Clarithromycin-induced digoxin toxicity: a case report and a review of the literature

A 70-year-old woman with a history of atrial fibrillation, on digoxin, presented with nausea, vomiting, and dizziness two days after initiation of clarithromycin therapy. Laboratory results revealed a serum digoxin level of 3.9 ng/ml (normal range 0.5-2.0) and creatinine of 1.1 mg/dl. The patient was admitted to the hospital and digoxin and clarithromycin were discontinued. The patient's symptoms were resolved within 24 hours and her serum digoxin level was 1.9 on the second hospital day. A review of recent literature suggests that clarithromycin may induce digoxin toxicity by three different mechanisms, including reduction of renal excretion of digoxin, alteration of intestinal flora, and inhibition of cytochrome P-450 in the liver. Digoxin toxicity was reported three to 17 days after the initiation of clarithromycin (8.1 +/- 4.8 days, n = 9). The wide variation in the time required for the appearance of toxicity may imply the different mechanisms involved in each case.