Drug Interaction Report

MONITOR: Limited clinical data suggest that hydantoins may reduce digoxin serum levels. The mechanism of this interaction is unknown. Although phenytoin has been used in the treatment of digitalis-induced arrhythmias, it has been associated with cardiac arrest in patients with marked heart block.

MANAGEMENT: If these drugs are used concomitantly, close monitoring for clinical and laboratory evidence of altered digitalis effect is recommended. Occasionally, increases in the digoxin dosage may be necessary. The clinician should be aware that the risk of digoxin toxicity may be increased when a hydantoin is discontinued and should consider monitoring the patient more closely for those effects. Phenytoin should be avoided in patients with marked digoxin-induced heart block or bradycardia.

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.