Drug Interactions between Lanoxin and Zee-Seltzer Antacid and Pain Reliever

MONITOR: Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase plasma digoxin concentrations and half-life. The exact mechanism is unknown, but may be related to reduced renal clearance of digoxin. Data have been conflicting. The interaction has been reported with indomethacin and ibuprofen, but data for other NSAIDs are not available.

MANAGEMENT: Patients who require concomitant therapy should be monitored for altered pharmacologic effects of digoxin and for increased plasma levels. The digoxin dosage may require adjustment. Patients should be advised to notify their physician if they experience nausea, anorexia, visual changes, slow pulse, or irregular heartbeats.

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MONITOR: Agents that cause urinary alkalinization can reduce serum salicylate concentrations in patients receiving anti-inflammatory dosages of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to increased urinary pH, resulting in increased renal salicylate clearance especially above urine pH of 7. This interaction is sometimes exploited in the treatment of salicylate toxicity.

MANAGEMENT: Patients treated chronically with urinary alkalinizers and large doses of salicylates (i.e. 3 g/day or more) should be monitored for potentially diminished or inadequate analgesic and anti-inflammatory effects, and the salicylate dosage adjusted if necessary.

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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.

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