Drug Interaction Report

MONITOR: Coadministration with albuterol decreases digoxin's serum concentration. The mechanism of action may involve an albuterol-induced increased distribution of digoxin to skeletal muscle. In a pharmacokinetic study, ten healthy patients were administered digoxin 0.5 mg daily for 10 days and then they were administered a single 3 mg or 4 mg oral dose of albuterol. This study reported a 22% decrease in serum digoxin levels and a 14% decrease in serum potassium after the albuterol dose. In addition, the effects of hypokalemia caused by beta-2 agonists such as albuterol may lead to an increased risk of digitalis induced arrhythmias. The clinical significance for patients who are receiving albuterol inhalation and digoxin is unclear.

MANAGEMENT: Caution is advised if albuterol is used concomitantly with digoxin. Monitoring of serum digoxin and potassium concentrations may be required. Clinical monitoring for digoxin toxicity and/or hypokalemia, particularly in patients at risk of hypokalemia should also be considered. Dosage adjustments for either medication may also be required whenever digoxin and albuterol are used concurrently. Patients should be advised to seek immediate medical attention if they experience signs of arrhythmias, such as sudden dizziness, lightheadedness, fainting, shortness of breath, or irregular heartbeats.

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.