Drug Interaction Report

Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of doravirine, which is primarily metabolized by the isoenzyme. In 10 study subjects, administration of a single 50 mg dose of doravirine with the potent CYP450 3A4 inhibitor ritonavir (100 mg twice daily) increased doravirine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (C24hr) by an average of 31%, 254% and 191%, respectively, compared to administration of doravirine alone. When a single 100 mg dose of doravirine was administered with ketoconazole 400 mg once daily in 10 study subjects, doravirine Cmax, AUC and C24hr increased by an average of 25%, 206% and 175%, respectively. These changes are not considered clinically significant.

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of boceprevir. When given at 800 mg three times daily with food, boceprevir exposure increased by up to 65% relative to administration in the fasting state. The bioavailability of boceprevir was similar regardless of meal type (e.g., high-fat versus low-fat) or whether taken 5 minutes prior to eating, during a meal, or immediately following completion of the meal. Therefore, boceprevir may be taken without regard to either meal type or timing of the meal.

MANAGEMENT: To ensure maximal oral absorption, boceprevir should be administered with a meal or light snack.