Drug Interactions between dutasteride / tamsulosin and rucaparib

MONITOR: Coadministration with rucaparib may increase the plasma concentrations and the risk of adverse effects of drugs that are substrates of CYP450 3A4. The proposed mechanism is decreased clearance due to rucaparib-mediated inhibition of CYP450 3A4. In a clinical study, rucaparib increased midazolam Cmax and AUC by 1.13- and 1.38-fold, respectively.

MANAGEMENT: Caution is advised if rucaparib is used concomitantly with drugs that are substrates of CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever rucaparib is added to or withdrawn from therapy with these drugs. Patients should be monitored for the development of adverse effects.

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.