ketoconazole (Rx)

Fungal Infections

Indicated for the treatment of the following systemic fungal infections in patients who have failed or who are intolerant to other therapies: blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis

200-400 mg/day PO

Dosage Modifications

Renal impairment: No dosage modifications provided in manufacturer’s labeling

Hepatic impairment

• No dosage modifications provided in manufacturer’s labeling
• If hepatotoxicity occurs during treatment (ALT levels above UNL or ALT 30% above baseline): Interrupt dosing and order a full set of liver tests

Dosing Considerations

Do not use tablets as first-line treatment; should be used only when other effective antifungal therapy is not available or tolerated and the potential benefits are considered to outweigh the potential of hepatotoxicity

Avoid prescribing tablets to treat skin and nail fungal infections owing to risk of serious liver damage, adrenal gland problems, and harmful interactions with other medicines that outweigh its benefit in treating these conditions, which are not approved uses of the drug (these indications were removed from labeling by the FDA in 2013)

Do not use for fungal meningitis because of poor penetration into the CSF

Cushing Syndrome (Off-label)

Used off-label to inhibit steroidogenesis in patients with Cushing syndrome

600-800 mg/day PO

Used rarely and often toxic at doses required to reduce cortisol secretion

Recurrent Tinea Versicolor (Off-label)

400 mg PO monthly

Fungal Infections

Indicated for the treatment of the following systemic fungal infections in patients who have failed or who are intolerant to other therapies: blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis

<2 years old: Safety and efficacy not established

≥2 years old: 3.3-6.6 mg/kg/day PO  

Dosage Modifications

Renal impairment: No dosage modifications provided in manufacturer’s labeling

Hepatic impairment

• No dosage modifications provided in manufacturer’s labeling
• If hepatotoxicity occurs during treatment (ALT levels above UNL or ALT 30% above baseline): Interrupt dosing and order a full set of liver tests

Dosing Considerations

Do not use tablets as first-line treatment; should be used only when other effective antifungal therapy is not available or tolerated and the potential benefits are considered to outweigh the potential of hepatotoxicity

Avoid prescribing tablets to treat skin and nail fungal infections owing to risk of serious liver damage, adrenal gland problems, and harmful interactions with other medicines that outweigh its benefit in treating these conditions, which are not approved uses of the drug (these indications were removed from labeling by the FDA in 2013)

Do not use for fungal meningitis because of poor penetration into the CSF

Contraindicated (41)

• alfuzosin

  ketoconazole increases levels of alfuzosin by decreasing metabolism. Contraindicated.

• alprazolam

  ketoconazole increases levels of alprazolam by decreasing metabolism. Contraindicated.

• conivaptan

  ketoconazole will increase the level or effect of conivaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of conivaptan with strong CYP3A4 inhibitors is contraindicated.

• dihydroergotamine

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

• dihydroergotamine intranasal

  ketoconazole will increase the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• disopyramide

  ketoconazole will increase the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  disopyramide and ketoconazole both increase QTc interval. Contraindicated.

• dronedarone

  ketoconazole will increase the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  dronedarone and ketoconazole both increase QTc interval. Contraindicated.

• eliglustat

  ketoconazole 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
  
  ketoconazole increases levels of eliglustat by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated. If coadministered with strong or moderate CYP2D6 inhibitors, reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive and intermediate metabolizers; eliglustat is contraindiated if strong or moderate CYP2D6 inhibitors are given concomitantly with strong or moderate CYP3A inhibitors.

• ergoloid mesylates

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

• ergonovine

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

• ergotamine

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

• finerenone

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

• flibanserin

  ketoconazole 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.

• ibutilide

  ibutilide and ketoconazole both increase QTc interval. Contraindicated.

• indapamide

  indapamide and ketoconazole both increase QTc interval. Contraindicated.

• isavuconazonium sulfate

  ketoconazole will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• isoniazid

  isoniazid decreases levels of ketoconazole by unspecified interaction mechanism. Contraindicated.

• ivabradine

  ketoconazole will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.

• lomitapide

  ketoconazole increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increases lomitapide levels several folds.

• lonafarnib

  ketoconazole 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

  ketoconazole will increase the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors increase systemic statin exposure and risk of myopathy, including rhabdomyolysis

• lurasidone

  ketoconazole 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.

• mavacamten

  ketoconazole will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.
  
  ketoconazole will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

• methadone

  ketoconazole will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  ketoconazole and methadone both increase QTc interval. Contraindicated.

• methylergonovine

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

• naloxegol

  ketoconazole 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

  ketoconazole will decrease the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• pacritinib

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

• pentamidine

  ketoconazole and pentamidine both increase QTc interval. Contraindicated.

• pimozide

  ketoconazole and pimozide both increase QTc interval. Contraindicated.
  
  ketoconazole increases levels of pimozide by decreasing metabolism. Contraindicated. Risk of QT interval prolongation.

• procainamide

  ketoconazole and procainamide both increase QTc interval. Contraindicated.

• quinidine

  ketoconazole will increase the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  quinidine and ketoconazole both increase QTc interval. Contraindicated.

• ranolazine

  ketoconazole will increase the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  ketoconazole and ranolazine both increase QTc interval. Contraindicated.

• silodosin

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

• simvastatin

  ketoconazole will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure
  
  ketoconazole increases toxicity of simvastatin by Other (see comment). Contraindicated. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• sirolimus

  ketoconazole increases levels of sirolimus by decreasing metabolism. Contraindicated.

• sotalol

  ketoconazole and sotalol both increase QTc interval. Contraindicated.

• triazolam

  ketoconazole increases levels of triazolam by decreasing metabolism. Contraindicated.

• ulipristal

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

• venetoclax

  ketoconazole 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

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

Serious - Use Alternative (209)

• abemaciclib

  ketoconazole will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Ketoconazole increases abemaciclib AUC by up to 16-fold.

• abrocitinib

  ketoconazole will increase the level or effect of abrocitinib by decreasing metabolism. Avoid or Use Alternate Drug. Abrocitinib is a CYP2C9 and CYP2C19 substrate. Drugs that are moderate-to-strong inhibitors of both CYP2C9 and CYP2C19 increase systemic exposure of abrocitinib and its active metabolites, which may increase adverse effects.

• acalabrutinib

  ketoconazole 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

  ketoconazole increases levels of ado-trastuzumab emtansine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors may increase DM1 (cytotoxic component of ado-trastuzumab) exposure and toxicity. Consider an alternant with no or minimal potential to inhibit CYP3A4. If use is unavoidable, consider delaying ado-trastuzumab until the strong CYP3A4 inhibitors have cleared (for approximately 3 elimination half-lives of the inhibitors) when possible. If ado-trastuzumab cannot be delayed, closely monitor patient for adverse reactions. .

• afatinib

  ketoconazole 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.

• almotriptan

  ketoconazole will increase the level or effect of almotriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. In patients concomitantly using strong CYP3A4 inhibitors, start almotriptan at 6.25 mg/day; not exceed 12.5 mg/day. Avoid coadministration of almotriptan and strong CYP3A4 inhibitors in patients with renal or hepatic impairment.

• alpelisib

  ketoconazole will increase the level or effect of alpelisib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of alpelisib (BCRP substrate) with a BCRP inhibitor may increase alpelisib concentration, which may increase the risk of toxicities. If unable to avoid or use alternant drugs, closely monitor for increased adverse reactions.

• aluminum hydroxide

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

• amiodarone

  ketoconazole will increase the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  amiodarone and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• amitriptyline

  amitriptyline and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• amoxapine

  amoxapine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• apalutamide

  apalutamide will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Apalutamide, a strong CYP3A4 inducer, may decrease the exposure of ketoconazole (a CYP3A4 substrate)

• apixaban

  ketoconazole will increase the level or effect of apixaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If taking apixaban dose >2.5 mg BID, decrease dose by 50% if coadministered with strong dual inhibitors of CYP3A4 and P-gp; if currently taking apixaban 2.5 mg PO BID, avoid coadministration with strong dual inhibitors of CYP3A4 and P-gp

• aprepitant

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

• avanafil

  ketoconazole will increase the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP3A4 inhibitors may reduce avanafil clearance increasing systemic exposure to avanafil; significantly increased levels may result in significant adverse events including severe hypotension, syncope, visual changes, and priapism. Coadministration with strong CYP3A4 is contraindicated.

• avapritinib

  ketoconazole 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

  ketoconazole 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%. If strong CYP3A4 inhibitor is discontinued, axitinib dose should changed (after 3-5 half lives of the inhibitor) to that used before initiating the inhibitor.

• bazedoxifene/conjugated estrogens

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

• bedaquiline

  ketoconazole 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

• belinostat

  ketoconazole will increase the level or effect of belinostat by decreasing metabolism. Avoid or Use Alternate Drug. Strong UGT inhibitors decrease metabolism of belinostat; reduce belinostat starting dose to 750 mg/m2 when coadministered with UGT inhibitors or in patients known to be homozygous for the UGT1A1*28 allele

• bosutinib

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

• brigatinib

  ketoconazole 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

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

• budesonide

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

• buprenorphine

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

• buprenorphine transdermal

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

• cabazitaxel

  ketoconazole will increase the level or effect of cabazitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, consider reducing the cabazitaxel dose by 25%.

• cabozantinib

  ketoconazole 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.

• calcium carbonate

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

• carbamazepine

  ketoconazole will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid combination for 2 weeks before and during ketoconazole use if possible. Monitor plasma levels when used concomitantly.

• ceritinib

  ketoconazole 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.

• chlorpromazine

  chlorpromazine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• cilostazol

  ketoconazole will increase the level or effect of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Dose reduction to 50 mg twice daily should be considered

• cimetidine

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

• cinacalcet

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

• clarithromycin

  clarithromycin and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.
  
  ketoconazole will increase the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• clomipramine

  clomipramine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• clopidogrel

  ketoconazole decreases effects of clopidogrel by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug. Clopidogrel efficacy may be reduced by drugs that inhibit CYP2C19. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. Clopidogrel is metabolized to this active metabolite in part by CYP2C19. .

• clozapine

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

• cobicistat

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

• cobimetinib

  ketoconazole 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

  ketoconazole 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, vaginal

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

• copanlisib

  ketoconazole 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.

• cortisone

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

• crizotinib

  ketoconazole increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. See prescribing information for precise dosage modification.

• dabigatran

  ketoconazole will increase the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Atrial fibrillation: Decrease dabigatran dose when coadministered with ketoconazole if CrCl is 30-50 mL/min. Avoid coadministering dabigatran with ketoconazole if CrCl <30 mL/min. DVT/PE treatment: Avoid coadministering dabigatran with ketoconazole if CrCl <50 mL/min

• dabrafenib

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

• daridorexant

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

• darifenacin

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

• darunavir

  ketoconazole, darunavir. Either increases effects of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Specific dosage recommendations for ketoconazole are not available when coadministered with darunavir. .

• dasatinib

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

• desipramine

  desipramine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• dexamethasone

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

• dexlansoprazole

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

• diazepam

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

• dofetilide

  dofetilide and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• doxepin

  doxepin and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• droperidol

  droperidol and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• edoxaban

  ketoconazole 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

• elacestrant

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

• elbasvir/grazoprevir

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

• eletriptan

  ketoconazole increases levels of eletriptan by decreasing metabolism. Contraindicated. Separate by 72 hours.

• eluxadoline

  ketoconazole increases levels of eluxadoline by decreasing metabolism. Avoid or Use Alternate Drug. Decrease eluxadoline dose to 75 mg PO BID if coadministered with OATP1B1 inhibitors. .

• encorafenib

  ketoconazole will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, reduce encorafenib dose to 150 mg/day if current dose is 450 mg/day and 75 mg/day if current dose is 150-300mg/day. After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

• entrectinib

  ketoconazole 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

  enzalutamide will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ketoconazole with strong CYP3A4 inducers from 2 weeks and during treatment with ketoconazole tablets. If use is unavoidable, monitor antifungal activity and increase ketoconazole if necessary.

• epinephrine

  epinephrine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• epinephrine racemic

  epinephrine racemic and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• eplerenone

  ketoconazole increases levels of eplerenone by decreasing metabolism. Contraindicated.

• erdafitinib

  ketoconazole will increase the level or effect of erdafitinib by altering metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration with strong CYP3A4/CYP2C9 inhibitors, monitor closely for adverse reactions and consider decreasing dose accordingly. If strong CYP3A4/CYP2C9 inhibitor is discontinued, consider increasing erdafitinib dose in the absence of any drug-related toxicities.

• erlotinib

  ketoconazole will increase the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, monitor for erlotinib toxicities. If severe toxicities do occur, reduce erlotinib dose in 50-mg decrements.
  
  ketoconazole will increase the level or effect of erlotinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• erythromycin base

  erythromycin base and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  erythromycin ethylsuccinate and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  erythromycin lactobionate and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin stearate

  erythromycin stearate and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• esomeprazole

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

• everolimus

  ketoconazole will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  ketoconazole will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• famotidine

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

• fedratinib

  ketoconazole 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.
  
  ketoconazole will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

• felodipine

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

• fesoterodine

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

• fexinidazole

  ketoconazole 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.

• fluconazole

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

• fluphenazine

  fluphenazine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• fluticasone intranasal

  ketoconazole 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.

• formoterol

  formoterol and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• fosamprenavir

  ketoconazole will increase the level or effect of fosamprenavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Dose reduction of ketoconazole may be needed for patients receiving >400 mg ketoconazole day. When coadministered with fosamprenavir with ritonavir, ketoconazole doses (>200 mg/day) are not recommended.

• fosaprepitant

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

• futibatinib

  ketoconazole will increase the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inhibitors may increase incidence/severity of futibatinib toxicities.

• gilteritinib

  ketoconazole 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. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.

• glasdegib

  ketoconazole will increase the level or effect of glasdegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternate therapies that are not strong CYP3A inhibitors or monitor for increased risk of adverse effects, including QTc interval prolongation.

• haloperidol

  haloperidol and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• ibrutinib

  ketoconazole 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 ketoconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

• idelalisib

  ketoconazole 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

• iloperidone

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

• imipramine

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

• infigratinib

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

• irinotecan

  ketoconazole will increase the level or effect of irinotecan by decreasing metabolism. Avoid or Use Alternate Drug. UGT1A1 inhibitors decrease irinotecan metabolism
  
  ketoconazole will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• irinotecan liposomal

  ketoconazole will increase the level or effect of irinotecan liposomal by decreasing metabolism. Avoid or Use Alternate Drug. UGT1A1 inhibitors decrease irinotecan metabolism
  
  ketoconazole will increase the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. UGT1A1 inhibitors decrease irinotecan metabolism

• itraconazole

  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.

• ivosidenib

  ketoconazole will increase the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with ivosidenib or replace with alternate therapies. 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 the recommended dose of 500 mg qDay. Monitor for increased risk of QTc interval prolongation.
  
  ivosidenib will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• ixabepilone

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

• lansoprazole

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

• lapatinib

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

• larotrectinib

  ketoconazole 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

  ketoconazole 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.

• lemborexant

  ketoconazole 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.

• lenacapavir

  ketoconazole will increase the level or effect of lenacapavir by Other (see comment). Avoid or Use Alternate Drug. Drugs that inhibit P-gp, UGT1A1, and strongly inhibit CYP3A may significantly increase lenacapavir plasma concentrations.

• leniolisib

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

• lofepramine

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

• lorlatinib

  ketoconazole 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.

• lumacaftor/ivacaftor

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

• lumefantrine

  ketoconazole will increase the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  ketoconazole and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

• lurbinectedin

  ketoconazole will increase the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce lurbinectedin dose by 50%. After strong CYP3A inhibitor discontinued for 5 half-lives, increase lurbinectedin to dose used before coadministration.

• macimorelin

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

• macitentan

  ketoconazole 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 ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• mefloquine

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

• mestranol

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

• methylprednisolone

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

• midazolam

  ketoconazole will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  ketoconazole increases levels of midazolam by decreasing metabolism. Contraindicated.

• midazolam intranasal

  ketoconazole 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

  ketoconazole 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

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

• mizolastine

  ketoconazole increases levels of mizolastine by decreasing metabolism. Contraindicated.

• mobocertinib

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

• moxifloxacin

  ketoconazole and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• neratinib

  ketoconazole 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

  nevirapine decreases levels of ketoconazole by increasing metabolism. Contraindicated.
  
  ketoconazole will increase the level or effect of nevirapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nilotinib

  ketoconazole will increase the level or effect of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is avoidable, reduce nilotinib dosage to 300 mg PO qDay (resistant or intolerant Ph+ CML patients) or to 200 mg PO qDay (newly diagnosed Ph+ CML-CP patients). If strong inhibitor is discontinued, allow a washout period before adjusting nilotinib dose upward to indicated dose. Monitor closely for QT prolongation.
  
  ketoconazole and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.

• nizatidine

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

• nortriptyline

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

• octreotide

  ketoconazole and octreotide both increase QTc interval. Avoid or Use Alternate Drug.

• octreotide (Antidote)

  ketoconazole and octreotide (Antidote) both increase QTc interval. Avoid or Use Alternate Drug.

• olaparib

  ketoconazole 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 100 mg PO BID.

• omaveloxolone

  ketoconazole will increase the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unavoidable, reduce omaveloxolone dose to 50 mg/day. Closely monitor and discontinue if adverse effects emerge.

• omeprazole

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

• ozanimod

  ketoconazole increases toxicity of ozanimod by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of ozanimod (a BCRP substrate) with BCRP inhibitors increases the exposure of the minor (RP101988, RP101075) and major active metabolites (CC112273, CC1084037) of ozanimod, which may increase the risk of ozanimod adverse reactions. .

• palbociclib

  ketoconazole 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.

• palovarotene

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

• pantoprazole

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

• pazopanib

  ketoconazole will increase the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of pazopanib with strong CYP3A4 inhibitors if possible; if must coadminister, decrease pazopanib dose to 400 mg/day

• pemigatinib

  ketoconazole 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 ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• pexidartinib

  ketoconazole 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.
  
  ketoconazole will increase the level or effect of pexidartinib by Other (see comment). Avoid or Use Alternate Drug. Pexdartinib is a UGTA4 substrate. Reduce pexdartinib dose if concomitant use of UGT inhibitors cannot be avoided (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pexidartinib dose.
  
  ketoconazole and pexidartinib both increase inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

• pimavanserin

  ketoconazole 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.

• pirtobrutinib

  ketoconazole will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.

• pomalidomide

  ketoconazole increases levels of pomalidomide by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.
  
  ketoconazole increases levels of pomalidomide by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• ponatinib

  ketoconazole increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.

• pralsetinib

  ketoconazole will increase the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid use with drugs that are both strong CYP3A4 and P-gp inhibitors when possible. If combined, reduce pralsetinib dose to 200 mg qDay (if current dose is 300-400 mg qDay) or 100 mg qDay ( if current dose is 200 mg qDay) After CYP3A4 and P-gp inhibitor has been discontinued for 3-5 elimination half-lives, resume pralsetinib at the dose taken before initiating the inhibitor.

• prednisone

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

• pretomanid

  ketoconazole, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

• prochlorperazine

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

• promazine

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

• promethazine

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

• protriptyline

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

• rabeprazole

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

• red yeast rice

  ketoconazole 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

  ketoconazole 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

• repaglinide

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

• ribociclib

  ketoconazole, ribociclib. Either increases effects of the other 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.
  
  ribociclib will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  ketoconazole increases toxicity of ribociclib by QTc interval. Avoid or Use Alternate Drug.

• rifabutin

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

• rimegepant

  ketoconazole will increase the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  ketoconazole will increase the level or effect of rimegepant by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
  
  ketoconazole will increase the level or effect of rimegepant by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of rimegepant (a BCRP substrate) with inhibitors of BCRP.

• rivaroxaban

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

• rosuvastatin

  ketoconazole increases toxicity of rosuvastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• ruxolitinib

  ketoconazole will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If starting ruxolitinib and currently treated with strong CYP3A4 inhibitors, start ruxolitinib at 5 mg BID in polycythemia vera. In myelofibrosis patients, start ruxolitinib at 10 mg BID in those with platelet counts 100 x10^9/L or greater, or 5 mg qDay in those with platelet counts at 50 to 100 x 10^9/L. In patients currently on ruxolitinib and starting a CYP3A4 inhibitor, reduce ruxolitinib dose by 50% (ie, 10 mg BID to 5 mg BID). Avoid strong CYP3A4 inhibitors in patients currently treated with ruxolitinib 5 mg qDay.

• ruxolitinib topical

  ketoconazole will increase the level or effect of ruxolitinib topical 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

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

• salmeterol

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

• saquinavir

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

• selpercatinib

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

• selumetinib

  ketoconazole 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.

• sildenafil

  ketoconazole will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP3A4 inhibitors and sildenafil (for pulmonary arterial hypertension) is not recommended. When used for erectile dysfunction, consider reducing initial sildenafil dose of 25 mg in patients also taking a strong CYP3A4 inhibitor and monitor for sildenafil toxicities (eg, dyspepsia, headache, hypotension).

• siponimod

  ketoconazole will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.
  
  ketoconazole 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

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

• sodium bicarbonate

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

• solifenacin

  ketoconazole will increase the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Do not exceed a 5 mg/day dosage of solifenacin when concomitantly used with strong CYP3A4 inhibitors.

• sonidegib

  ketoconazole 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.

• sparsentan

  ketoconazole, sparsentan. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. If unavoidable, interrupt treatment with sparsentan. When resuming sparsentan, consider dose titration. .

• stiripentol

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

• sunitinib

  ketoconazole will increase the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, consider reducing the sunitinib dose to a minimum dosage as 37.5 mg qDay (GIST and RCC), on a schedule of 4 weeks on treatment followed by 2 weeks off. For pNET patients, consider reducing to25 mg qDay.

• suvorexant

  ketoconazole 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.

• tacrolimus

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

• tadalafil

  ketoconazole will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP3A4 inhibitors may reduce tadalafil clearance increasing systemic exposure to tadalafil; significantly increased levels may result in significant adverse events including severe hypotension, syncope, visual changes, and priapism.

• talazoparib

  ketoconazole will increase the level or effect of talazoparib by Other (see comment). Avoid or Use Alternate Drug. BCRP inhibitors may increase systemic exposure of talazoparib (a BCRP substrate). If coadministration cannot be avoided, monitor for potential adverse reactions.

• tamsulosin

  ketoconazole increases levels of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for increased toxicity.

• tazemetostat

  ketoconazole 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

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

• theophylline

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

• thioridazine

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

• ticagrelor

  ketoconazole increases levels of ticagrelor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Ticagrelor is metabolized by CYP3A4/5. Avoid use with strong CYP3A inhibitors.

• tofacitinib

  ketoconazole increases levels of tofacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce tofacitinib dose to 5 mg qDay (psoriatic arthritis and rheumatoid arthritis) when coadministered with potent CYP3A4 inhibitors. Refer to prescribing information for other indications. .

• tolterodine

  ketoconazole will increase the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Do not exceed tolterodine dose of 2mg qDay when coadministered with strong CYP3A4 inhibitors.

• tolvaptan

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

• topotecan

  ketoconazole 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

• toremifene

  ketoconazole increases levels of toremifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Metabolism of toremifene may be inhibited by drugs known to inhibit CYP3A4 hepatic enzymes.

• trabectedin

  ketoconazole 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

  ketoconazole will increase the level or effect of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  trazodone and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• triamcinolone acetonide injectable suspension

  ketoconazole 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 ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• trimipramine

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

• ubrogepant

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

• vemurafenib

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

• vilazodone

  ketoconazole 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 vilazodone daily dose to 20 mg.

• vorapaxar

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

• ziprasidone

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

Monitor Closely (305)

• alfentanil

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

• alfuzosin

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

• aliskiren

  ketoconazole will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• alosetron

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

• aluminum hydroxide

  aluminum hydroxide decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

• amikacin

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

• amitriptyline

  ketoconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• amlodipine

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

• apomorphine

  ketoconazole and apomorphine both increase QTc interval. Use Caution/Monitor.

• aripiprazole

  ketoconazole will increase the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce aripiprazole oral dose by 50% of the usual dose when concomitantly using a strong CYP3A4 inhibitor, and further to 25% of the usual dose in patients who are also receiving strong CYP2D6 inhibitors (eg, paroxetine, quinidine) or who are CYP2D6 poor metabolizers. Consider dose reductions to 25% of the usual dose when combining a strong CYP3A4 inhibitor with a less potent CYP2D6 inhibitor initially and then adjusted to achieve a favorable clinical response.

• armodafinil

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

• arsenic trioxide

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

• artemether/lumefantrine

  ketoconazole will increase the level or effect of artemether/lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole and artemether/lumefantrine both increase QTc interval. Use Caution/Monitor.

• atazanavir

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

• atogepant

  ketoconazole will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Recommended atogepant dosage is 10 mg PO qDay when coadministered with strong CYP3A4 inhibitors.

• atorvastatin

  ketoconazole will increase the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Consider the risk/benefit of concomitant use of ketoconazole with atorvastatin. Monitor for signs and symptoms of myopathy particularly during initiation and dose titration of either drug.
  
  ketoconazole will increase the level or effect of atorvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• avatrombopag

  ketoconazole will increase the level or effect of avatrombopag by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of avatrombopag with a moderate or strong dual CYP2C9/3A4 inhibitor requires a decreased avatrombopag starting dose to 20 mg PO TID.

• azithromycin

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

• bazedoxifene/conjugated estrogens

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

• benzhydrocodone/acetaminophen

  ketoconazole 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

  ketoconazole 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.
  
  ketoconazole increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

• betrixaban

  ketoconazole 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

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

• bortezomib

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

• bosentan

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

• brentuximab vedotin

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

• brexpiprazole

  ketoconazole 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.
  
  ketoconazole will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• budesonide

  ketoconazole will increase the level or effect of budesonide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole increases effects of budesonide by decreasing metabolism. Use Caution/Monitor.

• buprenorphine subdermal implant

  ketoconazole 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

  ketoconazole 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

  ketoconazole will increase the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce starting dose of buspirone to 2.5 mg PO qDay. Adjust dose based on clinical assessment.

• busulfan

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

• calcifediol

  ketoconazole, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

• calcitriol

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

• calcium carbonate

  calcium carbonate decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

• cannabidiol

  ketoconazole will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

• capmatinib

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

• carbamazepine

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

• cariprazine

  ketoconazole 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.

• carvedilol

  ketoconazole will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• ceritinib

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

• cevimeline

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

• chlordiazepoxide

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

• chlorpropamide

  ketoconazole increases levels of chlorpropamide by decreasing metabolism. Use Caution/Monitor.

• cholic acid

  ketoconazole increases toxicity of cholic acid by decreasing elimination. Modify Therapy/Monitor Closely. Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP). May exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. If concomitant use is necessary, monitor serum transaminases and bilirubin.

• ciclesonide inhaled

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

• cilostazol

  ketoconazole increases toxicity of cilostazol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider decreasing cilostazol dose; moderate CYP2C19 inhibitors may increase serum levels of 3,4-dehydrocilostazol (active metabolite); dose reduction to 50 mg twice daily should be considered.

• cimetidine

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

• clarithromycin

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

• clobazam

  ketoconazole will increase the level or effect of clobazam by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Dosage adjustment may be required; CYP2C19 inhibitors may result in increased exposure to N-desmethylclobazam (active metabolite).

• clomipramine

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

• clonazepam

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

• clopidogrel

  ketoconazole decreases effects of clopidogrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clopidogrel efficacy may be reduced by drugs that inhibit CYP3A4. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. Clopidogrel is metabolized to this active metabolite in part by CYP3A4. .

• clorazepate

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

• cobicistat

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

• codeine

  ketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• conjugated estrogens

  ketoconazole will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• conjugated estrogens, vaginal

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

• cortisone

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

• cyclophosphamide

  ketoconazole increases toxicity of cyclophosphamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cyclosporine

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

• dapsone

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

• darolutamide

  ketoconazole 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.

• daunorubicin

  ketoconazole 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 ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• deflazacort

  ketoconazole will increase the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease deflazacort dose to one-third of the recommended dose if coadministered with moderate or strong CYP3A4 inhibitors.
  
  ketoconazole will increase the level or effect of deflazacort by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole and deflazacort both decrease serum potassium. Use Caution/Monitor.

• dexamethasone

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

• diazepam intranasal

  ketoconazole will increase the level or effect of diazepam intranasal by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Strong or moderate CYP2C19 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.
  
  ketoconazole 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.

• diclofenac

  ketoconazole will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Do not exceed diclofenac dose of 50 mg BID

• didanosine

  didanosine will decrease the level or effect of ketoconazole 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

  ketoconazole 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

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

• diltiazem

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

• docetaxel

  ketoconazole will increase the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of docetaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• dolasetron

  dolasetron and ketoconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• donepezil

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

• doxorubicin

  ketoconazole will increase the level or effect of doxorubicin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of doxorubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• doxorubicin liposomal

  ketoconazole will increase the level or effect of doxorubicin liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of doxorubicin liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• dronabinol

  ketoconazole will increase the level or effect of dronabinol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Dronabinol is a CYP2C9 substrate.
  
  ketoconazole will increase the level or effect of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dronabinol is a CYP3A4 substrate.

• dutasteride

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

• duvelisib

  ketoconazole 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.
  
  ketoconazole will increase the level or effect of duvelisib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of duvelisib by Other (see comment). Use Caution/Monitor. Coadministration of duvelisib (a BCRP substrate) with a BCRP transport inhibitor may increase levels or effects of duvelisib.

• efavirenz

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

• elagolix

  ketoconazole 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.

• eluxadoline

  ketoconazole increases levels of eluxadoline by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. As a precautionary measure due to incomplete information on the metabolism of eluxadoline, use caution when coadministered with strong CYP2C9/10 inhibitors.

• elvitegravir

  ketoconazole, elvitegravir. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministered, do not exceed ketoconazole 200 mg/day; no dose adjustment needed for elvitegravir.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  elvitegravir/cobicistat/emtricitabine/tenofovir DF, ketoconazole. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Both cobicistat and ketoconazole are CYP3A4 inhibitors; do not exceed ketoconazole dose of 200 mg/day.
  
  ketoconazole will increase the level or effect of elvitegravir/cobicistat/emtricitabine/tenofovir DF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit ketoconazole to 200 mg/day when administered with elvitegravir/cobicistat/emtricitabine/tenofovir DF.

• encorafenib

  encorafenib, ketoconazole. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

• enfortumab vedotin

  ketoconazole 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.
  
  ketoconazole will increase the level or effect of enfortumab vedotin by Other (see comment). Use Caution/Monitor. Coadministration with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE) exposure, which may increase the risk of enfortumab vedotin toxicities. Closely monitor for signs of toxicities.

• eplerenone

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

• erythromycin base

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

• erythromycin ethylsuccinate

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

• erythromycin lactobionate

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

• erythromycin stearate

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

• estradiol

  ketoconazole will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• estradiol vaginal

  ketoconazole 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

  ketoconazole will increase the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of estrogens conjugated synthetic by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• estrogens esterified

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

• estropipate

  ketoconazole will increase the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of estropipate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• eszopiclone

  ketoconazole will increase the level or effect of eszopiclone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Eszopiclone dose should not exceed 2 mg/day when coadministered with strong CYP3A4 inhibitors.

• ethinylestradiol

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

• ethosuximide

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

• ethotoin

  ketoconazole will increase the level or effect of ethotoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• etonogestrel

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

• etoposide

  ketoconazole will increase the level or effect of etoposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of etoposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• etravirine

  ketoconazole will increase the level or effect of etravirine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  ketoconazole, etravirine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Ketoconazole, a CYP3A4 inhibitor and substrate, may increase plasma concentrations of etravirine. Etravirine may decrease ketoconazole plasma concentrations. Consider dose adjustment of ketoconazole depending on the other coadministered drugs.

• eucalyptus

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

• felbamate

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

• fentanyl

  ketoconazole will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fentanyl intranasal

  ketoconazole will increase the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fentanyl transdermal

  ketoconazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fentanyl transmucosal

  ketoconazole will increase the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• finasteride

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

• fingolimod

  ketoconazole increases levels of fingolimod by Other (see comment). Use Caution/Monitor. Comment: Mechanism: affecting hepatic enzyme CYP4F2 metabolism Monitor for adverse events of fingolimod when concomitantly used with ketoconazole.

• flecainide

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

• fludrocortisone

  ketoconazole will increase the level or effect of fludrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of fludrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• flunisolide inhaled

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

• fluoxetine

  fluoxetine and ketoconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• flurazepam

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

• fluticasone furoate

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

• fluticasone inhaled

  ketoconazole 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

• fluvastatin

  ketoconazole increases toxicity of fluvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• fluvoxamine

  fluvoxamine and ketoconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• foscarnet

  foscarnet and ketoconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• fosphenytoin

  ketoconazole will increase the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• fostamatinib

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

• galantamine

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

• gefitinib

  ketoconazole 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.

• gentamicin

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

• glecaprevir/pibrentasvir

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

• glimepiride

  ketoconazole increases levels of glimepiride by decreasing metabolism. Use Caution/Monitor.

• glipizide

  ketoconazole increases levels of glipizide by decreasing metabolism. Use Caution/Monitor.

• glyburide

  ketoconazole increases levels of glyburide by decreasing metabolism. Use Caution/Monitor.
  
  ketoconazole increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

• grapefruit

  grapefruit decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• guanfacine

  ketoconazole will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inhibitors significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if coadministered, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available.

• haloperidol

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

• hydrocodone

  ketoconazole will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

• hydrocortisone

  ketoconazole will increase the level or effect of hydrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of hydrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• hydroxyprogesterone caproate (DSC)

  ketoconazole will increase the level or effect of hydroxyprogesterone caproate (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ifosfamide

  ketoconazole 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

  iloperidone and ketoconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• imatinib

  ketoconazole will increase the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of imatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• imipramine

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

• indacaterol, inhaled

  ketoconazole increases levels of indacaterol, inhaled by Other (see comment). Use Caution/Monitor. 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.

• indinavir

  ketoconazole 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 PO q8hr when administering ketoconazole concurrently.
  
  ketoconazole will increase the level or effect of indinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• irinotecan

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

• irinotecan liposomal

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

• isradipine

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

• istradefylline

  ketoconazole 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.

• itraconazole

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

• ivacaftor

  ketoconazole 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

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

• lacosamide

  ketoconazole increases levels of lacosamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients with renal or hepatic impairment who are taking strong CYP3A4 and CYP2C9 inhibitors may have a significant increase in exposure to lacosamide. Dose reduction may be necessary in these patients.
  
  ketoconazole increases levels of lacosamide by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Patients with renal or hepatic impairment who are taking strong CYP3A4 and CYP2C9 inhibitors may have a significant increase in exposure to lacosamide. Dose reduction may be necessary in these patients.

• lansoprazole

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

• lapatinib

  ketoconazole will increase the level or effect of lapatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole and lapatinib both increase QTc interval. Modify Therapy/Monitor Closely.

• lesinurad

  ketoconazole will increase the level or effect of lesinurad by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• letermovir

  ketoconazole increases effects of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.
  
  letermovir increases levels of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levamlodipine

  ketoconazole 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.

• levofloxacin

  ketoconazole and levofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

• levomilnacipran

  ketoconazole 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

  ketoconazole 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

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

• loperamide

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

• lopinavir

  ketoconazole will increase the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Ketoconazole doses > 200 mg/day is not recommended when concurrently used with lopinavir/ritonavir.

• loratadine

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

• losartan

  ketoconazole will increase the level or effect of losartan by affecting hepatic enzyme CYP2C9/10 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.

• lovastatin

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

• lumacaftor/ivacaftor

  ketoconazole 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.

• lumateperone

  ketoconazole will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 10.5 mg/day if coadministered with strong CYP3A4 inhibitors.

• maraviroc

  ketoconazole will increase the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decrease maraviroc dose to 150 mg BID when coadministered with strong CYP3A4 inhibitors. Refer to prescribing for pediatric dosage modifications.
  
  ketoconazole will increase the level or effect of maraviroc by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• marijuana

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

• medroxyprogesterone

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

• mestranol

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

• methylprednisolone

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

• mipomersen

  mipomersen, ketoconazole. 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

  ketoconazole will increase the level or effect of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce mirtazapine dose if coadministration of strong CYP3A4 inhibitor is necessary. Once CYP3A4 inhibitor is discontinued, consider increasing mirtazapine dose.

• mirvetuximab soravtansine

  ketoconazole will increase the level or effect of mirvetuximab soravtansine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with strong CYP3A4 inhibitors may increase unconjugated DM4 (a CYP3A4 substrate and the cytotoxic component of the antibody drug conjugate for mirvetuximab soravtansine) exposure, which may increase the risk of adverse reactions.

• modafinil

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

• mometasone inhaled

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

• mometasone, intranasal

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

• montelukast

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

• naldemedine

  ketoconazole 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.
  
  ketoconazole 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.

• nateglinide

  ketoconazole will increase the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• nefazodone

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

• nelfinavir

  ketoconazole will increase the level or effect of nelfinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• neomycin PO

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

• netupitant/palonosetron

  ketoconazole 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

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

• nifedipine

  ketoconazole will increase the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole increases levels of nifedipine by decreasing metabolism. Use Caution/Monitor.

• nilotinib

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

• nimodipine

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

• nintedanib

  ketoconazole 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 .

• nirmatrelvir

  nirmatrelvir will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit ketoconazole adult dose to 200 mg/day if coadministered with ritonavir.

• nirmatrelvir/ritonavir

  nirmatrelvir/ritonavir will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit ketoconazole adult dose to 200 mg/day if coadministered with ritonavir.

• nitrendipine

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

• norgestrel

  ketoconazole will increase the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may increase systemic concentration of norgestrel, which may increase risk for adverse effects

• ofloxacin

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

• oliceridine

  ketoconazole will increase the level or effect of oliceridine by affecting hepatic enzyme CYP2D6 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.
  
  ketoconazole 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.

• ondansetron

  ketoconazole will increase the level or effect of ondansetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP-450 inhibitors may decrease clearance of ondansetron. However, no dosage adjustment for ondansetron is recommended

• osilodrostat

  ketoconazole 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.

• ospemifene

  ketoconazole increases levels of ospemifene by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  ketoconazole increases levels of ospemifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• oxybutynin

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

• oxycodone

  ketoconazole 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

  ketoconazole will increase the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of paclitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• paclitaxel protein bound

  ketoconazole will increase the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of paclitaxel protein bound by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• paliperidone

  ketoconazole will increase the level or effect of paliperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole and paliperidone both increase QTc interval. Modify Therapy/Monitor Closely.

• panobinostat

  ketoconazole 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.

• parecoxib

  ketoconazole will increase the level or effect of parecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of parecoxib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• paricalcitol

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

• paromomycin

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

• paroxetine

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

• pazopanib

  ketoconazole and pazopanib both increase QTc interval. Use Caution/Monitor.

• perampanel

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

• phenytoin

  ketoconazole will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• pimozide

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

• pioglitazone

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

• pitavastatin

  ketoconazole increases toxicity of pitavastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• polatuzumab vedotin

  ketoconazole 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.

• posaconazole

  ketoconazole will increase the level or effect of posaconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• pravastatin

  ketoconazole increases toxicity of pravastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• praziquantel

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

• prednisolone

  ketoconazole will increase the level or effect of prednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of prednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• prednisone

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

• progesterone intravaginal gel

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

• progesterone micronized

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

• progesterone, natural

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

• propafenone

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

• quetiapine

  ketoconazole will increase the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce quetiapine dose to one sixth of the original dose when coadministered with a strong CYP3A4 inhibitor.

• quinine

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

• quizartinib

  ketoconazole will increase the level or effect of quizartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce quizartinib dosage to 26.5 mg qDay (if current dosage is 53 mg/day) or 17.7 mg qDay (if current dosage is 26.5 mg/day or 35.4 mg/day) when coadministered with strong CYP3A inhibitors. If current dosage is 17.7 mg qDay, interrupt quizartinib for the duration of strong CYP3A inhibitor use. After discontinuation of a strong CYP3A inhibitor for 5 half-lives, resume quizartinib dose that was taken before initiating the strong inhibitor.

• rabeprazole

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

• ramelteon

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

• rifabutin

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

• rifampin

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

• rifaximin

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

• rilpivirine

  ketoconazole 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

  ketoconazole 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
  
  ketoconazole 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
  
  ketoconazole will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider a starting riociguat dose of 0.5 mg TID when initiating riociguat in patients receiving strong CYP and P-gp/BCRP inhibitors. Monitor for signs and symptoms of hypotension on initiation and on treatment with strong CYP and P-gp/BCRP inhibitors.

• ripretinib

  ketoconazole 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

  ketoconazole will increase the level or effect of risperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole and risperidone both increase QTc interval. Modify Therapy/Monitor Closely.

• ritonavir

  ketoconazole will increase the level or effect of ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Ketoconazole dose is not to exceed 200 mg/day when concurrently used with ritonavir.
  
  ketoconazole will increase the level or effect of ritonavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• roflumilast

  ketoconazole increases levels of roflumilast by Other (see comment). Modify Therapy/Monitor Closely. Comment: Coadministration with dual inhibitors of CYP3A4 and CYP1A2 may increase systemic exposure and result in increased adverse reactions.
  
  ketoconazole will increase the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• romidepsin

  ketoconazole will increase the level or effect of romidepsin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of romidepsin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely.

• sacubitril/valsartan

  ketoconazole will increase the level or effect of sacubitril/valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

• saquinavir

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

• saxagliptin

  ketoconazole 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

• selexipag

  ketoconazole will increase the level or effect of selexipag by Other (see comment). Use Caution/Monitor. Selexipag is a ABCG2 (BCRP) substrate. Monitor selexipag for increased pharmacologic or adverse effects when coadministered with ABCG2 (BCRP) inhibitors.

• silodosin

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

• sirolimus

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

• sodium bicarbonate

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

• sodium sulfate/?magnesium sulfate/potassium chloride

  sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of ketoconazole by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol

  ketoconazole and sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol both decrease serum potassium. Modify Therapy/Monitor Closely.

• sodium sulfate/potassium sulfate/magnesium sulfate

  sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of ketoconazole by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• sodium zirconium cyclosilicate

  sodium zirconium cyclosilicate will decrease the level or effect of ketoconazole 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.

• St John's Wort

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

• streptomycin

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

• sucralfate

  sucralfate decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• sufentanil

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

• sufentanil SL

  ketoconazole will increase the level or effect of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider dosage reduction of sufentanil until stable drug effects are achieved. Monitor for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing sufentanil dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

• sulfamethoxazole

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

• tacrolimus

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

• tacrolimus ointment

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

• talazoparib

  ketoconazole will increase the level or effect of talazoparib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Talazoparib is a P-glycoprotein (P-gp) substrate; coadministration with P-gp inhibitors may increase talazoparib systemic exposure.

• tamoxifen

  ketoconazole, tamoxifen. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. CYP2C9/10 inhibition decreases tamoxifen metabolism to active metabolites.
  
  ketoconazole, tamoxifen. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inhibition decreases metabolism of tamoxifen to N-desmethyl tamoxifen (active metabolite with similar biologic activity).

• tamsulosin

  ketoconazole increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• tasimelteon

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

• telavancin

  ketoconazole and telavancin both increase QTc interval. Modify Therapy/Monitor Closely.

• teniposide

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

• terbinafine

  ketoconazole will increase the level or effect of terbinafine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  ketoconazole will decrease the level or effect of terbinafine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tezacaftor

  ketoconazole 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.

• tipranavir

  ketoconazole will increase the level or effect of tipranavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Ketoconazole dose is not to exceed 200 mg/day when concurrently used.

• tisotumab vedotin

  ketoconazole increases levels of tisotumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tisotumab vedotin?s active metabolite (MMAE) is a CYP3A4 substrate. Coadministration with strong CYP3A4 inhibitors may increase unconjugated MMAE systemic exposure and increase risk of adverse effects.

• tobramycin

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

• tolazamide

  ketoconazole increases levels of tolazamide by decreasing metabolism. Use Caution/Monitor.

• tolbutamide

  ketoconazole increases levels of tolbutamide by decreasing metabolism. Use Caution/Monitor.

• tolvaptan

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

• tramadol

  ketoconazole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May require decreased tramadol dose or adjustment of dosing interval; increased risk for serious adverse events including seizures and serotonin syndrome

• tretinoin

  ketoconazole increases levels of tretinoin by decreasing metabolism. Use Caution/Monitor.

• trimethoprim

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

• trimipramine

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

• tropisetron

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

• umeclidinium bromide/vilanterol inhaled

  ketoconazole 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

  ketoconazole 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

  ketoconazole 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.

• valoctocogene roxaparvovec

  ketoconazole and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.

• valsartan

  ketoconazole will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

• vandetanib

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

• vardenafil

  ketoconazole will increase the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministered with ketoconazole 400 mg/day, limit vardenafil dose to 2.5 mg/24 hr. If coadministered with ketoconazole 200 mg/day, limit vardenafil dose to 5 mg/24 hr.

• vemurafenib

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

• venlafaxine

  ketoconazole and venlafaxine both increase QTc interval. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of venlafaxine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• verapamil

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

• vilanterol/fluticasone furoate inhaled

  ketoconazole 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

  ketoconazole will increase the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of vinblastine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• vincristine

  ketoconazole will increase the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of vincristine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• vincristine liposomal

  ketoconazole will increase the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of vincristine liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• vinorelbine

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

• voclosporin

  voclosporin, ketoconazole. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

• vonoprazan

  vonoprazan will decrease the level or effect of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Separate administration by at least 1 hr before or 2 hr after ketoconazole.

• voriconazole

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

• warfarin

  ketoconazole will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• zaleplon

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

• zanubrutinib

  ketoconazole will increase the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce zanubrutinib (a CYP3A4 substrate) to 80 mg PO BID when coadministered with a moderate CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous zanubrutinib dose.

• zidovudine

  ketoconazole increases levels of zidovudine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ziprasidone

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

• zolpidem

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

• zonisamide

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

Minor (90)

• alosetron

  ketoconazole will increase the level or effect of alosetron by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• alvimopan

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

• ambrisentan

  ketoconazole will increase the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  ketoconazole will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• amikacin

  ketoconazole decreases levels of amikacin by unknown mechanism. Minor/Significance Unknown.

• amobarbital

  amobarbital will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  amobarbital decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• aprepitant

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

• armodafinil

  armodafinil will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  ketoconazole will increase the level or effect of armodafinil by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• artemether/lumefantrine

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

• atazanavir

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

• bosentan

  ketoconazole will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  bosentan will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• budesonide

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

• butabarbital

  butabarbital will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  butabarbital decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• butalbital

  butalbital will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• caffeine

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

• celecoxib

  ketoconazole will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• chlordiazepoxide

  ketoconazole increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

• conivaptan

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

• cortisone

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

• darifenacin

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

• dasatinib

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

• desloratadine

  ketoconazole increases levels of desloratadine by decreasing metabolism. Minor/Significance Unknown.

• dexamethasone

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

• DHEA, herbal

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

• doravirine

  ketoconazole will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

• efavirenz

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

• eslicarbazepine acetate

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

• etravirine

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

• fexofenadine

  ketoconazole 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 ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fludrocortisone

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

• flurbiprofen

  ketoconazole will increase the level or effect of flurbiprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fluvastatin

  ketoconazole will increase the level or effect of fluvastatin by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fosamprenavir

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

• fosaprepitant

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

• fosphenytoin

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

• ganaxolone

  ketoconazole, ganaxolone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Changes in ganaxolone exposures when coadministered with strong, moderate, or weak CYP3A4 inhibitors are not expected to be clinically significant.

• gentamicin

  ketoconazole decreases levels of gentamicin by unknown mechanism. Minor/Significance Unknown.

• grapefruit

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

• griseofulvin

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

• hydrocortisone

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

• ibuprofen

  ketoconazole will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ibuprofen IV

  ketoconazole will increase the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• indinavir

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

• isoniazid

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

• lapatinib

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

• loratadine

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

• losartan

  ketoconazole decreases effects of losartan by decreasing metabolism. Minor/Significance Unknown. 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.

• lumefantrine

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

• marijuana

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

• meloxicam

  ketoconazole will increase the level or effect of meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• mestranol

  ketoconazole decreases effects of mestranol by increasing metabolism. Minor/Significance Unknown. May also cause menstrual irregularities.

• methylprednisolone

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

• metronidazole

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

• miconazole vaginal

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

• nafcillin

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

• nelfinavir

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

• neomycin PO

  ketoconazole decreases levels of neomycin PO by unknown mechanism. Minor/Significance Unknown.

• nevirapine

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

• nifedipine

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

• nilotinib

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

• osimertinib

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

• oxcarbazepine

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

• pantoprazole

  ketoconazole will increase the level or effect of pantoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  ketoconazole will increase the level or effect of pantoprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• paromomycin

  ketoconazole decreases levels of paromomycin by unknown mechanism. Minor/Significance Unknown.

• pentobarbital

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

• piroxicam

  ketoconazole will increase the level or effect of piroxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• posaconazole

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

• prednisone

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

• primidone

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

• ramelteon

  ketoconazole will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• rifabutin

  ketoconazole increases levels of rifabutin by decreasing metabolism. Minor/Significance Unknown.

• rifampin

  ketoconazole decreases levels of rifampin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Only applies to oral preparations of both agents.

• rifapentine

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

• ritonavir

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

• rufinamide

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

• secobarbital

  secobarbital will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  secobarbital decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• sorafenib

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

• streptomycin

  ketoconazole decreases levels of streptomycin by unknown mechanism. Minor/Significance Unknown.

• sulfamethoxazole

  ketoconazole will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• tinidazole

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

• tobramycin

  ketoconazole decreases levels of tobramycin by unknown mechanism. Minor/Significance Unknown.

• tolbutamide

  ketoconazole will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• topiramate

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

• tretinoin topical

  ketoconazole increases levels of tretinoin topical by decreasing metabolism. Minor/Significance Unknown.

• verapamil

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

• voriconazole

  ketoconazole will increase the level or effect of voriconazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  voriconazole will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zafirlukast

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

• abemaciclib

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Ketoconazole increases abemaciclib AUC by up to 16-fold.

• abrocitinib

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of abrocitinib by decreasing metabolism. Avoid or Use Alternate Drug. Abrocitinib is a CYP2C9 and CYP2C19 substrate. Drugs that are moderate-to-strong inhibitors of both CYP2C9 and CYP2C19 increase systemic exposure of abrocitinib and its active metabolites, which may increase adverse effects.

• acalabrutinib

  Serious - Use Alternative (1)ketoconazole 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

  Serious - Use Alternative (1)ketoconazole increases levels of ado-trastuzumab emtansine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors may increase DM1 (cytotoxic component of ado-trastuzumab) exposure and toxicity. Consider an alternant with no or minimal potential to inhibit CYP3A4. If use is unavoidable, consider delaying ado-trastuzumab until the strong CYP3A4 inhibitors have cleared (for approximately 3 elimination half-lives of the inhibitors) when possible. If ado-trastuzumab cannot be delayed, closely monitor patient for adverse reactions. .

• afatinib

  Serious - Use Alternative (1)ketoconazole 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.

• alfentanil

  Monitor Closely (1)ketoconazole will increase the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• alfuzosin

  Contraindicated (1)ketoconazole increases levels of alfuzosin by decreasing metabolism. Contraindicated.Monitor Closely (1)ketoconazole will increase the level or effect of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• aliskiren

  Monitor Closely (2)ketoconazole will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• almotriptan

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of almotriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. In patients concomitantly using strong CYP3A4 inhibitors, start almotriptan at 6.25 mg/day; not exceed 12.5 mg/day. Avoid coadministration of almotriptan and strong CYP3A4 inhibitors in patients with renal or hepatic impairment.

• alosetron

  Monitor Closely (1)ketoconazole will increase the level or effect of alosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)ketoconazole will increase the level or effect of alosetron by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• alpelisib

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of alpelisib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of alpelisib (BCRP substrate) with a BCRP inhibitor may increase alpelisib concentration, which may increase the risk of toxicities. If unable to avoid or use alternant drugs, closely monitor for increased adverse reactions.

• alprazolam

  Contraindicated (1)ketoconazole increases levels of alprazolam by decreasing metabolism. Contraindicated.

• aluminum hydroxide

  Monitor Closely (1)aluminum hydroxide decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.Serious - Use Alternative (1)aluminum hydroxide will decrease the level or effect of ketoconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

• alvimopan

  Minor (1)ketoconazole will increase the level or effect of alvimopan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• ambrisentan

  Minor (2)ketoconazole will increase the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  ketoconazole will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• amikacin

  Monitor Closely (1)ketoconazole will increase the level or effect of amikacin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)ketoconazole decreases levels of amikacin by unknown mechanism. Minor/Significance Unknown.

• amiodarone

  Serious - Use Alternative (2)ketoconazole will increase the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  amiodarone and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• amitriptyline

  Monitor Closely (2)ketoconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• amlodipine

  Monitor Closely (1)ketoconazole will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• amobarbital

  Minor (2)amobarbital will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  amobarbital decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• amoxapine

  Serious - Use Alternative (1)amoxapine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• apalutamide

  Serious - Use Alternative (1)apalutamide will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Apalutamide, a strong CYP3A4 inducer, may decrease the exposure of ketoconazole (a CYP3A4 substrate)

• apixaban

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of apixaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If taking apixaban dose >2.5 mg BID, decrease dose by 50% if coadministered with strong dual inhibitors of CYP3A4 and P-gp; if currently taking apixaban 2.5 mg PO BID, avoid coadministration with strong dual inhibitors of CYP3A4 and P-gp

• apomorphine

  Monitor Closely (1)ketoconazole and apomorphine both increase QTc interval. Use Caution/Monitor.

• aprepitant

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)aprepitant will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• aripiprazole

  Monitor Closely (1)ketoconazole will increase the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce aripiprazole oral dose by 50% of the usual dose when concomitantly using a strong CYP3A4 inhibitor, and further to 25% of the usual dose in patients who are also receiving strong CYP2D6 inhibitors (eg, paroxetine, quinidine) or who are CYP2D6 poor metabolizers. Consider dose reductions to 25% of the usual dose when combining a strong CYP3A4 inhibitor with a less potent CYP2D6 inhibitor initially and then adjusted to achieve a favorable clinical response.

• armodafinil

  Monitor Closely (1)ketoconazole will increase the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (2)armodafinil will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  ketoconazole will increase the level or effect of armodafinil by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• arsenic trioxide

  Monitor Closely (1)arsenic trioxide and ketoconazole both increase QTc interval. Use Caution/Monitor.

• artemether/lumefantrine

  Monitor Closely (2)ketoconazole will increase the level or effect of artemether/lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole and artemether/lumefantrine both increase QTc interval. Use Caution/Monitor.Minor (1)artemether/lumefantrine will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• atazanavir

  Monitor Closely (1)ketoconazole will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)atazanavir will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• atogepant

  Monitor Closely (1)ketoconazole will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Recommended atogepant dosage is 10 mg PO qDay when coadministered with strong CYP3A4 inhibitors.

• atorvastatin

  Monitor Closely (2)ketoconazole will increase the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Consider the risk/benefit of concomitant use of ketoconazole with atorvastatin. Monitor for signs and symptoms of myopathy particularly during initiation and dose titration of either drug.
  
  ketoconazole will increase the level or effect of atorvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• avanafil

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP3A4 inhibitors may reduce avanafil clearance increasing systemic exposure to avanafil; significantly increased levels may result in significant adverse events including severe hypotension, syncope, visual changes, and priapism. Coadministration with strong CYP3A4 is contraindicated.

• avapritinib

  Serious - Use Alternative (1)ketoconazole 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.

• avatrombopag

  Monitor Closely (1)ketoconazole will increase the level or effect of avatrombopag by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of avatrombopag with a moderate or strong dual CYP2C9/3A4 inhibitor requires a decreased avatrombopag starting dose to 20 mg PO TID.

• axitinib

  Serious - Use Alternative (1)ketoconazole 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%. If strong CYP3A4 inhibitor is discontinued, axitinib dose should changed (after 3-5 half lives of the inhibitor) to that used before initiating the inhibitor.

• azithromycin

  Monitor Closely (1)azithromycin and ketoconazole both increase QTc interval. Use Caution/Monitor.

• bazedoxifene/conjugated estrogens

  Monitor Closely (1)ketoconazole will increase the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole will increase the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• bedaquiline

  Serious - Use Alternative (1)ketoconazole 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

• belinostat

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of belinostat by decreasing metabolism. Avoid or Use Alternate Drug. Strong UGT inhibitors decrease metabolism of belinostat; reduce belinostat starting dose to 750 mg/m2 when coadministered with UGT inhibitors or in patients known to be homozygous for the UGT1A1*28 allele

• benzhydrocodone/acetaminophen

  Monitor Closely (1)ketoconazole 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

  Monitor Closely (2)ketoconazole 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.
  
  ketoconazole increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

• betrixaban

  Monitor Closely (1)ketoconazole 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

  Monitor Closely (1)ketoconazole will increase the level or effect of bexarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• bortezomib

  Monitor Closely (1)ketoconazole will increase the level or effect of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• bosentan

  Monitor Closely (1)ketoconazole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (2)ketoconazole will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  bosentan will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• bosutinib

  Serious - Use Alternative (2)ketoconazole 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.
  
  ketoconazole increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• brentuximab vedotin

  Monitor Closely (1)ketoconazole increases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor patients for adverse reactions. .

• brexpiprazole

  Monitor Closely (2)ketoconazole 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.
  
  ketoconazole will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• brigatinib

  Serious - Use Alternative (1)ketoconazole 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

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of bromocriptine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• budesonide

  Monitor Closely (2)ketoconazole will increase the level or effect of budesonide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole increases effects of budesonide by decreasing metabolism. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole will increase the level or effect of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)budesonide will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• buprenorphine

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• buprenorphine subdermal implant

  Monitor Closely (1)ketoconazole 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 transdermal

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of buprenorphine transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• buprenorphine, long-acting injection

  Monitor Closely (1)ketoconazole 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

  Monitor Closely (1)ketoconazole will increase the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce starting dose of buspirone to 2.5 mg PO qDay. Adjust dose based on clinical assessment.

• busulfan

  Monitor Closely (1)ketoconazole will increase the level or effect of busulfan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• butabarbital

  Minor (2)butabarbital will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  butabarbital decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• butalbital

  Minor (2)butalbital will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• cabazitaxel

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of cabazitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, consider reducing the cabazitaxel dose by 25%.

• cabozantinib

  Serious - Use Alternative (1)ketoconazole 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.

• caffeine

  Minor (1)ketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• calcifediol

  Monitor Closely (1)ketoconazole, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

• calcitriol

  Monitor Closely (1)ketoconazole will increase the level or effect of calcitriol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• calcium carbonate

  Monitor Closely (1)calcium carbonate decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.Serious - Use Alternative (1)calcium carbonate will decrease the level or effect of ketoconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

• cannabidiol

  Monitor Closely (1)ketoconazole will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

• capmatinib

  Monitor Closely (1)ketoconazole will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• carbamazepine

  Monitor Closely (1)carbamazepine will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid combination for 2 weeks before and during ketoconazole use if possible. Monitor plasma levels when used concomitantly.

• cariprazine

  Monitor Closely (1)ketoconazole 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.

• carvedilol

  Monitor Closely (1)ketoconazole will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• celecoxib

  Minor (1)ketoconazole will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ceritinib

  Monitor Closely (1)ketoconazole increases levels of ceritinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole 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.

• cevimeline

  Monitor Closely (1)ketoconazole will increase the level or effect of cevimeline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• chlordiazepoxide

  Monitor Closely (1)ketoconazole will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)ketoconazole increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

• chlorpromazine

  Serious - Use Alternative (1)chlorpromazine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• chlorpropamide

  Monitor Closely (1)ketoconazole increases levels of chlorpropamide by decreasing metabolism. Use Caution/Monitor.

• cholic acid

  Monitor Closely (1)ketoconazole increases toxicity of cholic acid by decreasing elimination. Modify Therapy/Monitor Closely. Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP). May exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. If concomitant use is necessary, monitor serum transaminases and bilirubin.

• ciclesonide inhaled

  Monitor Closely (2)ketoconazole increases levels of ciclesonide inhaled by decreasing metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of ciclesonide inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cilostazol

  Monitor Closely (1)ketoconazole increases toxicity of cilostazol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider decreasing cilostazol dose; moderate CYP2C19 inhibitors may increase serum levels of 3,4-dehydrocilostazol (active metabolite); dose reduction to 50 mg twice daily should be considered.Serious - Use Alternative (1)ketoconazole will increase the level or effect of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Dose reduction to 50 mg twice daily should be considered

• cimetidine

  Monitor Closely (1)cimetidine will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)cimetidine will decrease the level or effect of ketoconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

• cinacalcet

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of cinacalcet by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• clarithromycin

  Monitor Closely (1)clarithromycin will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (2)clarithromycin and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.
  
  ketoconazole will increase the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• clobazam

  Monitor Closely (1)ketoconazole will increase the level or effect of clobazam by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Dosage adjustment may be required; CYP2C19 inhibitors may result in increased exposure to N-desmethylclobazam (active metabolite).

• clomipramine

  Monitor Closely (1)ketoconazole will increase the level or effect of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)clomipramine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• clonazepam

  Monitor Closely (1)ketoconazole will increase the level or effect of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• clopidogrel

  Monitor Closely (1)ketoconazole decreases effects of clopidogrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clopidogrel efficacy may be reduced by drugs that inhibit CYP3A4. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. Clopidogrel is metabolized to this active metabolite in part by CYP3A4. .Serious - Use Alternative (1)ketoconazole decreases effects of clopidogrel by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug. Clopidogrel efficacy may be reduced by drugs that inhibit CYP2C19. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. Clopidogrel is metabolized to this active metabolite in part by CYP2C19. .

• clorazepate

  Monitor Closely (1)ketoconazole will increase the level or effect of clorazepate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• clozapine

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• cobicistat

  Monitor Closely (1)cobicistat, ketoconazole. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Specific dosage recommendations for ketoconazole are not available when coadministered with cobicistat.Serious - Use Alternative (1)ketoconazole will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• cobimetinib

  Serious - Use Alternative (1)ketoconazole 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).

• codeine

  Monitor Closely (1)ketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• colchicine

  Serious - Use Alternative (1)ketoconazole 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.

• conivaptan

  Contraindicated (1)ketoconazole will increase the level or effect of conivaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of conivaptan with strong CYP3A4 inhibitors is contraindicated.Minor (1)conivaptan will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• conjugated estrogens

  Monitor Closely (2)ketoconazole will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• conjugated estrogens, vaginal

  Monitor Closely (1)ketoconazole will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• copanlisib

  Serious - Use Alternative (1)ketoconazole 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.

• cortisone

  Monitor Closely (1)ketoconazole will increase the level or effect of cortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole will increase the level or effect of cortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)cortisone will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• crizotinib

  Serious - Use Alternative (1)ketoconazole increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. See prescribing information for precise dosage modification.

• cyclophosphamide

  Monitor Closely (1)ketoconazole increases toxicity of cyclophosphamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cyclosporine

  Monitor Closely (1)ketoconazole will increase the level or effect of cyclosporine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• dabigatran

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Atrial fibrillation: Decrease dabigatran dose when coadministered with ketoconazole if CrCl is 30-50 mL/min. Avoid coadministering dabigatran with ketoconazole if CrCl <30 mL/min. DVT/PE treatment: Avoid coadministering dabigatran with ketoconazole if CrCl <50 mL/min

• dabrafenib

  Serious - Use Alternative (1)ketoconazole increases levels of dabrafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dapsone

  Monitor Closely (1)ketoconazole will increase the level or effect of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• daridorexant

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• darifenacin

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)darifenacin will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• darolutamide

  Monitor Closely (1)ketoconazole 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

  Serious - Use Alternative (1)ketoconazole, darunavir. Either increases effects of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Specific dosage recommendations for ketoconazole are not available when coadministered with darunavir. .

• dasatinib

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of dasatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)dasatinib will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• daunorubicin

  Monitor Closely (1)ketoconazole will increase the level or effect of daunorubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• deferasirox

  Monitor Closely (1)deferasirox will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• deflazacort

  Monitor Closely (3)ketoconazole will increase the level or effect of deflazacort by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole and deflazacort both decrease serum potassium. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease deflazacort dose to one-third of the recommended dose if coadministered with moderate or strong CYP3A4 inhibitors.

• desipramine

  Serious - Use Alternative (1)desipramine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• desloratadine

  Minor (1)ketoconazole increases levels of desloratadine by decreasing metabolism. Minor/Significance Unknown.

• dexamethasone

  Monitor Closely (1)ketoconazole will increase the level or effect of dexamethasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole will increase the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)dexamethasone will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dexlansoprazole

  Serious - Use Alternative (1)dexlansoprazole will decrease the level or effect of ketoconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

• DHEA, herbal

  Minor (1)DHEA, herbal will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• diazepam

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• diazepam intranasal

  Monitor Closely (2)ketoconazole will increase the level or effect of diazepam intranasal by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Strong or moderate CYP2C19 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.
  
  ketoconazole 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.

• diclofenac

  Monitor Closely (1)ketoconazole will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Do not exceed diclofenac dose of 50 mg BID

• didanosine

  Monitor Closely (1)didanosine will decrease the level or effect of ketoconazole 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

  Monitor Closely (1)ketoconazole 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

  Monitor Closely (1)ketoconazole will increase the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• dihydroergotamine

  Contraindicated (1)ketoconazole will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• dihydroergotamine intranasal

  Contraindicated (1)ketoconazole will increase the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• diltiazem

  Monitor Closely (2)diltiazem will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of diltiazem and ketoconazole may increase both drug levels, toxities, and additive negative inotropic effects.
  
  ketoconazole will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• disopyramide

  Contraindicated (2)ketoconazole will increase the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  disopyramide and ketoconazole both increase QTc interval. Contraindicated.

• docetaxel

  Monitor Closely (2)ketoconazole will increase the level or effect of docetaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dofetilide

  Serious - Use Alternative (1)dofetilide and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• dolasetron

  Monitor Closely (1)dolasetron and ketoconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• donepezil

  Monitor Closely (1)ketoconazole will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• doravirine

  Minor (1)ketoconazole will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

• doxepin

  Serious - Use Alternative (1)doxepin and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• doxorubicin

  Monitor Closely (2)ketoconazole will increase the level or effect of doxorubicin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of doxorubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• doxorubicin liposomal

  Monitor Closely (2)ketoconazole will increase the level or effect of doxorubicin liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of doxorubicin liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• dronabinol

  Monitor Closely (2)ketoconazole will increase the level or effect of dronabinol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Dronabinol is a CYP2C9 substrate.
  
  ketoconazole will increase the level or effect of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dronabinol is a CYP3A4 substrate.

• dronedarone

  Contraindicated (2)ketoconazole will increase the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  dronedarone and ketoconazole both increase QTc interval. Contraindicated.

• droperidol

  Serious - Use Alternative (1)droperidol and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• dutasteride

  Monitor Closely (1)ketoconazole will increase the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• duvelisib

  Monitor Closely (3)ketoconazole will increase the level or effect of duvelisib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of duvelisib by Other (see comment). Use Caution/Monitor. Coadministration of duvelisib (a BCRP substrate) with a BCRP transport inhibitor may increase levels or effects of duvelisib.
  
  ketoconazole 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.

• edoxaban

  Serious - Use Alternative (1)ketoconazole 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

  Monitor Closely (1)ketoconazole will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)efavirenz will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• elacestrant

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• elagolix

  Monitor Closely (1)ketoconazole 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.

• elbasvir/grazoprevir

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of elbasvir/grazoprevir with certain strong CYP3A4 inhibitors

• eletriptan

  Serious - Use Alternative (1)ketoconazole increases levels of eletriptan by decreasing metabolism. Contraindicated. Separate by 72 hours.

• eliglustat

  Contraindicated (2)ketoconazole 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
  
  ketoconazole increases levels of eliglustat by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated. If coadministered with strong or moderate CYP2D6 inhibitors, reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive and intermediate metabolizers; eliglustat is contraindiated if strong or moderate CYP2D6 inhibitors are given concomitantly with strong or moderate CYP3A inhibitors.

• eluxadoline

  Monitor Closely (1)ketoconazole increases levels of eluxadoline by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. As a precautionary measure due to incomplete information on the metabolism of eluxadoline, use caution when coadministered with strong CYP2C9/10 inhibitors.Serious - Use Alternative (1)ketoconazole increases levels of eluxadoline by decreasing metabolism. Avoid or Use Alternate Drug. Decrease eluxadoline dose to 75 mg PO BID if coadministered with OATP1B1 inhibitors. .

• elvitegravir

  Monitor Closely (1)ketoconazole, elvitegravir. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministered, do not exceed ketoconazole 200 mg/day; no dose adjustment needed for elvitegravir.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (2)elvitegravir/cobicistat/emtricitabine/tenofovir DF, ketoconazole. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Both cobicistat and ketoconazole are CYP3A4 inhibitors; do not exceed ketoconazole dose of 200 mg/day.
  
  ketoconazole will increase the level or effect of elvitegravir/cobicistat/emtricitabine/tenofovir DF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit ketoconazole to 200 mg/day when administered with elvitegravir/cobicistat/emtricitabine/tenofovir DF.

• encorafenib

  Monitor Closely (1)encorafenib, ketoconazole. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.Serious - Use Alternative (1)ketoconazole will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, reduce encorafenib dose to 150 mg/day if current dose is 450 mg/day and 75 mg/day if current dose is 150-300mg/day. After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

• enfortumab vedotin

  Monitor Closely (2)ketoconazole 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.
  
  ketoconazole will increase the level or effect of enfortumab vedotin by Other (see comment). Use Caution/Monitor. Coadministration with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE) exposure, which may increase the risk of enfortumab vedotin toxicities. Closely monitor for signs of toxicities.

• entrectinib

  Serious - Use Alternative (1)ketoconazole 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

  Serious - Use Alternative (1)enzalutamide will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ketoconazole with strong CYP3A4 inducers from 2 weeks and during treatment with ketoconazole tablets. If use is unavoidable, monitor antifungal activity and increase ketoconazole if necessary.

• epinephrine

  Serious - Use Alternative (1)epinephrine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• epinephrine racemic

  Serious - Use Alternative (1)epinephrine racemic and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• eplerenone

  Monitor Closely (1)ketoconazole will increase the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole increases levels of eplerenone by decreasing metabolism. Contraindicated.

• erdafitinib

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of erdafitinib by altering metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration with strong CYP3A4/CYP2C9 inhibitors, monitor closely for adverse reactions and consider decreasing dose accordingly. If strong CYP3A4/CYP2C9 inhibitor is discontinued, consider increasing erdafitinib dose in the absence of any drug-related toxicities.

• ergoloid mesylates

  Contraindicated (1)ketoconazole will increase the level or effect of ergoloid mesylates by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• ergonovine

  Contraindicated (1)ketoconazole will increase the level or effect of ergonovine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• ergotamine

  Contraindicated (1)ketoconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• erlotinib

  Serious - Use Alternative (2)ketoconazole will increase the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, monitor for erlotinib toxicities. If severe toxicities do occur, reduce erlotinib dose in 50-mg decrements.
  
  ketoconazole will increase the level or effect of erlotinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• erythromycin base

  Monitor Closely (2)ketoconazole will increase the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  erythromycin base will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)erythromycin base and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  Monitor Closely (2)ketoconazole will increase the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  erythromycin ethylsuccinate will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)erythromycin ethylsuccinate and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  Monitor Closely (2)ketoconazole will increase the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  erythromycin lactobionate will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)erythromycin lactobionate and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin stearate

  Monitor Closely (2)ketoconazole will increase the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  erythromycin stearate will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)erythromycin stearate and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• eslicarbazepine acetate

  Minor (1)eslicarbazepine acetate will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• esomeprazole

  Serious - Use Alternative (1)esomeprazole will decrease the level or effect of ketoconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

• estradiol

  Monitor Closely (2)ketoconazole will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• estradiol vaginal

  Monitor Closely (1)ketoconazole 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

  Monitor Closely (2)ketoconazole will increase the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of estrogens conjugated synthetic by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• estrogens esterified

  Monitor Closely (1)ketoconazole will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estropipate

  Monitor Closely (2)ketoconazole will increase the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of estropipate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• eszopiclone

  Monitor Closely (1)ketoconazole will increase the level or effect of eszopiclone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Eszopiclone dose should not exceed 2 mg/day when coadministered with strong CYP3A4 inhibitors.

• ethinylestradiol

  Monitor Closely (1)ketoconazole will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inhibitors such as ketoconazole may increase plasma hormone levels.

• ethosuximide

  Monitor Closely (1)ketoconazole will increase the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ethotoin

  Monitor Closely (1)ketoconazole will increase the level or effect of ethotoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• etonogestrel

  Monitor Closely (1)ketoconazole will increase the level or effect of etonogestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• etoposide

  Monitor Closely (2)ketoconazole will increase the level or effect of etoposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of etoposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• etravirine

  Monitor Closely (2)ketoconazole will increase the level or effect of etravirine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  ketoconazole, etravirine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Ketoconazole, a CYP3A4 inhibitor and substrate, may increase plasma concentrations of etravirine. Etravirine may decrease ketoconazole plasma concentrations. Consider dose adjustment of ketoconazole depending on the other coadministered drugs.Minor (1)etravirine will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• eucalyptus

  Monitor Closely (1)ketoconazole will increase the level or effect of eucalyptus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• everolimus

  Serious - Use Alternative (2)ketoconazole will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  ketoconazole will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• famotidine

  Serious - Use Alternative (1)famotidine will decrease the level or effect of ketoconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

• fedratinib

  Serious - Use Alternative (2)ketoconazole 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.
  
  ketoconazole will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

• felbamate

  Monitor Closely (1)ketoconazole will increase the level or effect of felbamate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• felodipine

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fentanyl

  Monitor Closely (1)ketoconazole will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fentanyl intranasal

  Monitor Closely (1)ketoconazole will increase the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fentanyl transdermal

  Monitor Closely (1)ketoconazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fentanyl transmucosal

  Monitor Closely (1)ketoconazole will increase the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fesoterodine

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of fesoterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fexinidazole

  Serious - Use Alternative (1)ketoconazole 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.

• fexofenadine

  Minor (1)ketoconazole will increase the level or effect of fexofenadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• finasteride

  Monitor Closely (1)ketoconazole will increase the level or effect of finasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• finerenone

  Contraindicated (1)ketoconazole will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• fingolimod

  Monitor Closely (1)ketoconazole increases levels of fingolimod by Other (see comment). Use Caution/Monitor. Comment: Mechanism: affecting hepatic enzyme CYP4F2 metabolism Monitor for adverse events of fingolimod when concomitantly used with ketoconazole.

• flecainide

  Monitor Closely (1)flecainide and ketoconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• flibanserin

  Contraindicated (1)ketoconazole 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.

• fluconazole

  Serious - Use Alternative (1)fluconazole and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)fluconazole will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fludrocortisone

  Monitor Closely (2)ketoconazole will increase the level or effect of fludrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of fludrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)fludrocortisone will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• flunisolide inhaled

  Monitor Closely (1)ketoconazole will increase the level or effect of flunisolide inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fluoxetine

  Monitor Closely (1)fluoxetine and ketoconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• fluphenazine

  Serious - Use Alternative (1)fluphenazine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• flurazepam

  Monitor Closely (1)ketoconazole will increase the level or effect of flurazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• flurbiprofen

  Minor (1)ketoconazole will increase the level or effect of flurbiprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fluticasone furoate

  Monitor Closely (1)ketoconazole will increase the level or effect of fluticasone furoate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inhibitors may increase fluticasone systemic exposure

• fluticasone inhaled

  Monitor Closely (1)ketoconazole 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

• fluticasone intranasal

  Serious - Use Alternative (1)ketoconazole 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.

• fluvastatin

  Monitor Closely (1)ketoconazole increases toxicity of fluvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.Minor (1)ketoconazole will increase the level or effect of fluvastatin by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fluvoxamine

  Monitor Closely (1)fluvoxamine and ketoconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• formoterol

  Serious - Use Alternative (1)formoterol and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• fosamprenavir

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of fosamprenavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Dose reduction of ketoconazole may be needed for patients receiving >400 mg ketoconazole day. When coadministered with fosamprenavir with ritonavir, ketoconazole doses (>200 mg/day) are not recommended.Minor (1)fosamprenavir will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fosaprepitant

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of fosaprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)fosaprepitant will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• foscarnet

  Monitor Closely (1)foscarnet and ketoconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• fosphenytoin

  Monitor Closely (1)ketoconazole will increase the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (1)fosphenytoin will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fostamatinib

  Monitor Closely (1)ketoconazole will increase the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors may increase exposure to R406 (fostamatinib major active metabolite). Monitor for toxicities that may require fostamatinib dose reduction.

• futibatinib

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inhibitors may increase incidence/severity of futibatinib toxicities.

• galantamine

  Monitor Closely (1)ketoconazole will increase the level or effect of galantamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ganaxolone

  Minor (1)ketoconazole, ganaxolone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Changes in ganaxolone exposures when coadministered with strong, moderate, or weak CYP3A4 inhibitors are not expected to be clinically significant.

• gefitinib

  Monitor Closely (1)ketoconazole 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.

• gentamicin

  Monitor Closely (1)ketoconazole will increase the level or effect of gentamicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)ketoconazole decreases levels of gentamicin by unknown mechanism. Minor/Significance Unknown.

• gilteritinib

  Serious - Use Alternative (1)ketoconazole 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. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.

• glasdegib

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of glasdegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternate therapies that are not strong CYP3A inhibitors or monitor for increased risk of adverse effects, including QTc interval prolongation.

• glecaprevir/pibrentasvir

  Monitor Closely (1)ketoconazole will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• glimepiride

  Monitor Closely (1)ketoconazole increases levels of glimepiride by decreasing metabolism. Use Caution/Monitor.

• glipizide

  Monitor Closely (1)ketoconazole increases levels of glipizide by decreasing metabolism. Use Caution/Monitor.

• glyburide

  Monitor Closely (2)ketoconazole increases levels of glyburide by decreasing metabolism. Use Caution/Monitor.
  
  ketoconazole increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

• grapefruit

  Monitor Closely (1)grapefruit decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.Minor (1)grapefruit will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• griseofulvin

  Minor (1)griseofulvin will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• guanfacine

  Monitor Closely (1)ketoconazole will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inhibitors significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if coadministered, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available.

• haloperidol

  Monitor Closely (1)ketoconazole will increase the level or effect of haloperidol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)haloperidol and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• hydrocodone

  Monitor Closely (1)ketoconazole will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

• hydrocortisone

  Monitor Closely (2)ketoconazole will increase the level or effect of hydrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of hydrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)hydrocortisone will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• hydroxyprogesterone caproate (DSC)

  Monitor Closely (1)ketoconazole will increase the level or effect of hydroxyprogesterone caproate (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ibrutinib

  Serious - Use Alternative (1)ketoconazole 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

  Minor (1)ketoconazole will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ibuprofen IV

  Minor (1)ketoconazole will increase the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ibuprofen/famotidine

  Serious - Use Alternative (1)ibuprofen/famotidine will decrease the level or effect of ketoconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

• ibutilide

  Contraindicated (1)ibutilide and ketoconazole both increase QTc interval. Contraindicated.

• idelalisib

  Serious - Use Alternative (1)ketoconazole 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

• ifosfamide

  Monitor Closely (1)ketoconazole 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

  Monitor Closely (1)iloperidone and ketoconazole both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)ketoconazole will increase the level or effect of iloperidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• imatinib

  Monitor Closely (2)ketoconazole will increase the level or effect of imatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• imipramine

  Monitor Closely (1)ketoconazole will increase the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)imipramine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• indacaterol, inhaled

  Monitor Closely (1)ketoconazole increases levels of indacaterol, inhaled by Other (see comment). Use Caution/Monitor. 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.

• indapamide

  Contraindicated (1)indapamide and ketoconazole both increase QTc interval. Contraindicated.

• indinavir

  Monitor Closely (2)ketoconazole will increase the level or effect of indinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole 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 PO q8hr when administering ketoconazole concurrently.Minor (1)indinavir will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• infigratinib

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• irinotecan

  Monitor Closely (1)ketoconazole will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (2)ketoconazole will increase the level or effect of irinotecan by decreasing metabolism. Avoid or Use Alternate Drug. UGT1A1 inhibitors decrease irinotecan metabolism
  
  ketoconazole will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• irinotecan liposomal

  Monitor Closely (1)ketoconazole will increase the level or effect of irinotecan liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (2)ketoconazole will increase the level or effect of irinotecan liposomal by decreasing metabolism. Avoid or Use Alternate Drug. UGT1A1 inhibitors decrease irinotecan metabolism
  
  ketoconazole will increase the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. UGT1A1 inhibitors decrease irinotecan metabolism

• isavuconazonium sulfate

  Contraindicated (1)ketoconazole will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• isoniazid

  Contraindicated (1)isoniazid decreases levels of ketoconazole by unspecified interaction mechanism. Contraindicated.Minor (1)isoniazid will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• isradipine

  Monitor Closely (1)ketoconazole will increase the level or effect of isradipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• istradefylline

  Monitor Closely (1)ketoconazole 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.

• itraconazole

  Monitor Closely (1)ketoconazole will increase the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (2)ketoconazole will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  itraconazole will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ivabradine

  Contraindicated (1)ketoconazole will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.

• ivacaftor

  Monitor Closely (1)ketoconazole 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

  Monitor Closely (1)ketoconazole will increase the level or effect of ivermectin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• ivosidenib

  Serious - Use Alternative (2)ketoconazole will increase the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with ivosidenib or replace with alternate therapies. 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 the recommended dose of 500 mg qDay. Monitor for increased risk of QTc interval prolongation.
  
  ivosidenib will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• ixabepilone

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lacosamide

  Monitor Closely (2)ketoconazole increases levels of lacosamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients with renal or hepatic impairment who are taking strong CYP3A4 and CYP2C9 inhibitors may have a significant increase in exposure to lacosamide. Dose reduction may be necessary in these patients.
  
  ketoconazole increases levels of lacosamide by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Patients with renal or hepatic impairment who are taking strong CYP3A4 and CYP2C9 inhibitors may have a significant increase in exposure to lacosamide. Dose reduction may be necessary in these patients.

• lansoprazole

  Monitor Closely (1)ketoconazole will increase the level or effect of lansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)lansoprazole will decrease the level or effect of ketoconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

• lapatinib

  Monitor Closely (2)ketoconazole will increase the level or effect of lapatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole and lapatinib both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)ketoconazole will increase the level or effect of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)lapatinib will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• larotrectinib

  Serious - Use Alternative (1)ketoconazole 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

  Serious - Use Alternative (1)ketoconazole 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.

• lemborexant

  Serious - Use Alternative (1)ketoconazole 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.

• lenacapavir

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of lenacapavir by Other (see comment). Avoid or Use Alternate Drug. Drugs that inhibit P-gp, UGT1A1, and strongly inhibit CYP3A may significantly increase lenacapavir plasma concentrations.

• leniolisib

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of leniolisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lesinurad

  Monitor Closely (1)ketoconazole will increase the level or effect of lesinurad by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• letermovir

  Monitor Closely (2)ketoconazole increases effects of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.
  
  letermovir increases levels of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levamlodipine

  Monitor Closely (1)ketoconazole 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.

• levofloxacin

  Monitor Closely (1)ketoconazole and levofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

• levomilnacipran

  Monitor Closely (1)ketoconazole 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

  Monitor Closely (1)ketoconazole 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

  Monitor Closely (1)ketoconazole will increase the level or effect of linagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lofepramine

  Serious - Use Alternative (1)lofepramine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• lomitapide

  Contraindicated (1)ketoconazole increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increases lomitapide levels several folds.

• lonafarnib

  Contraindicated (1)ketoconazole 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.

• loperamide

  Monitor Closely (1)ketoconazole will increase the level or effect of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• lopinavir

  Monitor Closely (1)ketoconazole will increase the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Ketoconazole doses > 200 mg/day is not recommended when concurrently used with lopinavir/ritonavir.

• loratadine

  Monitor Closely (1)ketoconazole will increase the level or effect of loratadine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)ketoconazole will increase the level or effect of loratadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• lorlatinib

  Serious - Use Alternative (1)ketoconazole 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.

• losartan

  Monitor Closely (1)ketoconazole will increase the level or effect of losartan by affecting hepatic enzyme CYP2C9/10 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.Minor (1)ketoconazole decreases effects of losartan by decreasing metabolism. Minor/Significance Unknown. 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.

• lovastatin

  Contraindicated (1)ketoconazole will increase the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors increase systemic statin exposure and risk of myopathy, including rhabdomyolysisMonitor Closely (1)ketoconazole will increase the level or effect of lovastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• lumacaftor/ivacaftor

  Monitor Closely (1)ketoconazole 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.Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lumateperone

  Monitor Closely (1)ketoconazole will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 10.5 mg/day if coadministered with strong CYP3A4 inhibitors.

• lumefantrine

  Serious - Use Alternative (2)ketoconazole and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.
  
  ketoconazole will increase the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)lumefantrine will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lurasidone

  Contraindicated (1)ketoconazole 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.

• lurbinectedin

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce lurbinectedin dose by 50%. After strong CYP3A inhibitor discontinued for 5 half-lives, increase lurbinectedin to dose used before coadministration.

• macimorelin

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of macimorelin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• macitentan

  Serious - Use Alternative (1)ketoconazole 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

  Serious - Use Alternative (1)maprotiline and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• maraviroc

  Monitor Closely (2)ketoconazole will increase the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decrease maraviroc dose to 150 mg BID when coadministered with strong CYP3A4 inhibitors. Refer to prescribing for pediatric dosage modifications.
  
  ketoconazole will increase the level or effect of maraviroc by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• marijuana

  Monitor Closely (1)ketoconazole will increase the level or effect of marijuana by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)marijuana will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• mavacamten

  Contraindicated (2)ketoconazole will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.
  
  ketoconazole will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

• medroxyprogesterone

  Monitor Closely (1)ketoconazole will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• mefloquine

  Serious - Use Alternative (2)mefloquine increases toxicity of ketoconazole by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.
  
  ketoconazole 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.

• meloxicam

  Minor (1)ketoconazole will increase the level or effect of meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• mestranol

  Monitor Closely (1)ketoconazole will increase the level or effect of mestranol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole will increase the level or effect of mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)ketoconazole decreases effects of mestranol by increasing metabolism. Minor/Significance Unknown. May also cause menstrual irregularities.

• methadone

  Contraindicated (2)ketoconazole will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  ketoconazole and methadone both increase QTc interval. Contraindicated.

• methylergonovine

  Contraindicated (1)ketoconazole will increase the level or effect of methylergonovine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• methylprednisolone

  Monitor Closely (1)ketoconazole will increase the level or effect of methylprednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole will increase the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)methylprednisolone will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• metronidazole

  Minor (1)metronidazole will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• miconazole vaginal

  Minor (1)miconazole vaginal will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• midazolam

  Serious - Use Alternative (2)ketoconazole increases levels of midazolam by decreasing metabolism. Contraindicated.
  
  ketoconazole will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• midazolam intranasal

  Serious - Use Alternative (1)ketoconazole 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

  Serious - Use Alternative (1)ketoconazole 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

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of mifepristone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• mipomersen

  Monitor Closely (1)mipomersen, ketoconazole. 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

  Monitor Closely (1)ketoconazole will increase the level or effect of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce mirtazapine dose if coadministration of strong CYP3A4 inhibitor is necessary. Once CYP3A4 inhibitor is discontinued, consider increasing mirtazapine dose.

• mirvetuximab soravtansine

  Monitor Closely (1)ketoconazole will increase the level or effect of mirvetuximab soravtansine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with strong CYP3A4 inhibitors may increase unconjugated DM4 (a CYP3A4 substrate and the cytotoxic component of the antibody drug conjugate for mirvetuximab soravtansine) exposure, which may increase the risk of adverse reactions.

• mizolastine

  Serious - Use Alternative (1)ketoconazole increases levels of mizolastine by decreasing metabolism. Contraindicated.

• mobocertinib

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• modafinil

  Monitor Closely (1)ketoconazole will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• mometasone inhaled

  Monitor Closely (1)ketoconazole will increase the level or effect of mometasone inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increases riak for systemic corticosteroid side effects

• mometasone, intranasal

  Monitor Closely (1)ketoconazole will increase the level or effect of mometasone, intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• montelukast

  Monitor Closely (1)ketoconazole will increase the level or effect of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• moxifloxacin

  Serious - Use Alternative (1)ketoconazole and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• nafcillin

  Minor (1)nafcillin will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• naldemedine

  Monitor Closely (2)ketoconazole 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.
  
  ketoconazole 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.

• naloxegol

  Contraindicated (1)ketoconazole 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

• nateglinide

  Monitor Closely (1)ketoconazole will increase the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• nefazodone

  Monitor Closely (2)nefazodone will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of nefazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nelfinavir

  Monitor Closely (2)ketoconazole will increase the level or effect of nelfinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)nelfinavir will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• neomycin PO

  Monitor Closely (1)ketoconazole will increase the level or effect of neomycin PO by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)ketoconazole decreases levels of neomycin PO by unknown mechanism. Minor/Significance Unknown.

• neratinib

  Serious - Use Alternative (1)ketoconazole 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.

• netupitant/palonosetron

  Monitor Closely (1)ketoconazole 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

• nevirapine

  Serious - Use Alternative (2)ketoconazole will increase the level or effect of nevirapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  nevirapine decreases levels of ketoconazole by increasing metabolism. Contraindicated.Minor (1)nevirapine will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nicardipine

  Monitor Closely (1)ketoconazole will increase the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nifedipine

  Monitor Closely (2)ketoconazole increases levels of nifedipine by decreasing metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)nifedipine will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nilotinib

  Monitor Closely (1)ketoconazole will increase the level or effect of nilotinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (2)ketoconazole and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.
  
  ketoconazole will increase the level or effect of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is avoidable, reduce nilotinib dosage to 300 mg PO qDay (resistant or intolerant Ph+ CML patients) or to 200 mg PO qDay (newly diagnosed Ph+ CML-CP patients). If strong inhibitor is discontinued, allow a washout period before adjusting nilotinib dose upward to indicated dose. Monitor closely for QT prolongation.Minor (1)nilotinib will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nimodipine

  Monitor Closely (1)ketoconazole will increase the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nintedanib

  Monitor Closely (1)ketoconazole 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 .

• nirmatrelvir

  Monitor Closely (1)nirmatrelvir will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit ketoconazole adult dose to 200 mg/day if coadministered with ritonavir.

• nirmatrelvir/ritonavir

  Monitor Closely (1)nirmatrelvir/ritonavir will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit ketoconazole adult dose to 200 mg/day if coadministered with ritonavir.

• nisoldipine

  Contraindicated (1)ketoconazole will decrease the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• nitrendipine

  Monitor Closely (1)ketoconazole will increase the level or effect of nitrendipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nizatidine

  Serious - Use Alternative (1)nizatidine will decrease the level or effect of ketoconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

• norgestrel

  Monitor Closely (1)ketoconazole will increase the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may increase systemic concentration of norgestrel, which may increase risk for adverse effects

• nortriptyline

  Serious - Use Alternative (1)nortriptyline and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• octreotide

  Serious - Use Alternative (1)ketoconazole and octreotide both increase QTc interval. Avoid or Use Alternate Drug.

• octreotide (Antidote)

  Serious - Use Alternative (1)ketoconazole and octreotide (Antidote) both increase QTc interval. Avoid or Use Alternate Drug.

• ofloxacin

  Monitor Closely (1)ketoconazole and ofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

• olaparib

  Serious - Use Alternative (1)ketoconazole 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 100 mg PO BID.

• oliceridine

  Monitor Closely (2)ketoconazole will increase the level or effect of oliceridine by affecting hepatic enzyme CYP2D6 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.
  
  ketoconazole 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.

• omaveloxolone

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unavoidable, reduce omaveloxolone dose to 50 mg/day. Closely monitor and discontinue if adverse effects emerge.

• omeprazole

  Serious - Use Alternative (1)omeprazole will decrease the level or effect of ketoconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

• ondansetron

  Monitor Closely (1)ketoconazole will increase the level or effect of ondansetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP-450 inhibitors may decrease clearance of ondansetron. However, no dosage adjustment for ondansetron is recommended

• osilodrostat

  Monitor Closely (1)ketoconazole 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.

• osimertinib

  Minor (1)ketoconazole will increase the level or effect of osimertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ospemifene

  Monitor Closely (2)ketoconazole increases levels of ospemifene by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  ketoconazole increases levels of ospemifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• oxcarbazepine

  Minor (1)oxcarbazepine will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• oxybutynin

  Monitor Closely (1)ketoconazole will increase the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• oxycodone

  Monitor Closely (1)ketoconazole 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.

• ozanimod

  Serious - Use Alternative (1)ketoconazole increases toxicity of ozanimod by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of ozanimod (a BCRP substrate) with BCRP inhibitors increases the exposure of the minor (RP101988, RP101075) and major active metabolites (CC112273, CC1084037) of ozanimod, which may increase the risk of ozanimod adverse reactions. .

• paclitaxel

  Monitor Closely (2)ketoconazole will increase the level or effect of paclitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• paclitaxel protein bound

  Monitor Closely (2)ketoconazole will increase the level or effect of paclitaxel protein bound by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• pacritinib

  Contraindicated (1)ketoconazole will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• palbociclib

  Serious - Use Alternative (1)ketoconazole 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.

• paliperidone

  Monitor Closely (2)ketoconazole will increase the level or effect of paliperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole and paliperidone both increase QTc interval. Modify Therapy/Monitor Closely.

• palovarotene

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of palovarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• panobinostat

  Monitor Closely (1)ketoconazole 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

  Serious - Use Alternative (1)pantoprazole will decrease the level or effect of ketoconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.Minor (2)ketoconazole will increase the level or effect of pantoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  ketoconazole will increase the level or effect of pantoprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• parecoxib

  Monitor Closely (2)ketoconazole will increase the level or effect of parecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of parecoxib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• paricalcitol

  Monitor Closely (1)ketoconazole will increase the level or effect of paricalcitol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• paromomycin

  Monitor Closely (1)ketoconazole will increase the level or effect of paromomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)ketoconazole decreases levels of paromomycin by unknown mechanism. Minor/Significance Unknown.

• paroxetine

  Monitor Closely (1)ketoconazole and paroxetine both increase QTc interval. Modify Therapy/Monitor Closely.

• pazopanib

  Monitor Closely (1)ketoconazole and pazopanib both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole will increase the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of pazopanib with strong CYP3A4 inhibitors if possible; if must coadminister, decrease pazopanib dose to 400 mg/day

• pemigatinib

  Serious - Use Alternative (1)ketoconazole 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.

• pentamidine

  Contraindicated (1)ketoconazole and pentamidine both increase QTc interval. Contraindicated.

• pentobarbital

  Minor (2)pentobarbital will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  pentobarbital decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• perampanel

  Monitor Closely (1)ketoconazole will increase the level or effect of perampanel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• perphenazine

  Serious - Use Alternative (1)perphenazine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• pexidartinib

  Serious - Use Alternative (3)ketoconazole 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.
  
  ketoconazole will increase the level or effect of pexidartinib by Other (see comment). Avoid or Use Alternate Drug. Pexdartinib is a UGTA4 substrate. Reduce pexdartinib dose if concomitant use of UGT inhibitors cannot be avoided (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pexidartinib dose.
  
  ketoconazole and pexidartinib both increase inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

• phenobarbital

  Minor (2)phenobarbital will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  phenobarbital decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• phenytoin

  Monitor Closely (1)ketoconazole will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (1)phenytoin will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pimavanserin

  Serious - Use Alternative (1)ketoconazole 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.

• pimozide

  Contraindicated (2)ketoconazole and pimozide both increase QTc interval. Contraindicated.
  
  ketoconazole increases levels of pimozide by decreasing metabolism. Contraindicated. Risk of QT interval prolongation.Monitor Closely (1)ketoconazole will increase the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• pioglitazone

  Monitor Closely (1)ketoconazole will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• piroxicam

  Minor (1)ketoconazole will increase the level or effect of piroxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• pirtobrutinib

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.

• pitavastatin

  Monitor Closely (1)ketoconazole increases toxicity of pitavastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• polatuzumab vedotin

  Monitor Closely (1)ketoconazole 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.

• pomalidomide

  Serious - Use Alternative (2)ketoconazole increases levels of pomalidomide by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.
  
  ketoconazole increases levels of pomalidomide by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• ponatinib

  Serious - Use Alternative (1)ketoconazole increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.

• posaconazole

  Monitor Closely (2)ketoconazole will increase the level or effect of posaconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)posaconazole will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pralsetinib

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid use with drugs that are both strong CYP3A4 and P-gp inhibitors when possible. If combined, reduce pralsetinib dose to 200 mg qDay (if current dose is 300-400 mg qDay) or 100 mg qDay ( if current dose is 200 mg qDay) After CYP3A4 and P-gp inhibitor has been discontinued for 3-5 elimination half-lives, resume pralsetinib at the dose taken before initiating the inhibitor.

• pravastatin

  Monitor Closely (1)ketoconazole increases toxicity of pravastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• praziquantel

  Monitor Closely (1)ketoconazole will increase the level or effect of praziquantel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• prednisolone

  Monitor Closely (2)ketoconazole will increase the level or effect of prednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of prednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• prednisone

  Monitor Closely (1)ketoconazole will increase the level or effect of prednisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole will increase the level or effect of prednisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)prednisone will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pretomanid

  Serious - Use Alternative (1)ketoconazole, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

• primidone

  Minor (2)primidone will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  primidone decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• procainamide

  Contraindicated (1)ketoconazole and procainamide both increase QTc interval. Contraindicated.

• prochlorperazine

  Serious - Use Alternative (1)prochlorperazine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• progesterone intravaginal gel

  Monitor Closely (1)ketoconazole will increase the level or effect of progesterone intravaginal gel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• progesterone micronized

  Monitor Closely (1)ketoconazole will increase the level or effect of progesterone micronized by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• progesterone, natural

  Monitor Closely (1)ketoconazole will increase the level or effect of progesterone, natural by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• promazine

  Serious - Use Alternative (1)promazine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• promethazine

  Serious - Use Alternative (1)promethazine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• propafenone

  Monitor Closely (1)ketoconazole will increase the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• protriptyline

  Serious - Use Alternative (1)protriptyline and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• quetiapine

  Monitor Closely (1)ketoconazole will increase the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce quetiapine dose to one sixth of the original dose when coadministered with a strong CYP3A4 inhibitor.

• quinidine

  Contraindicated (2)ketoconazole will increase the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  quinidine and ketoconazole both increase QTc interval. Contraindicated.

• quinine

  Monitor Closely (1)ketoconazole will increase the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quinupristin/dalfopristin

  Minor (1)quinupristin/dalfopristin will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• quizartinib

  Monitor Closely (1)ketoconazole will increase the level or effect of quizartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce quizartinib dosage to 26.5 mg qDay (if current dosage is 53 mg/day) or 17.7 mg qDay (if current dosage is 26.5 mg/day or 35.4 mg/day) when coadministered with strong CYP3A inhibitors. If current dosage is 17.7 mg qDay, interrupt quizartinib for the duration of strong CYP3A inhibitor use. After discontinuation of a strong CYP3A inhibitor for 5 half-lives, resume quizartinib dose that was taken before initiating the strong inhibitor.

• rabeprazole

  Monitor Closely (1)ketoconazole will increase the level or effect of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)rabeprazole will decrease the level or effect of ketoconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

• ramelteon

  Monitor Closely (1)ketoconazole will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)ketoconazole will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ranolazine

  Contraindicated (2)ketoconazole will increase the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  ketoconazole and ranolazine both increase QTc interval. Contraindicated.

• red yeast rice

  Serious - Use Alternative (1)ketoconazole 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

  Serious - Use Alternative (1)ketoconazole 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

• repaglinide

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ribociclib

  Serious - Use Alternative (3)ketoconazole increases toxicity of ribociclib by QTc interval. Avoid or Use Alternate Drug.
  
  ketoconazole, ribociclib. Either increases effects of the other 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.
  
  ribociclib will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifabutin

  Monitor Closely (2)rifabutin decreases levels of ketoconazole by increasing metabolism. Use Caution/Monitor.
  
  rifabutin will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole will increase the level or effect of rifabutin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)ketoconazole increases levels of rifabutin by decreasing metabolism. Minor/Significance Unknown.

• rifampin

  Monitor Closely (1)rifampin will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)ketoconazole decreases levels of rifampin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Only applies to oral preparations of both agents.

• rifapentine

  Minor (1)rifapentine will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• rifaximin

  Monitor Closely (1)ketoconazole increases levels of rifaximin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• rilpivirine

  Monitor Closely (1)ketoconazole 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.

• rimegepant

  Serious - Use Alternative (3)ketoconazole will increase the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  ketoconazole will increase the level or effect of rimegepant by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
  
  ketoconazole will increase the level or effect of rimegepant by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of rimegepant (a BCRP substrate) with inhibitors of BCRP.

• riociguat

  Monitor Closely (3)ketoconazole 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
  
  ketoconazole 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
  
  ketoconazole will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider a starting riociguat dose of 0.5 mg TID when initiating riociguat in patients receiving strong CYP and P-gp/BCRP inhibitors. Monitor for signs and symptoms of hypotension on initiation and on treatment with strong CYP and P-gp/BCRP inhibitors.

• ripretinib

  Monitor Closely (1)ketoconazole 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

  Monitor Closely (2)ketoconazole will increase the level or effect of risperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole and risperidone both increase QTc interval. Modify Therapy/Monitor Closely.

• ritonavir

  Monitor Closely (2)ketoconazole will increase the level or effect of ritonavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Ketoconazole dose is not to exceed 200 mg/day when concurrently used with ritonavir. Minor (1)ritonavir will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• rivaroxaban

  Serious - Use Alternative (1)ketoconazole increases levels of rivaroxaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. 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

  Monitor Closely (2)ketoconazole will increase the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole increases levels of roflumilast by Other (see comment). Modify Therapy/Monitor Closely. Comment: Coadministration with dual inhibitors of CYP3A4 and CYP1A2 may increase systemic exposure and result in increased adverse reactions.

• romidepsin

  Monitor Closely (3)ketoconazole will increase the level or effect of romidepsin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of romidepsin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely.

• rosuvastatin

  Serious - Use Alternative (1)ketoconazole increases toxicity of rosuvastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• rufinamide

  Minor (1)rufinamide will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ruxolitinib

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If starting ruxolitinib and currently treated with strong CYP3A4 inhibitors, start ruxolitinib at 5 mg BID in polycythemia vera. In myelofibrosis patients, start ruxolitinib at 10 mg BID in those with platelet counts 100 x10^9/L or greater, or 5 mg qDay in those with platelet counts at 50 to 100 x 10^9/L. In patients currently on ruxolitinib and starting a CYP3A4 inhibitor, reduce ruxolitinib dose by 50% (ie, 10 mg BID to 5 mg BID). Avoid strong CYP3A4 inhibitors in patients currently treated with ruxolitinib 5 mg qDay.

• ruxolitinib topical

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of ruxolitinib topical 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

  Serious - Use Alternative (1)ketoconazole decreases effects of Saccharomyces boulardii by unspecified interaction mechanism. Avoid or Use Alternate Drug. Systemic or oral antifungals may decrease activity of probiotic.

• sacubitril/valsartan

  Monitor Closely (1)ketoconazole will increase the level or effect of sacubitril/valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

• salmeterol

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of salmeterol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• saquinavir

  Monitor Closely (1)ketoconazole will increase the level or effect of saquinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole will increase the level or effect of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• saxagliptin

  Monitor Closely (1)ketoconazole 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

• secobarbital

  Minor (2)secobarbital will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  secobarbital decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• selexipag

  Monitor Closely (1)ketoconazole will increase the level or effect of selexipag by Other (see comment). Use Caution/Monitor. Selexipag is a ABCG2 (BCRP) substrate. Monitor selexipag for increased pharmacologic or adverse effects when coadministered with ABCG2 (BCRP) inhibitors.

• selpercatinib

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• selumetinib

  Serious - Use Alternative (1)ketoconazole 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.

• sildenafil

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP3A4 inhibitors and sildenafil (for pulmonary arterial hypertension) is not recommended. When used for erectile dysfunction, consider reducing initial sildenafil dose of 25 mg in patients also taking a strong CYP3A4 inhibitor and monitor for sildenafil toxicities (eg, dyspepsia, headache, hypotension).

• silodosin

  Contraindicated (1)ketoconazole will increase the level or effect of silodosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.Monitor Closely (1)ketoconazole will increase the level or effect of silodosin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• simvastatin

  Contraindicated (2)ketoconazole will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure
  
  ketoconazole increases toxicity of simvastatin by Other (see comment). Contraindicated. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• siponimod

  Serious - Use Alternative (2)ketoconazole will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.
  
  ketoconazole 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

  Contraindicated (1)ketoconazole increases levels of sirolimus by decreasing metabolism. Contraindicated.Monitor Closely (1)ketoconazole will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• sodium bicarbonate

  Monitor Closely (1)sodium bicarbonate decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.Serious - Use Alternative (1)sodium bicarbonate will decrease the level or effect of ketoconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

• sodium citrate/citric acid

  Monitor Closely (1)sodium citrate/citric acid decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.Serious - Use Alternative (1)sodium citrate/citric acid will decrease the level or effect of ketoconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

• sodium sulfate/?magnesium sulfate/potassium chloride

  Monitor Closely (1)sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of ketoconazole by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol

  Monitor Closely (1)ketoconazole and sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol both decrease serum potassium. Modify Therapy/Monitor Closely.

• sodium sulfate/potassium sulfate/magnesium sulfate

  Monitor Closely (1)sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of ketoconazole by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• sodium zirconium cyclosilicate

  Monitor Closely (1)sodium zirconium cyclosilicate will decrease the level or effect of ketoconazole 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.

• solifenacin

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Do not exceed a 5 mg/day dosage of solifenacin when concomitantly used with strong CYP3A4 inhibitors.

• sonidegib

  Serious - Use Alternative (1)ketoconazole 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

  Minor (1)ketoconazole will increase the level or effect of sorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sotalol

  Contraindicated (1)ketoconazole and sotalol both increase QTc interval. Contraindicated.

• sparsentan

  Serious - Use Alternative (1)ketoconazole, sparsentan. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. If unavoidable, interrupt treatment with sparsentan. When resuming sparsentan, consider dose titration. .

• St John's Wort

  Monitor Closely (1)St John's Wort will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• stiripentol

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• streptomycin

  Monitor Closely (1)ketoconazole will increase the level or effect of streptomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)ketoconazole decreases levels of streptomycin by unknown mechanism. Minor/Significance Unknown.

• sucralfate

  Monitor Closely (1)sucralfate decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• sufentanil

  Monitor Closely (1)ketoconazole will increase the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• sufentanil SL

  Monitor Closely (1)ketoconazole will increase the level or effect of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider dosage reduction of sufentanil until stable drug effects are achieved. Monitor for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing sufentanil dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

• sulfamethoxazole

  Monitor Closely (1)sulfamethoxazole and ketoconazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)ketoconazole will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• sunitinib

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, consider reducing the sunitinib dose to a minimum dosage as 37.5 mg qDay (GIST and RCC), on a schedule of 4 weeks on treatment followed by 2 weeks off. For pNET patients, consider reducing to25 mg qDay.

• suvorexant

  Serious - Use Alternative (1)ketoconazole 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.

• tacrolimus

  Monitor Closely (1)ketoconazole will increase the level or effect of tacrolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tacrolimus ointment

  Monitor Closely (1)ketoconazole will increase the level or effect of tacrolimus ointment by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tadalafil

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP3A4 inhibitors may reduce tadalafil clearance increasing systemic exposure to tadalafil; significantly increased levels may result in significant adverse events including severe hypotension, syncope, visual changes, and priapism.

• talazoparib

  Monitor Closely (1)ketoconazole will increase the level or effect of talazoparib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Talazoparib is a P-glycoprotein (P-gp) substrate; coadministration with P-gp inhibitors may increase talazoparib systemic exposure.Serious - Use Alternative (1)ketoconazole will increase the level or effect of talazoparib by Other (see comment). Avoid or Use Alternate Drug. BCRP inhibitors may increase systemic exposure of talazoparib (a BCRP substrate). If coadministration cannot be avoided, monitor for potential adverse reactions.

• tamoxifen

  Monitor Closely (2)ketoconazole, tamoxifen. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. CYP2C9/10 inhibition decreases tamoxifen metabolism to active metabolites.
  
  ketoconazole, tamoxifen. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inhibition decreases metabolism of tamoxifen to N-desmethyl tamoxifen (active metabolite with similar biologic activity).

• tamsulosin

  Monitor Closely (1)ketoconazole increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole increases levels of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for increased toxicity.

• tasimelteon

  Monitor Closely (1)ketoconazole will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tazemetostat

  Serious - Use Alternative (1)ketoconazole 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.

• telavancin

  Monitor Closely (1)ketoconazole and telavancin both increase QTc interval. Modify Therapy/Monitor Closely.

• temsirolimus

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• teniposide

  Monitor Closely (1)ketoconazole will increase the level or effect of teniposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• terbinafine

  Monitor Closely (2)ketoconazole will increase the level or effect of terbinafine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  ketoconazole will decrease the level or effect of terbinafine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tezacaftor

  Monitor Closely (1)ketoconazole 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

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• thioridazine

  Serious - Use Alternative (1)thioridazine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• ticagrelor

  Serious - Use Alternative (1)ketoconazole increases levels of ticagrelor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Ticagrelor is metabolized by CYP3A4/5. Avoid use with strong CYP3A inhibitors.

• tinidazole

  Minor (1)ketoconazole will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• tipranavir

  Monitor Closely (1)ketoconazole will increase the level or effect of tipranavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Ketoconazole dose is not to exceed 200 mg/day when concurrently used.

• tisotumab vedotin

  Monitor Closely (1)ketoconazole increases levels of tisotumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tisotumab vedotin?s active metabolite (MMAE) is a CYP3A4 substrate. Coadministration with strong CYP3A4 inhibitors may increase unconjugated MMAE systemic exposure and increase risk of adverse effects.

• tobramycin

  Monitor Closely (1)ketoconazole will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)ketoconazole decreases levels of tobramycin by unknown mechanism. Minor/Significance Unknown.

• tofacitinib

  Serious - Use Alternative (1)ketoconazole increases levels of tofacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce tofacitinib dose to 5 mg qDay (psoriatic arthritis and rheumatoid arthritis) when coadministered with potent CYP3A4 inhibitors. Refer to prescribing information for other indications. .

• tolazamide

  Monitor Closely (1)ketoconazole increases levels of tolazamide by decreasing metabolism. Use Caution/Monitor.

• tolbutamide

  Monitor Closely (1)ketoconazole increases levels of tolbutamide by decreasing metabolism. Use Caution/Monitor.Minor (1)ketoconazole will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• tolterodine

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Do not exceed tolterodine dose of 2mg qDay when coadministered with strong CYP3A4 inhibitors.

• tolvaptan

  Monitor Closely (1)ketoconazole will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• topiramate

  Minor (1)topiramate will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• topotecan

  Serious - Use Alternative (1)ketoconazole 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

• toremifene

  Serious - Use Alternative (1)ketoconazole increases levels of toremifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Metabolism of toremifene may be inhibited by drugs known to inhibit CYP3A4 hepatic enzymes.

• trabectedin

  Serious - Use Alternative (1)ketoconazole 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

• tramadol

  Monitor Closely (1)ketoconazole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May require decreased tramadol dose or adjustment of dosing interval; increased risk for serious adverse events including seizures and serotonin syndrome

• trazodone

  Serious - Use Alternative (2)trazodone and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.
  
  ketoconazole will increase the level or effect of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tretinoin

  Monitor Closely (1)ketoconazole increases levels of tretinoin by decreasing metabolism. Use Caution/Monitor.

• tretinoin topical

  Minor (1)ketoconazole increases levels of tretinoin topical by decreasing metabolism. Minor/Significance Unknown.

• triamcinolone acetonide injectable suspension

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• triazolam

  Contraindicated (1)ketoconazole increases levels of triazolam by decreasing metabolism. Contraindicated.

• trifluoperazine

  Serious - Use Alternative (1)trifluoperazine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• trimethoprim

  Monitor Closely (1)ketoconazole and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• trimipramine

  Monitor Closely (1)ketoconazole will increase the level or effect of trimipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)trimipramine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• tropisetron

  Monitor Closely (1)ketoconazole and tropisetron both increase QTc interval. Modify Therapy/Monitor Closely.

• ubrogepant

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of ubrogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• ulipristal

  Contraindicated (1)ketoconazole will increase the level or effect of ulipristal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• umeclidinium bromide/vilanterol inhaled

  Monitor Closely (1)ketoconazole 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

  Monitor Closely (1)ketoconazole 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

  Monitor Closely (1)ketoconazole 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.

• valoctocogene roxaparvovec

  Monitor Closely (1)ketoconazole and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.

• valsartan

  Monitor Closely (1)ketoconazole will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

• vandetanib

  Monitor Closely (1)ketoconazole will increase the level or effect of vandetanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vardenafil

  Monitor Closely (1)ketoconazole will increase the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministered with ketoconazole 400 mg/day, limit vardenafil dose to 2.5 mg/24 hr. If coadministered with ketoconazole 200 mg/day, limit vardenafil dose to 5 mg/24 hr.

• vemurafenib

  Monitor Closely (1)ketoconazole increases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole increases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• venetoclax

  Contraindicated (1)ketoconazole 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%.

• venlafaxine

  Monitor Closely (2)ketoconazole and venlafaxine both increase QTc interval. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of venlafaxine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• verapamil

  Monitor Closely (1)ketoconazole will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)verapamil will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vilanterol/fluticasone furoate inhaled

  Monitor Closely (1)ketoconazole 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

• vilazodone

  Serious - Use Alternative (1)ketoconazole 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 vilazodone daily dose to 20 mg.

• vinblastine

  Monitor Closely (2)ketoconazole will increase the level or effect of vinblastine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vincristine

  Monitor Closely (2)ketoconazole will increase the level or effect of vincristine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vincristine liposomal

  Monitor Closely (2)ketoconazole will increase the level or effect of vincristine liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vinorelbine

  Monitor Closely (1)ketoconazole will increase the level or effect of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• voclosporin

  Contraindicated (1)ketoconazole will increase the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.Monitor Closely (1)voclosporin, ketoconazole. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

• vonoprazan

  Monitor Closely (1)vonoprazan will decrease the level or effect of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Separate administration by at least 1 hr before or 2 hr after ketoconazole.

• vorapaxar

  Serious - Use Alternative (1)ketoconazole increases levels of vorapaxar by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• voriconazole

  Monitor Closely (1)ketoconazole and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (2)ketoconazole will increase the level or effect of voriconazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  voriconazole will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• warfarin

  Monitor Closely (1)ketoconazole will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• zafirlukast

  Minor (1)zafirlukast will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zaleplon

  Monitor Closely (1)ketoconazole will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• zanubrutinib

  Monitor Closely (1)ketoconazole will increase the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce zanubrutinib (a CYP3A4 substrate) to 80 mg PO BID when coadministered with a moderate CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous zanubrutinib dose.

• zidovudine

  Monitor Closely (1)ketoconazole increases levels of zidovudine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ziprasidone

  Monitor Closely (1)ketoconazole will increase the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.

• zolpidem

  Monitor Closely (1)ketoconazole will increase the level or effect of zolpidem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• zonisamide

  Monitor Closely (1)ketoconazole will increase the level or effect of zonisamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.