Drug Interaction Report

MONITOR: Coadministration of digoxin with etravirine may increase serum digoxin concentrations. The mechanism is unknown, but etravirine inhibition of p-glycoprotein-mediated transport may be involved.

MANAGEMENT: Caution and monitoring of serum digoxin levels are advised during concomitant use. The lowest dose of digoxin is recommended at initiation of digoxin therapy in patients receiving etravirine. Dose adjustments are not necessary upon initiation of etravirine therapy in patients who are stabilized on digoxin. Digoxin levels should be monitored and the dose titrated accordingly, as necessary. Patients should be advised to notify their physician if they experience potential signs and symptoms of digoxin toxicity such as nausea, anorexia, visual disturbances, slow pulse, or irregular heartbeats.

ADJUST DOSING INTERVAL: Coadministration with food increases the oral bioavailability of etravirine. The mechanism is unknown. Compared to administration following a meal, the systemic exposure (AUC) to etravirine was decreased by about 50% when the drug was administered under fasting conditions. The types of meal studied (ranging from 345 kilocalories containing 17 grams fat to 1160 kilocalories containing 70 grams fat) did not appear to make a difference with respect to impact on etravirine bioavailability.

MANAGEMENT: Etravirine should always be administered following a meal.

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.