Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 that also induce P-glycoprotein (P-gp) may significantly 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. Reduced efficacy of relugolix may occur. 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.

MANAGEMENT: Concomitant use of relugolix with combined P-gp and potent CYP450 3A inducers should generally be avoided. However, when relugolix is used as monotherapy for the treatment of prostate cancer and coadministration is required, the manufacturer recommends increasing the relugolix dosage to 240 mg once daily. Therapeutic response and tolerance should be monitored more frequently. Following discontinuation of the P-gp/CYP450 3A inducer, treatment with relugolix should be resumed at the normally recommended dosage of 120 mg once daily.