Drug Interaction Report

MONITOR: The use of some antineoplastic agents has been associated with decreased gastrointestinal absorption of digoxin. The suspected mechanism is alteration of the gastrointestinal mucosa. The risk of an interaction is expected to be less with digoxin solution in capsules because absorption occurs rapidly in the upper GI tract.

MANAGEMENT: Digoxin serum levels and effectiveness should be monitored closely following the initiation or discontinuation of antineoplastic agents, and the dosage adjusted as necessary.

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.