Drug Interaction Report

MONITOR: Coadministration with voriconazole may increase the plasma concentrations of drugs that are substrates of CYP450 2C19, 2C9, and/or 3A4. The mechanism is decreased clearance due to inhibition of those isoenzymes by voriconazole. Increased plasma levels and/or pharmacologic effects of drugs such as cyclosporine, sirolimus, tacrolimus (3A4 substrates), and warfarin (2C9 substrate) have been reported during coadministration with voriconazole.

MANAGEMENT: Caution is advised if voriconazole must be used concomitantly with medications that undergo metabolism by CYP450 2C19, 2C9 and/or 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever voriconazole is added to or withdrawn from therapy. The manufacturer specifically recommends that a dosage reduction be considered for benzodiazepines, statins, long-acting opiates, and vinca alkaloids that are metabolized by the affected isoenzymes when used with voriconazole.

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.