Drug Interaction Report

MONITOR: Concomitant use of digitalis glycosides and beta-blockers may increase the risk of bradycardia. These agents slow atrioventricular conduction and decrease heart rate, hence they may have additive cardiac effects during coadministration. Some beta-blockers such as carvedilol, esmolol, and talinolol have also been reported to increase the systemic bioavailability of digoxin. The mechanism may involve enhanced absorption as well as reduced renal excretion of digoxin due to inhibition of intestinal and renal P-glycoprotein efflux transporter.

MANAGEMENT: Caution is advised during coadministration of digitalis glycosides and beta-blockers. Serum digitalis levels, heart rate, and blood pressure should be monitored closely, particularly during the first few weeks of concomitant therapy. Patients should be advised to notify their physician if they experience anorexia, nausea, visual changes, irregular heartbeat, slow pulse, dizziness, or syncope. Beta-blockers should not be used in patients with overt or decompensated congestive heart failure, as sympathetic stimulation may be a vital component in maintaining hemodynamic function in these patients and its inhibition by beta blockade may worsen the heart failure.

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.