Interactions

Drug-Drug

• Ketoconazole inhibits the hepatic P450 3A4 enzyme system, which results in ↓ metabolism and possibly ↑ effects and/or toxicity from cyclosporine , tacrolimus , corticosteroids (dosage reduction may be necessary), calcium channel blockers , sulfonylurea , oral hypoglycemic agents , quinidine , buspirone , clarithromycin , troleandomycin , erythromycin , cyclophosphamide , phenytoin , warfarin (↑ risk of bleeding), tamoxifen , tricyclic antidepressants , carbamazepine , nisoldipine , zolpidem , vinca alkaloids , ifosfamide , some benzodiazepines (effect may persist for several days; use of triazolam is contraindicated), alfentanil , fentanyl , sufentanil , donepezil , atorvastatin , lovastatin , simvastatin , amprenavir , indinavir (dosage ↓ of indinavir recommended), nelfinavir , ritonavir , saquinavir , quinidine , sildenafil and vardenafil (dosage adjustments may be necessary)

• May alter the effectiveness of hormonal contraceptives (alternative method of contraception recommended)

• Drugs that ↑ gastric pH, including antacids , histamine H2 antagonists , didanosine (chewable tablets, because of buffer), and gastric acid–pump inhibitors ↓ absorption (wait 2 hr before administration of ketoconazole)

• Sucralfate and isoniazid also ↓ bioavailability

• ↑ hepatotoxicity with other hepatotoxic agents , including alcohol

• Disulfiram-like reaction may occur with alcohol

• Rifampin or isoniazid may ↓ levels and effectiveness

• May ↓ absorption and effectiveness of theophylline

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