Drug-Drug: Thiazide and loop diuretics, piperacillin , ticarcillin, amphotericin B, corticosteroids, and excessive use of laxatives may cause hypokalemia which may ↑ risk of toxicity. Amiodarone, some benzodiazepines, cyclosporine, diphenoxylate, indomethacin, itraconazole, propafenone,,quinidine, quinine, spironolactone and verapamil may ↑ levels and lead to toxicity (serum level monitoring/dose reduction may be required). Levels may be ↓ by some antineoplastics (bleomycin, carmustine, cyclophosphamide, cytarabine, doxorubicin, methotrexate, procarbazine, vincristine), activated charcoal, cholestyramine, colestipol, kaolin/pectin, metoclopramide, penicillamine, rifampin or sulfasalazine. In a small percentage (10%) of patients gut bacteria metabolize digoxin to inactive compounds; macrolide anti-infectives (erythromycin, azithromycin, clarithromycin), tetracyclines, by killing these bacteria, will cause ↑ levels and toxicity; dose may need to be ↓ for up to 9 weeks. Additive bradycardia may occur with beta blockers, diltiazem, verapamil, clonidine, and other antiarrhythmics (quinidine, disopyramide). Concurrent use of sympathomimetics may ↑ risk of arrthythmias. Thyroid hormones may ↓ therapeutic effects.
Drug-Natural: Licorice and stimulant natural products (aloe) may ↑ risk of potassium depletion. St. John's wort may ↓ levels and effect.
Drug-Food: Concurrent ingestion of a high-fiber meal may ↓ absorption. Administer digoxin 1 hour before or 2 hours after such a meal.