Drug Interaction Report

MONITOR: Coadministration with dual inducers of CYP450 3A4 and P-glycoprotein (P-gp) may decrease the plasma concentrations of relugolix. 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. The interaction has not been studied with other, less potent dual inducers of CYP450 3A4 and P-gp.

MANAGEMENT: The potential for diminished pharmacologic effects of relugolix should be considered during coadministration with dual CYP450 3A4 and P-gp inducers. Alternative treatments may be required if an interaction is suspected.