Drug Interaction Report

GENERALLY AVOID: Coadministration with inhibitors of the hepatic influx transporters organic anion transporting polypeptides (OATP) 1B1 and/or 1B3 may increase the plasma concentrations and adverse effects of atrasentan. In clinical studies, coadministration with the OATP1B1 and 1B3 inhibitor cyclosporine increased the mean systemic exposure (AUC) and peak plasma concentration (Cmax) of atrasentan (single dose, 10 mg) by 380% and 430%, respectively. The risk of adverse effects such as edema, hepatotoxicity and anemia may be increased with this combination.

MANAGEMENT: Concomitant use of atrasentan with OATP1B1 and/or 1B3 inhibitors should generally be avoided.

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.