

              itraconazole will increase the level or effect of romidepsin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor for toxicity related to increased romidepsin exposure and follow the dose modifications for toxicity when romidepsin is initially coadministered with strong CYP3A4 inhibitor.

              itraconazole and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely.

            • rucaparib

              rucaparib will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • saquinavir

              itraconazole will increase the level or effect of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit itraconazole dose to 200 mg/day in patients receiving saquinavir/ritonavir.

              itraconazole will increase the level or effect of saquinavir by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Limit itraconazole dose to 200 mg/day in patients receiving saquinavir/ritonavir.

            • saxagliptin

              itraconazole will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

            • sildenafil

              itraconazole will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Not recommended during and 2 weeks after itraconazole treatment when sildenafil is used for pulmonary arterial hypertension.

            • simvastatin

              simvastatin will increase the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • sodium bicarbonate

              sodium bicarbonate decreases levels of itraconazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

            • sodium citrate/citric acid

              sodium citrate/citric acid decreases levels of itraconazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

            • sodium zirconium cyclosilicate

              sodium zirconium cyclosilicate will decrease the level or effect of itraconazole by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Check specific recommendations for drugs that exhibit pH-dependent solubility that may affect their systemic exposure and efficacy. In general, administer drugs at least 2 hr before or after sodium zirconium cyclosilicate.

            • sofosbuvir/velpatasvir

              itraconazole will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • sotalol

              itraconazole and sotalol both increase QTc interval. Modify Therapy/Monitor Closely.

            • St John's Wort

              St John's Wort will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              St John's Wort will decrease the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • stiripentol

              stiripentol, itraconazole. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

            • sufentanil

              itraconazole will increase the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • sufentanil SL

              itraconazole will increase the level or effect of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of sufentanil SL with any CYP3A4 inhibitor may increase sufentanil plasma concentration, and, thereby increase or prolonged adverse effects, including potentially fatal respiratory depression.

            • sulfamethoxazole

              sulfamethoxazole and itraconazole both increase QTc interval. Modify Therapy/Monitor Closely.

            • tacrolimus ointment

              itraconazole will increase the level or effect of tacrolimus ointment by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tamoxifen

              itraconazole will increase the level or effect of tamoxifen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP3A4 inhibition decreases metabolism of tamoxifen to N-desmethyl tamoxifen (active metabolite with similar biologic activity)

            • tasimelteon

              itraconazole will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tazemetostat

              tazemetostat will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              tecovirimat will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • teniposide

              itraconazole will increase the level or effect of teniposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • terbinafine

              itraconazole will increase the level or effect of terbinafine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tezacaftor

              itraconazole will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

            • theophylline

              itraconazole will increase the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • tipranavir

              itraconazole will increase the level or effect of tipranavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit itraconazole adult maximum dose to 200 mg/day in patients treated with tipranavir.

            • tobramycin inhaled

              tobramycin inhaled and itraconazole both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Avoid concurrent or sequential use to decrease risk for ototoxicity

            • tolvaptan

              tolvaptan will increase the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • toremifene

              itraconazole increases levels of toremifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Metabolism of toremifene may be inhibited by drugs known to inhibit CYP3A4 hepatic enzymes.

            • tramadol

              itraconazole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • trazodone

              trazodone will decrease the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • trimethoprim

              itraconazole and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

            • trimipramine

              itraconazole will increase the level or effect of trimipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tropisetron

              itraconazole and tropisetron both increase QTc interval. Modify Therapy/Monitor Closely.

            • ulipristal

              itraconazole will increase the level or effect of ulipristal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • umeclidinium bromide/vilanterol inhaled

              itraconazole will increase the level or effect of umeclidinium bromide/vilanterol inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Vilanterol is a CYP3A4 substrate; coadministration with potent CYP3A4 inhibitors may increase systemic exposure

            • upadacitinib

              itraconazole will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.

            • valbenazine

              itraconazole will increase the level or effect of valbenazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce valbenazine dose to 40 mg once daily when coadministered with a strong CYP3A4 inhibitor.

            • velpatasvir

              itraconazole will increase the level or effect of velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • vemurafenib

              itraconazole increases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • venlafaxine

              itraconazole and venlafaxine both increase QTc interval. Modify Therapy/Monitor Closely.

              itraconazole will increase the level or effect of venlafaxine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • verapamil

              verapamil will increase the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              itraconazole will increase the level or effect of verapamil by Other (see comment). Modify Therapy/Monitor Closely. CCBs elicit negative inotropic effects which may be additive to those of itraconazole; additionally, itraconazole can inhibit the metabolism of calcium channel blockers. Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

            • vilanterol/fluticasone furoate inhaled

              itraconazole will increase the level or effect of vilanterol/fluticasone furoate inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Fluticasone furoate and vilanterol are both CYP3A4 substrates; coadministration with potent CYP3A4 inhibitors may increase systemic exposure

            • vinblastine

              itraconazole will increase the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              itraconazole will increase the level or effect of vinblastine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • vincristine

              itraconazole will increase the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              itraconazole will increase the level or effect of vincristine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • vincristine liposomal

              itraconazole will increase the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              itraconazole will increase the level or effect of vincristine liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • vinorelbine

              itraconazole will increase the level or effect of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • voriconazole

              itraconazole and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.

            • voxilaprevir

              itraconazole will increase the level or effect of voxilaprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • zaleplon

              itraconazole will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • zanubrutinib

              itraconazole will increase the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce zanubrutinib dose when coadministered with a strong CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib. See zanubrutinib Dosage Modifications for precise recommendation.

            • ziprasidone

              itraconazole will increase the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • zolpidem

              itraconazole will increase the level or effect of zolpidem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • zonisamide

              itraconazole will increase the level or effect of zonisamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            Minor (44)

            • alvimopan

              itraconazole will increase the level or effect of alvimopan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • ambrisentan

              itraconazole will increase the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • amitriptyline

              itraconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • caffeine

              itraconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

            • clomipramine

              itraconazole will increase the level or effect of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • DHEA, herbal

              DHEA, herbal will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • esomeprazole

              itraconazole will increase the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • fexofenadine

              itraconazole will increase the level or effect of fexofenadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • fluconazole

              fluconazole will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • flucytosine

              flucytosine increases effects of itraconazole by pharmacodynamic synergism. Minor/Significance Unknown.

            • griseofulvin

              griseofulvin will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • indacaterol, inhaled

              itraconazole increases levels of indacaterol, inhaled by Other (see comment). Minor/Significance Unknown. Comment: Data suggests that systemic clearance is influenced by modulation of both P-gp and CYP3A4 activities. No dose adjustment is warranted at the 75 mcg dose.

            • lapatinib

              lapatinib will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • levofloxacin

              itraconazole and levofloxacin both increase QTc interval. Minor/Significance Unknown.

            • loperamide

              itraconazole will increase the level or effect of loperamide by Other (see comment). Minor/Significance Unknown. Monitor ECG when itraconazole is coadministered with loperamide (dose >16mg/day).

            • lumefantrine

              lumefantrine will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • marijuana

              marijuana will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • methylprednisolone

              methylprednisolone will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • metronidazole

              metronidazole will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • miconazole vaginal

              miconazole vaginal will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • modafinil

              modafinil will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • moxifloxacin

              itraconazole and moxifloxacin both increase QTc interval. Minor/Significance Unknown.

            • nafcillin

              nafcillin will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nelfinavir

              nelfinavir will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nevirapine

              nevirapine will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nifedipine

              nifedipine will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nilotinib

              nilotinib will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pentobarbital

              pentobarbital will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              pentobarbital decreases levels of itraconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • phenobarbital

              phenobarbital will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              phenobarbital decreases levels of itraconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • phenytoin

              phenytoin will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pomalidomide

              itraconazole increases levels of pomalidomide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              itraconazole increases levels of pomalidomide by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • posaconazole

              posaconazole will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • prednisone

              prednisone will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • primidone

              primidone will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              primidone decreases levels of itraconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • rifapentine

              rifapentine will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • rufinamide

              rufinamide will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • secobarbital

              secobarbital will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              secobarbital decreases levels of itraconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • topiramate

              topiramate will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • verapamil

              verapamil will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • voriconazole

              voriconazole will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • zafirlukast

              zafirlukast will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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            Adverse Effects

            >10%

            Systemic fungal infections

            • Nausea (11%)

            1-10% (Systemic fungal infections)

            Rash (9%)

            Vomiting (5%)

            Edema (4%)

            Headache (4%)

            Abnormal liver function test results (3%)

            Diarrhea (3%)

            Fever (3%)

            Fatigue (3%)

            Hypertension (3%)

            Pruritus (3%)

            Abdominal pain (2%)

            Dizziness (2%)

            Hypertriglyceridemia (2%)

            Hypokalemia (2%)

            Albuminuria (1%)

            Anorexia (1%)

            Decreased libido (1%)

            Somnolence (1%)

            Anorexia (1%)

            Impotence (1%)

            1-10% (Toenail infections)

            Headache (10%)

            Rhinitis (9%)

            Upper respiratory tract infection (8%)

            Sinusitis, injury (7%)

            Diarrhea (4%)

            Dyspepsia (4%)

            Flatulence (4%)

            Abdominal pain (4%)

            Dizziness (4%)

            Rash (4%)

            Elevated liver enzymes (4%)

            Gastrointestinal disorders (4%)

            Rash (3%)

            Cystitis (3%)

            Urinary tract infection (3%)

            Liver function abnormality (3%)

            Myalgia (3%)

            Nausea (3%)

            Hypertension (2%)

            Appetite increased (2%)

            Constipation (2%)

            Gastritis, gastroenteritis (2%)

            Pharyngitis (2%)

            Abnormal dreaming (2%)

            Orthostatic hypertension (1%)

            Headache (1%)

            Malaise (1%)

            Myalgia (1%)

            Vasculitis (1%)

            Vertigo (1%)

            Frequency Not Defined

            Hepatobiliary disorders: Hyperbilirubinemia

            Cardiac disorders: Cardiac failure, left ventricular failure, tachycardia

            General disorders and administration site conditions: Face edema, chest pain, chills

            Hepatobiliary disorders: Hepatic failure, jaundice

            Investigations: ALT increased, AST increased, blood alkaline phosphatase increased, blood lactate dehydrogenase increased, blood urea increased, gamma glutamyltransferase increased, urine analysis abnormal

            Metabolism and nutrition disorders: Hyperglycemia, hyperkalemia, hypomagnesemia

            Psychiatric disorders: Confusional state

            Renal and urinary disorders: Renal impairment

            Respiratory, thoracic and mediastinal disorders: Dysphonia, cough

            Skin and subcutaneous tissue disorders: Hyperhidrosis

            Vascular disorders: Hypotension

            Postmarketing Reports

            Blood and lymphatic system disorders: Leukopenia, neutropenia, thrombocytopenia

            Immune system disorders: Anaphylaxis; anaphylactic, anaphylactoid and allergic reactions; serum sickness; angioneurotic edema

            Nervous System Disorders: Peripheral neuropathy, paresthesia, hypoesthesia, tremor

            Eye Disorders: Visual disturbances, including vision blurred and diplopia

            Ear and labyrinth disorders: Transient or permanent hearing loss

            Respiratory, thoracic and mediastinal disorders: Pulmonary edema, dyspnea

            Gastrointestinal disorders: Pancreatitis, dysgeusia

            Hepatobiliary disorders: Serious hepatotoxicity (including some cases of fatal acute liver failure), hepatitis

            Skin and subcutaneous tissue disorders: Toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, erythema multiforme, exfoliative dermatitis, leukocytoclastic vasculitis, alopecia, photosensitivity, urticaria

            Musculoskeletal and connective tissue disorders: Arthralgia

            Renal and urinary disorders: Urinary incontinence, pollakiuria

            Reproductive system and breast disorders: Erectile dysfunction

            General disorders and administration site conditions: Peripheral edema

            Investigations: Blood creatine phosphokinase increased

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            Warnings

            Black Box Warnings

            Congestive heart failure

            • Can cause or exacerbate congestive heart failure (CHF)
            • When itraconazole IV was administered to healthy human volunteers and dogs, negative inotropic effects were seen
            • Do not use for the treatment of onychomycosis in patients with ventricular dysfunction (eg, history of CHF)
            • If signs or symptoms of CHF occur during administration, reassess benefit and risk of continuing treatment

            Contraindicated drug interactions

            • Itraconazole is potent CYP4503A4 inhibitor
            • Coadministration of the following drugs are contraindicated with itraconazole: methadone, disopyramide, dofetilide, dronedarone, quinidine, isavuconazole, ergot alkaloids (eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine), irinotecan, ivabradine, lurasidone, oral midazolam, pimozide, triazolam, felodipine, nisoldipine, ranolazine, eplerenone, cisapride, naloxegol, lomitapide, lovastatin, simvastatin, avanafil, ticagrelor
            • In patients with varying degrees of renal or hepatic impairment, coadministration of itraconazole with colchicine, fesoterodine, and solifenacin are contraindicated
            • Coadministration with eliglustat is contraindicated in subjects that are poor or intermediate metabolizers of CYP2D6 and in subjects taking strong or moderate CYP2D6 inhibitors
            • Elevated plasma concentrations of some of these drugs and may increase or prolong both the pharmacologic effects and/or adverse reactions to these drugs (eg, increased plasma concentrations of some of these drugs can lead to QT prolongation and ventricular tachyarrhythmias including occurrences of torsades de pointes)

            Contraindications

            Hypersensitivity

            Contraindicated with certain CYP3A4 substrate drugs (see Black Box Warnings)

            Coadministration with colchicine, fesoterodine, and solifenacin in patients with varying degrees of renal or hepatic impairment

            Coadministration with eliglustat in patients who are poor or intermediated CYP2D6 metabolizers, or if coadministered with strong or moderate CYP2D6 inhibitors

            Increased plasma concentrations resulting from coadministration with itraconazole of some of the aforementioned drugs can lead to QT prolongation and ventricular tachyarrhythmias

            Treatment of onychomycosis in women who are pregnant or plan to become pregnant

            Cautions

            Cases of serious hepatotoxicity, including liver failure and death, reported; discontinue if liver disease develops, and perform liver function tests; readministration discouraged

            Prolongs QT interval; caution with concurrent QT-prolonging drugs or congenital long QT (see Black Box Warnings for drugs contraindicated for use with itraconazole)

            Can cause or exacerbated CHF; not for the treatment of other indications in patients with evidence of ventricular dysfunction unless benefit clearly outweighs risks; risk factors include cardiac disease such as ischemic and valvular disease; significant pulmonary disease such as chronic obstructive pulmonary disease; and renal failure and other edematous disorders; monitor for signs and symptoms of CHF during treatment; if signs or symptoms of CHF appear or worsen during administration, reassess benefit-risk of continuing treatment

            Calcium channel blockers can have negative inotropic effects which may be additive to those of itraconazole. when co-administering itraconazole and calcium channel blockers, monitor carefully for signs and symptoms of CHF during treatment due to an increased risk of CHF

            Life-threatening cardiac arrhythmias and/or sudden death reported when coadministered with drugs that are CYP3A4 substrates and are associated with arrhythmias with increased systemic exposure (eg, pimozide, methadone, quinidine)

            May cause CNS depression, which may impair mental alertness and subsequently impair ability to operate heavy machinery or performing hazardous tasks

            Oral capsule and oral solution are not bioequivalent; do not use interchangeably

            Parenteral form is incompatible with most aqueous solutions; use dedicated line, and do not mix with other drugs in any way

            If peripheral neuropathy occurs that may be attributable to itraconazole, discontinue treatment

            If cystic fibrosis patient does not respond to itraconazole, consider switching to alternative therapy; large differences in itraconazole pharmacokinetic parameters observed in cystic fibrosis patients

            Transient or permanent hearing loss reported in patients receiving treatment with itraconazole; several reports included concurrent administration of quinidine, which is contraindicated; the hearing loss usually resolves when treatment is stopped but can persist in some patients

            Caution with renal impairment; data are limited

            Absorption of itraconazole capsules is reduced when gastric acidity reduced; administer capsules with acidic beverage in patients with reduced gastric acidity and do not administer concomitantly with acid-suppressive therapy; monitor for response

            Only oral solution shown to be effective in oral/esophageal candidiasis; oral solution not recommended in patients at immediate risk for systemic candidiasis

            Itraconazole should not be used to treat voriconazole-refractory aspergillosis; both agents may share resistance mechanisms

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            Pregnancy & Lactation

            Pregnancy

            There are no data on exposure to itraconazole during pregnancy

            Published epidemiologic studies of women exposed to short courses of treatment with itraconazole in the first trimester of pregnancy have reported no risk of major birth defects overall and inconclusive findings on the risk of miscarriage

            Drug should be used for treatment of systemic fungal infections in pregnancy only if benefit outweighs potential risk; therapy should not be administered for treatment of onychomycosis to pregnant patients or to women contemplating pregnancy; drug should not be administered to women of childbearing potential for treatment of onychomycosis unless they are using effective measures to prevent pregnancy and they begin therapy on the second or third day following the onset of menses; highly effective contraception should be continued throughout therapy and for 2 months following the end of treatment

            Animal

            • In animal reproduction studies, itraconazole was found to cause a dose-related increase in maternal toxicity, embryotoxicity, and teratogenicity in rats at dosage levels of approximately (6-25 times the maximum recommended human dose [MRHD] of 390 mg/day based on mg/kg comparisons), and in mice at dosage levels of ~80 mg/kg/day (12 times the MRHD).

            Lactation

            Itraconazole is excreted in human milk

            No data on the amount of itraconazole in human milk, the effects on the breastfed child, or the effects on milk production

            Developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for itraconazole and any potential adverse effects on the breastfed child from itraconazole or from underlying maternal condition

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Triazole antifungal agent; inhibits cytochrome P450-dependent synthesis of ergosterol, which in turn inhibits cell-membrane formation

            Absorption

            AUC: 15.6 hr·mcg/mL (Tolsura 130 mg BID); 14.9 hr·mcg/mL (itraconazole 200 mg BID)

            AUC (Onmel): 2.27 hr·mcg/mL (fasted); 3.34 hr·mcg/mL (fed)

            Trough plasma concentration: 1.2 mcg/mL (Tolsura 130 mg BID); 1 mcg/mL (itraconazole 200 mg BID)

            Peak plasma concentration (steady-state): 1.6 mcg/mL (Tolsura 130 mg BID); 1.5 mcg/mL (itraconazole 200 mg BID)

            Peak plasma concentration (Onmel): 162 ng/mL (fasted); 213 ng/mL (fed)

            Peak plasma time (steady-state): 7 hr (Tolsura 130 mg BID); 5 hr (itraconazole 200 mg BID)

            Peak plasma time (Onmel): 2.9 hr (fasted); 5.7 hr (fed)

            Effect of food

            • Effect of food on the steady-state pharmacokinetics of itraconazole following administration (Tolsura 130 mg BID) for 14.5 days under fed and fasted conditions was evaluated in 20 healthy volunteers
            • A high-fat meal with total caloric content of 919 calories (526 fat calories, 260 carbohydrate calories and 133 protein calories) was used in the study

            Distribution

            Protein bound: 99.8% (albumin); 0.2% (free drug)

            Metabolism

            Extensively metabolized by the liver into a large number of metabolites

            Mainly metabolized by CYP3A4

            Main metabolite is hydroxy-itraconazole, which has in vitro antifungal activity comparable to itraconazole; trough plasma concentrations of this metabolite are about twice those of itraconazole

            Elimination

            Half-life (fasted): 32-42 hr

            Excretion: Urine (35%); feces (54%)

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            Administration

            Oral Administration

            Do not administer with antacids

            Sporanox and generic

            • Capsule and oral solution formulations are not bioequivalent and thus are not interchangeable
            • Generally, oral solution is the preferred formulation because of improved absorption (IDSA [Kauffman 2007])
            • Capsule: Take with food
            • Solution
              • Take on an empty stomach
              • When treating oropharyngeal and esophageal candidiasis, solution should be swished vigorously in mouth (10 mL/dose), then swallowed

            Tolsura

            • Administer with food
            • Swallow whole; do not chew, crush, or break

            Storage

            Sporanox

            • Oral solution: Store ≤25°C (77°F); do not freeze
            • Capsules: Store at 25°C (77°F); excursions permitted 15-30°C (59-86°F)

            Omnel

            • Store at 25°C (77°F); excursions permitted 15-30°C (59-86°F)
            • Dispense in a tight, light resistant container

            Tolsura

            • Store at 25°C (77°F); excursions permitted 15-30°C (59-86°F)
            • Dispense in a tight, light resistant container
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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Sporanox oral
            -
            10 mg/mL solution
            Sporanox oral
            -
            100 mg capsule
            itraconazole oral
            -
            100 mg capsule
            itraconazole oral
            -
            100 mg capsule
            itraconazole oral
            -
            100 mg capsule
            itraconazole oral
            -
            10 mg/mL solution
            itraconazole oral
            -
            100 mg capsule
            itraconazole oral
            -
            100 mg capsule
            itraconazole oral
            -
            100 mg capsule
            itraconazole oral
            -
            100 mg capsule
            itraconazole oral
            -
            100 mg capsule
            itraconazole oral
            -
            100 mg capsule
            itraconazole oral
            -
            10 mg/mL solution
            itraconazole oral
            -
            100 mg capsule
            Sporanox Pulsepak oral
            -
            100 mg capsule
            Tolsura oral
            -
            65 mg capsule

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            itraconazole oral

            ITRACONAZOLE 65 MILLIGRAM CAPSULE - ORAL

            (IT-ra-KON-a-zole)

            COMMON BRAND NAME(S): Tolsura

            WARNING: Itraconazole may rarely cause or worsen heart failure. Tell your doctor right away if you develop symptoms of heart failure, such as shortness of breath, swelling ankles/feet, unusual tiredness, or unusual/sudden unexplained weight gain. Consult your doctor for more details.This medication can slow down the removal of other medications from your body, which may cause very serious (possibly fatal) side effects. Examples of affected drugs include certain "blood thinners" (such as ticagrelor), colchicine, certain drugs to treat irregular heartbeat (such disopyramide, dofetilide, dronedarone, quinidine), eplerenone, ergot alkaloids (such as dihydroergotamine, ergotamine, methylergonovine), felodipine, fesoterodine, irinotecan, ivabradine, lurasidone, methadone, midazolam, nisoldipine, pimozide, ranolazine, certain "statin" cholesterol drugs (such as lovastatin, simvastatin), solifenacin, telithromycin, triazolam, among others. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

            USES: Itraconazole is used to treat a variety of fungal infections. It belongs to a class of drugs known as azole antifungals. It works by stopping the growth of fungi.

            HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start taking itraconazole and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with food as directed by your doctor, usually once or twice daily. Swallow the capsules whole. Do not chew, crush, or break the capsules.The dosage and length of treatment are based on your medical condition, response to treatment, and other medications you may be taking. Take this medication exactly as prescribed by your doctor.For the best effect, take this antifungal at evenly spaced times. To help you remember, take this medication at the same time(s) every day.Continue to take this medication until the full prescribed amount is finished, even if symptoms disappear after a few days. Stopping the medication too early may result in a return of the infection.The capsule, tablet, and solution forms of this medication deliver different amounts of medication and may be used for different purposes. Do not switch between the different forms or brands of this drug without your doctor's direction.Tell your doctor if your condition does not get better or if it gets worse.

            SIDE EFFECTS: See also Warning section.Nausea/vomiting, diarrhea, headache, stomach upset, or dizziness may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: numbness/tingling of arms/legs, hearing loss, mental/mood changes (such as depression).Itraconazole has rarely caused very serious (possibly fatal) liver disease. Tell your doctor right away if you develop symptoms of liver disease, such as: nausea/vomiting that doesn't stop, loss of appetite, stomach/abdominal pain, yellowing eyes/skin, dark urine.Itraconazole can commonly cause a mild rash that is usually not serious. However, you may not be able to tell it apart from a rare rash that could be a sign of a severe allergic reaction. Get medical help right away if you develop any rash.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: See also Warning section.Before taking itraconazole, tell your doctor or pharmacist if you are allergic to it; or to other azole antifungals (such as ketoconazole); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver problems, kidney problems, heart problems (such as heart failure, coronary artery disease, heart valve disease), lung disease (such as chronic obstructive pulmonary disease-COPD).This drug may make you dizzy. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis). Alcohol may also increase the risk of serious liver problems.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Older adults may be at greater risk for hearing loss while using this drug.During pregnancy, this medication should be used only when clearly needed. It may harm an unborn baby. Discuss the risks and benefits with your doctor. Ask about reliable forms of birth control while taking this medication and for 2 months after stopping treatment.Itraconazole passes into breast milk. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Itraconazole interacts with many medications. See also Warning section.Other medications can affect the removal of itraconazole from your body, which may affect how itraconazole works. Examples include efavirenz, isoniazid, nevirapine, rifamycins (such as rifabutin), certain drugs used to treat seizures (such as phenytoin), among others.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

            NOTES: Do not share this medication with others.This medication has been prescribed for your current condition only. Do not use it later for another infection unless your doctor tells you to.Lab and/or medical tests (such as liver function) should be done before you start taking this medication and while you are taking it. Keep all medical and lab appointments. Consult your doctor for more details.

            MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            Information last revised April 2019. Copyright(c) 2021 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

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            • View the formulary and any restrictions for each plan.
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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.