Drug Interaction Report

MONITOR: In one small study digoxin serum concentrations decreased by 40% in two of ten patients also receiving aminosalicylic acid at a dosage of 2 grams four times a day. Digoxin levels were not changed in the remaining eight patients.

MANAGEMENT: The clinician may want to monitor serum digoxin levels more closely and observe the patient for subtherapeutic effects if these agents are used concomitantly. Patients should be advised to notify their physician if they experience a worsening of their symptoms.

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.