Midoneck SR, Etingin OR
Clarithromycin-related toxic effects of digoxin

N Engl J Med (Nov) 333:1505, 1995

Midoneck and Etingin report an 81 year old woman who developed nausea, confusion, and a prolonged QTc interval with a digoxin serum level of 3.7 ng/ml four days after starting therapy for bronchitis with clarithromycin. Both drugs were discontinued. Three days later, her symptoms had improved and her digoxin serum level was 1.0 ng/ml. Four weeks after resuming digoxin therapy without clarithromycin, the digoxin serum level was 0.8 ng/ml. No change in renal function was observed. The authors postulate that an interaction between clarithromycin and digoxin resulted in increased digoxin absorption and digitalis toxicity.

Comments:
Dr. George R. Aronoff, M.D. (Louisville, KY) (Send questions and suggestions to: graron01@ulkyvm.louisville.edu):

Orally administered digoxin may be converted into inactive reduction products, such as dihydrodigoxin, by colonic bacteria. In some patients, the bioavailability of digoxin is decreased by 40 percent through bacterial metabolism before the drug is absorbed. Inhibition of these microorganisms could result is substantially increased active digoxin absorption.

Inactivation of digoxin metabolizing gut bacteria has previously been reported for erythromycin (1) and a similar case of suggested clarithromycin induced digoxin toxicity has been reported (2). Consequently, intermittent antibiotic therapy might lead to digoxin toxicity, in patients with previously stable digoxin serum levels. Clinicians should be aware of this potentially important drug interaction.

References:
(1) Lindenbaum J, Rund DG, Butler VP, et al. Inactivation of digoxin by the gut flora: reversal by antibiotic therapy. N Engl J Med 1981;305:789-94.
(2) Taylor JW, Gammenthaler SA, Rape JM. Clarithromycin induced digoxintoxicity. Presented at the American Society of Healthcare Pharmacists Midyear Clinical Meeting, Miami, December 1994, abstract.
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