Correspondence

Clarithromycin-Related Toxic Effects of Digoxin

N Engl J Med 1995; 333:1505November 30, 1995

Article

To the Editor:

Digitalis glycosides and macrolide antibiotics are both commonly prescribed medications. Erythromycin prolongs the clearance of digoxin by altering the flora in the distal portion of the intestine that metabolizes digoxin to various inactive compounds that can be found in the stool and urine. When erythromycin is ingested by patients receiving oral or intravenous digoxin, the formation of these metabolites decreases and serum digoxin concentrations increase substantially.1 Clarithromycin may have a similar effect on the metabolism of digoxin. We report the occurrence of elevated serum digoxin concentrations and toxic effects of digoxin during clarithromycin therapy in a patient receiving long-term digoxin therapy.

The patient was an 81-year-old woman with hypertension and normal renal function. For over five years, she had been taking 0.25 mg of digoxin per day orally to treat premature atrial contractions and 25 mg of atenolol per day orally to treat hypertension. Four days after she began taking clarithromycin (500 mg twice daily) for bronchitis, nausea and confusion developed, and she was hospitalized. Her serum digoxin concentration was 3.7 ng per milliliter; it had been 1.0 ng per milliliter eight weeks previously. Her serum creatinine concentration at the time of admission was 0.7 mg per deciliter (62 μmol per liter). An electrocardiogram revealed a prolonged QTc interval (440 msec). Digoxin and clarithromycin were discontinued. The patient's symptoms improved within two days. Three days after admission, her serum digoxin concentration was 1.0 ng per milliliter, and her electrocardiogram was normal. Digoxin therapy was resumed at a dose of 0.125 mg per day after her discharge from the hospital. Four weeks later, her serum digoxin concentration was 0.8 ng per milliliter.

A similar patient was described at a recent meeting of the American Society of Healthcare Pharmacists.2 In view of the increasing use of clarithromycin, clinicians should be aware of the possibility of digoxin-related intoxication in patients taking both drugs at the same time.

Shari R. Midoneck, M.D.
Orli R. Etingin, M.D.
New York Hospital–Cornell Medical Center, New York, NY 10021

2 References

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   Lindenbaum J, Rund DG, Butler VP Jr, Tse-Eng D, Saha JR. Inactivation of digoxin by the gut flora: reversal by antibiotic therapy. N Engl J Med 1981;305:789-794
   Full Text | Web of Science | Medline

2. 2

   Taylor JW, Gammenthaler SA, Rape JM. Clarithromycin (Biaxin) induced digoxin toxicity. Presented at the American Society of Healthcare Pharmacists Midyear Clinical Meeting, Miami, December 1994. abstract.
   

Citing Articles (6)

Citing Articles

1. 1

   Agnes L. F. Chan, Meng-Ting Wang, Chen-Yi Su, Fu-Hsiung Tsai. (2009) Risk of digoxin intoxication caused by clarithromycin–digoxin interactions in heart failure patients: a population-based study. European Journal of Clinical Pharmacology 65:12, 1237-1243
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2. 2

   Ichiro Ieiri, Hiroshi Takane, Kenji Otsubo. (2004) The MDR1 (ABCB1) Gene Polymorphism and its Clinical Implications. Clinical Pharmacokinetics 43:9, 553-576
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3. 3

   Scott A. McConnell, Guy W. Amsden. (1999) Review and Comparison of Advanced-Generation Macrolides Clarithromycin and Dirithromycin. Pharmacotherapy 19:4, 404-415
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4. 4

   Hiroko Wakasugi, Ikuko Yano, Tatsuya Ito, Tohru Hashida, Takahiro Futami, Ryuji Nohara, Shigetake Sasayama, Ken-ichi Inui. (1998) Effect of clarithromycin on renal excretion of digoxin: Interaction with P-glycoprotein*. Clinical Pharmacology & Therapeutics 64:1, 123-128
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5. 5

   Dieter Paar, Birgit Terjung, Tilman Sauerbrach. (1997) Life-threatening interaction between clarithromycin and disopyramide. The Lancet 349:9048, 326-327
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6. 6

   &NA;. (1995) Digoxin interaction. Reactions Weekly &NA;:580, 5
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