Drug Interaction Report

Coadministration with inhibitors of the isoenzyme CYP450 3A4 may increase the plasma concentrations and effects of maribavir, a CYP450 3A4 substrate. When a single 400 mg dose of maribavir was administered with a single 400 mg dose of ketoconazole, a potent CYP450 3A4 and P-glycoprotein (P-gp) inhibitor, mean maribavir peak plasma concentration (Cmax) and total systemic exposure (AUC) increased by 10% and 53%, respectively, in 19 study subjects. These changes are not considered clinically significant. No dosage adjustments are necessary when maribavir is prescribed with CYP450 3A4 inhibitors, but it may be advisable to monitor patients for maribavir-related adverse effects such as taste disturbances, nausea, diarrhea, vomiting, and fatigue.

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.