Drug Interaction Report

MONITOR: Coadministration with H2-receptor antagonists or inhibitors of the proton pump (PPIs or potassium-competitive acid blockers [PCABs]) may decrease the oral bioavailability of amprenavir from its prodrug, fosamprenavir. In 30 study subjects, ranitidine (300 mg single oral dose) decreased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amprenavir from fosamprenavir (1400 mg single oral dose) by 51% and 30%, respectively, compared to administration of fosamprenavir alone. The mechanism of interaction has not been described. It is possible that fosamprenavir solubility decreases with increasing pH, thus inhibition of gastric acid secretion may interfere with dissolution of the drug. Subtherapeutic antiretroviral drug levels may lead to reduced viral susceptibility and development of resistance.

MANAGEMENT: Caution is advised if fosamprenavir is prescribed with H2-receptor antagonists or inhibitors of the proton pump. Antiretroviral response should be monitored closely during coadministration.

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.