Drug Interaction Report

MONITOR: Coadministration with the hepatitis C virus (HCV) NS3/4A protease inhibitors, boceprevir and telaprevir, may decrease the plasma concentrations and efficacy of estrogens used for hormonal replacement therapy. The mechanism involves induction of CYP450 3A4, the isoenzyme primarily responsible for the metabolic clearance of sex hormones. When an oral contraceptive containing drospirenone-ethinyl estradiol (3 mg-0.02 mg daily for 14 days) was given in combination with boceprevir (800 mg three times daily for 7 days), ethinyl estradiol systemic exposure (AUC) decreased by approximately 25%, with no change in the peak plasma concentration (Cmax). In a study of 24 subjects who were administered an oral contraceptive containing ethinyl estradiol-norethindrone (0.035 mg-0.5 mg daily) concomitantly with telaprevir (750 mg every 8 hours) for 21 days, the Cmax and AUC of ethinyl estradiol decreased by 26% and 28%, respectively. In addition, there was a 33% reduction in the trough plasma concentration (Cmin) of ethinyl estradiol.

MANAGEMENT: Dosage adjustments as well as increased clinical and laboratory monitoring for estrogen deficiency should be considered whenever boceprevir or telaprevir is used concomitantly with estrogens used for hormonal replacement therapy.

MONITOR: Coadministration with boceprevir may increase the plasma concentrations of drugs that are metabolized by CYP450 3A4. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by boceprevir.

MANAGEMENT: Caution is advised if boceprevir must be used concomitantly with medications that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever boceprevir is added to or withdrawn from therapy.

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.