Drug Interaction Report

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of pimavanserin, which is primarily metabolized by the isoenzyme. According to the product labeling, pimavanserin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.5- and 3-fold, respectively, when given with the potent CYP450 3A4 inhibitor ketoconazole. High plasma levels of pimavanserin may increase the risk of QT interval prolongation, which has been associated with ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: Pimavanserin dosage should be reduced to 10 mg once a day when used with potent CYP450 3A4 inhibitors.

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.