Voriconazole is metabolized by CYP2C19, CYP2C9, and CYP3A4. The affinity of voriconazole is highest for CYP2C19, followed by CYP2C9, and is appreciably lower for CYP3A4. Inhbitors or inducers of these 3 enzymes may increase or decrease voriconazole systemic exposure (plasma concentrations), respectively.
Voriconazole inhibits the metabolic activity of CYP2C19, CYP2C9, and CYP3A4. The inhibition potency of voriconazole for CYP3A4 was significantly less than that of 2 other azoles, ketoconazole and itraconazole. The major metabolite of voriconazole, the voriconazole N-oxide, inhibits the metabolic activity of CYP2C9 and CYP3A4 to a greater extent than that of CYP2C19. There is potential for voriconazole and its major metabolite to increase the systemic exposure (plasma concentration) of other drugs metabolized by these CYP450 enzymes.
Drugs that affect voriconazole include the following: barbiturates (long acting), cimetidine, fluconazole, hormonal contraceptives, nonnucleoside reverse transcriptase inhibitors (NNRIs), phenytoin, protease inhibitors, proton pump inhibitors, rifampin, rifabutin and St. John's wort.
Drugs affected by voriconazole include the following: aripiprazole, benzodiazepines, cabazitaxel, calcium channel blockers, cisapride, clopidogrel, coumarin anticoagulants, cyclosporine, docetaxel, dronedarone, ergot alkaloids, erlotinib, erythromycin, hormonal contraceptives, HMG-CoA reductase inhibitors, ixabepilone, maraviroc, mammalian target of rapamycin inhibitors (eg, everolimus, temsirolimus), nilotinib, NNRTIs, nonsteroidal anti-inflammatory drugs, opioid analgesics, phenytoin, prednisolone, protease inhibitors, pimozide, proton pump inhibitors, quinidine, rifabutin, romidepsin, sirolimus, sulfonylureas, tacrolimus, tyrosine kinase receptor inhibitors, vinca alkaloids, zolpidem.