Drug Interaction Report

MONITOR: Coadministration with elagolix may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) transporter. The proposed mechanism is decreased clearance in the intestine, kidney, and/or liver due to inhibition of P-gp-mediated efflux by elagolix. When a single 0.5 mg dose of the probe P-gp substrate digoxin was coadministered with elagolix (200 mg twice daily for 10 days) in 11 study subjects, digoxin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 71% and 26%, respectively, compared digoxin administered alone.

MANAGEMENT: Caution is advised when elagolix is used concurrently with drugs that are P-gp substrates, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever elagolix is added to or withdrawn from therapy.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.