Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of the hepatitis C virus (HCV) NS3/4A protease inhibitors, boceprevir and telaprevir, which are metabolized by the isoenzyme. In 16 study subjects, administration of a single 750 mg dose of telaprevir during treatment with the potent CYP450 3A4 inducer rifampin (600 mg daily for 7 days) reduced the telaprevir peak plasma concentration (Cmax) and systemic exposure (AUC) by an average of 86% and 92%, respectively, compared to administration alone. No data are available for boceprevir; however, a similar interaction is expected.

MANAGEMENT: Caution is recommended if boceprevir or telaprevir is used in combination with a CYP450 3A4 inducer. Close clinical monitoring of the virologic response to the HCV NS3/4A protease inhibitor is recommended.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

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.