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Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever rucaparib is added to or withdrawn from therapy with these drugs.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 enhance the oral bioavailability of bexarotene. In one clinical study, bexarotene peak plasma concentration (Cmax) and systemic exposure (AUC) resulting from a 75 to 300 mg dose were 35% and 48% higher, respectively, when administered after a fat-containing meal relative to a glucose solution. In all clinical trials, patients were instructed to take bexarotene with or immediately following a meal.

Coadministration with inhibitors of CYP450 3A4 such as grapefruit juice may theoretically increase the plasma concentrations of bexarotene. In vitro studies suggest that bexarotene is metabolized by CYP450 3A4. However, concomitant administration with multiple doses of ketoconazole, a potent CYP450 3A4 inhibitor, did not alter bexarotene plasma concentrations, which would imply that bexarotene elimination is not substantially dependent on CYP450 3A4 metabolism in vivo.

MANAGEMENT: Because safety and efficacy data are based upon administration with food, bexarotene should be administered once daily with a meal. Patients may want to avoid consuming large amounts of grapefruit or grapefruit juice.