Drug Interaction Report

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.

ADJUST DOSING INTERVAL: Food may delay the gastrointestinal absorption of tamsulosin. The time to maximum plasma concentration (Tmax) is reached by 4 to 5 hours under fasted conditions and by 6 to 7 hours when tamsulosin is administered with food. The delay in Tmax has the desirable effect of smoothing the tamsulosin plasma concentration profile, thereby reducing fluctuation of the plasma peak and trough concentrations with multiple dosing. Food may also affect the extent of absorption of tamsulosin. It has been reported that taking tamsulosin under fasted conditions results in a 30% increase in bioavailability (AUC) and 40% to 70% increase in peak plasma concentration (Cmax) compared to fed conditions. The effects of food on the pharmacokinetics of tamsulosin are consistent regardless of whether tamsulosin is taken with a light meal or a high-fat meal.

MANAGEMENT: To ensure uniformity of absorption, tamsulosin should be administered approximately one-half hour following the same meal each day.