Drug Interaction Report

Epoprostenol may decrease clearance of oral digoxin. The mechanism has not been determined. Theoretically, this interaction could lead to higher digoxin plasma concentrations and could potentiate toxicity. One pilot study noted a 15% decrease in clearance (which was statistically significant) on day 3 of administration. However, this change was not apparent by day 87. The change in digoxin clearance would not be expected to be clinically significant, except possibly in patients with higher baseline digoxin levels. Epoprostenol and digoxin have been used safely together during epoprostenol clinical trials.

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.