Drug Interaction Report

Theoretically, coadministration with inducers of CYP450 3A4 and/or P-glycoprotein (P-gp) may decrease the plasma concentrations of rivaroxaban, which is a substrate of the isoenzyme as well as the efflux transporter. In a pharmacokinetic study, administration of a single 20 mg dose of rivaroxaban with the potent CYP450 3A4 and P-gp inducer rifampin (titrated up to 600 mg once daily) resulted in approximately 22% and 50% decreases in mean rivaroxaban peak plasma concentration (Cmax) and system exposure (AUC), respectively, with parallel decreases in its pharmacodynamic effects. The effects of less potent inducers of either CYP450 3A4 or P-gp have not been studied.

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.