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as well as clinical and laboratory monitoring may be appropriate for some drugs whenever elagolix is added to or withdrawn from therapy.

Administration of digoxin with a high-fiber meal has been shown to decrease its bioavailability by almost 20%. Fiber can sequester up to 45% of the drug when given orally. Patients should be advised to maintain a regular diet without significant fluctuation in fiber intake while digoxin is being titrated.

Grapefruit juice may modestly increase the plasma concentrations of digoxin. The mechanism is increased absorption of digoxin due to mild inhibition of intestinal P-glycoprotein by certain compounds present in grapefruits. In 12 healthy volunteers, administration of grapefruit juice with and 30 minutes before, as well as 3.5, 7.5, and 11.5 hours after a single digoxin dose (0.5 mg) increased the mean area under the plasma concentration-time curve (AUC) of digoxin by just 9% compared to administration with water. Moreover, P-glycoprotein genetic polymorphism does not appear to influence the magnitude of the effects of grapefruit juice on digoxin. Thus, the interaction is unlikely to be of clinical significance.