Drug Interactions between boceprevir and dutasteride / tamsulosin

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.

MONITOR: Based on in vitro data, coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of dutasteride, which is metabolized by the isoenzyme. No clinical drug interaction studies have been conducted. However, a population pharmacokinetic analysis found decreased clearance of dutasteride when it is coadministered with the moderate CYP450 3A4 inhibitors, verapamil and diltiazem (37% and 44%, respectively). In contrast, no decrease in dutasteride clearance was seen during coadministration with amlodipine, a calcium channel blocker that is not a CYP450 3A4 inhibitor.

MANAGEMENT: The possibility of prolonged and/or increased pharmacologic effects of dutasteride should be considered during concomitant therapy with CYP450 3A4 inhibitors, particularly potent ones like itraconazole, ketoconazole, posaconazole, voriconazole, conivaptan, nefazodone, cobicistat, delavirdine, protease inhibitors, and ketolide and certain macrolide antibiotics.