Drug Interaction Report

Coadministration with lone inducers of CYP450 3A4 is unlikely to decrease the plasma concentrations of relugolix to a clinically significant extent. In vitro, relugolix is metabolized primarily by CYP450 3A and, to a lesser extent, by CYP450 2C8. Relugolix is also a substrate for intestinal P-gp. When relugolix was coadministered with rifampin, a combined P-gp and potent CYP450 3A inducer, relugolix peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 23% and 55%, respectively. By contrast, no clinically significant differences in the pharmacokinetics of relugolix were observed when coadministered with enzalutamide, a strong CYP450 3A inducer that is not known to induce P-gp.

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.