Drug Interaction Report

MONITOR: Based on in vitro data, coadministration of voriconazole with a protease inhibitor may result in increased plasma concentrations of one or both drugs. The proposed mechanism is competitive inhibition of the CYP450 3A4 isoenzyme, of which voriconazole and protease inhibitors are known substrates as well as inhibitors. However, coadministration of indinavir (800 mg three times a day for 10 days) reportedly had no significant effect on the steady-state peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of voriconazole (200 mg every 12 hours for 17 days) in healthy subjects. Voriconazole also did not significantly affect indinavir Cmax and AUC during coadministration for 7 days in healthy volunteers.

MANAGEMENT: Caution is advised if voriconazole must be used concomitantly with protease inhibitors. Patients should be frequently monitored for drug toxicity during coadministration of these drugs, and the dosage(s) adjusted accordingly.

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.

ADJUST DOSING INTERVAL: Food may reduce the systemic bioavailability of amprenavir from fosamprenavir oral suspension. The mechanism of interaction has not been described. According to the product labeling, administration of fosamprenavir oral suspension (1400 mg single dose) with a high-fat meal (967 kcal, 67 g fat, 33 g protein, 58 g carbohydrate) reduced amprenavir peak plasma concentration (Cmax) by 46% and systemic exposure (AUC) by 28% compared to administration in a fasted state. The time to reach peak plasma level (Tmax) was delayed by 0.72 hours. In contrast, the same high-fat meal did not affect the pharmacokinetics of amprenavir from fosamprenavir tablets.

MANAGEMENT: Fosamprenavir suspension should be administered on an empty stomach in adults, but with food in pediatric patients to aid palatability and compliance. If emesis occurs within 30 minutes after dosing the suspension, the dose should be repeated. Fosamprenavir tablets may be taken with or without food.