Drug Interactions between Orilissa and vimseltinib

MONITOR: Coadministration with inhibitors of the OATP 1B1 hepatic uptake transporter, CYP450 3A4 metabolic isoenzyme, and/or P-glycoprotein (P-gp) efflux transporter may increase the plasma concentrations of elagolix. In 12 study subjects, coadministration of single doses of 150 mg elagolix and 600 mg rifampin, a known OATP 1B1 inhibitor, increased elagolix peak plasma concentration (Cmax) and systemic exposure (AUC) by 337% and 458%, respectively, compared to elagolix administered alone. When a single 150 mg dose of elagolix was administered to 11 study subjects during 400 mg once daily dosing of ketoconazole, a potent CYP450 3A4 inhibitor, elagolix Cmax and AUC increased by 77% and 120%, respectively. The effect of P-gp inhibitors on the pharmacokinetics of elagolix has not been studied, but some increases in elagolix exposure may occur, as it is a P-gp substrate. Increased exposure to elagolix may increase the risk of serious adverse effects such as bone loss, suicidal ideation and behavior, exacerbation of mood disorders, and hepatic transaminase elevations.

MANAGEMENT: Caution is advised when elagolix is used with OATP 1B1, CYP450 3A4, and/or P-gp inhibitors. Patients should be monitored for potentially altered effects of elagolix following the initiation or discontinuation of these inhibitors, and the elagolix dosage adjusted as necessary.