Drug Interaction Report

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Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever rucaparib is added to or withdrawn from therapy with these drugs.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.

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.