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Oral Erythromycin Increases the Risk for Sudden Cardiac Death

Oral erythromycin, long considered safe, increases risk for sudden cardiac death when taken in combination with CYP3A inhibitors.

Although erythromycin is generally considered to be a safe drug, some case reports have linked it to the serious ventricular arrhythmia torsades de pointes. In a recent government- and industry-supported study, researchers reviewed medical and pharmacy records for a cohort of Tennessee Medicaid recipients (totaling 1,249,943 person-years of care) to determine whether oral erythromycin increases the risk for sudden death and whether drug-drug interactions further potentiate such risk.

From 1988 through 1993, 1476 sudden cardiac deaths occurred in this cohort, for a rate of 1.2 deaths per 1000 person-years. The rate was approximately twice as high among individuals currently taking oral erythromycin as among those who had not taken it during the previous year (P=0.03). However, risk was not increased in patients who had taken oral erythromycin earlier during the previous year or in those currently taking amoxicillin, studied as a control agent. Sudden cardiac deaths increased to 15.5 per 1000 person-years among individuals who were concurrently taking oral erythromycin and any of six drugs (diltiazem; verapamil; troleandomycin; systemically administered fluconazole, ketoconazole, or itraconazole) that strongly inhibit cytochrome P-450 3A (CYP3A) and thus potentially increase erythromycin plasma concentrations (P=0.004). Rates were not increased in patients taking amoxicillin plus these CYP3A inhibitors or in those taking the CYP3A inhibitors alone.

Comment: Despite the large overall cohort, follow-up for individuals taking erythromycin plus CYP3A inhibitors was only 194 person-years. Of note, no cardiac deaths occurred among the few patients taking erythromycin plus an azole antifungal agent. Still, these findings suggest that such concurrent therapy should be used cautiously or avoided.

— Richard T. Ellison III, MD

Published in Journal Watch Infectious Diseases September 27, 2004

Citation(s):

Ray WA et al. Oral erythromycin and the risk of sudden death from cardiac causes. N Engl J Med 2004 Sep 9; 351:1089-96.

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