Drug Interaction Report

Concurrent administration of antacids may decrease the oral bioavailability of digoxin and digitoxin. The mechanism of interaction is unknown. In ten healthy volunteers, administration of a single 0.75 mg dose of digoxin with 60 mL of antacid containing either 4% aluminum hydroxide gel, 8% magnesium hydroxide gel, or 8% magnesium trisilicate resulted in significantly reduced urinary excretion of digoxin (expressed as the percentage of original dose recovered) compared to administration without antacid. Specifically, the cumulative six-day urinary digoxin excretion was 40.1% for control, 30.7% for aluminum hydroxide, 27.1% for magnesium hydroxide, and 29.1% for magnesium trisilicate. In an in vitro study involving absorption across a physiological membrane, cumulative absorption of digoxin 0.25 mg was reduced 11.4% by aluminum hydroxide gel, 15.3% by light magnesium carbonate, and 99.5% by magnesium trisilicate. In a case report, an approximately 50% reduction in digoxin systemic exposure (AUC) was observed when digoxin was administered with 30 mL of an aluminum-magnesium hydroxide antacid and mexiletine. The interaction was attributed to the antacid, as mexiletine is not known to interact with digoxin. Some data also support a potential interaction with digitoxin. However, other studies have found no evidence of a significant interaction between digoxin and various antacids. Based on existing evidence, no special precautions appear necessary, although patients may consider separating the times of administration by 1 to 2 hours if an interaction is suspected.

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.