Drug Interaction Report

CONTRAINDICATED: Coadministration with boceprevir, a potent inhibitor of CYP450 3A4, may significantly increase the plasma concentrations of alpha 1-adrenergic blockers that are primarily metabolized by the isoenzyme. Severe hypotension and priapism may occur. Although the interaction has not been specifically studied with boceprevir, other potent CYP450 3A4 inhibitors like ketoconazole have been shown to increase the systemic exposure (AUC) to alfuzosin, silodosin and tamsulosin by approximately 3-fold. In one case report, a 44-year-old man with multiple comorbidities including HIV and HCV developed priapism nine days following the initiation of boceprevir. Among the multitude of drugs the patient was receiving, an interaction between boceprevir and doxazosin, tamsulosin, and/or quetiapine resulting in excessive alpha-1 adrenergic blockade was thought to be the probable cause. The patient required a surgically performed distal penile shunt to correct the problem.

MANAGEMENT: Concomitant use of boceprevir with alfuzosin, doxazosin, silodosin, or tamsulosin is considered contraindicated.

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of silodosin. The effect of a moderate-fat, moderate-calorie meal on silodosin pharmacokinetics was variable and decreased silodosin maximum plasma concentration (Cmax) by approximately 18% to 43% and systemic exposure (AUC) by 4% to 49% across three different studies. The maximum effect of food (i.e., coadministration with a high-fat, high-calorie meal) on the pharmacokinetics of silodosin was not evaluated. Safety and efficacy clinical trials for silodosin were always conducted in the presence of food intake.

MANAGEMENT: Patients should be instructed to take silodosin with a meal to reduce the risk of adverse events.

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.