Drug Interaction Report

GENERALLY AVOID: Some hormonal contraceptives may decrease the plasma concentrations of amprenavir from fosamprenavir when it is administered in the absence of low-dose ritonavir as a pharmacokinetic booster. In contrast, fosamprenavir in combination with ritonavir may reduce the plasma levels of certain contraceptive hormones, and there is also an increased risk of transaminase elevations when these agents are used together. The mechanism of interaction has not been described. In 10 study subjects coadministered amprenavir (1200 mg twice a day for 28 days) and ethinyl estradiol-norethindrone (0.035 mg-1 mg for 1 cycle), amprenavir systemic exposure (AUC) and trough plasma concentration (Cmin) were reduced by 22% and 20%, respectively, compared to administration of amprenavir alone. Conversely, the Cmin of ethinyl estradiol was increased by 32%, while the Cmin and AUC of norethindrone were increased by 45% and 18%, respectively. When the same dose of contraceptive was coadministered with fosamprenavir/ritonavir (700 mg/100 mg twice a day) for three weeks in 25 study subjects, Cmax and AUC of ethinyl estradiol decreased by 28% and 37%, respectively. In addition, norethindrone Cmax, AUC and Cmin decreased by 38%, 34% and 26%, respectively. Amprenavir pharmacokinetics were not affected by the oral contraceptive. No data are available on the use of fosamprenavir/ritonavir with other hormonal therapies such as hormone replacement in postmenopausal women.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, alternative (i.e., nonhormonal) methods of birth control should be considered in patients treated with fosamprenavir.

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.