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Can Use of Oral Erythromycin Lead to Sudden Cardiac Death?

Risks from erythromycin use and from concomitant CYP3A inhibitor use were evident in an analysis of a small number of sudden cardiac deaths.

Case reports have suggested a link between erythromycin and torsades de pointes, and erythromycin has been shown to prolong the QT interval. Concomitant use of medications that inhibit the cytochrome P₄₅₀ isoenzyme CYP3A, which metabolizes erythromycin, might increase the risk for arrhythmia. To assess whether oral erythromycin is associated with sudden cardiac death (SCD), researchers analyzed more than 1.2 million person-years of data from 1988 through 1993 in a Tennessee Medicaid cohort (mean age, 45; 70% women).

About 1500 SCDs were confirmed by reviewing medical records. The risk for SCD was twice as high among current users of erythromycin than among people who had not used erythromycin, any of a finite list of CYP3A inhibitors, or amoxicillin (an antibiotic that does not prolong the QT interval). Statistically elevated risk for SCD was not evident among current users of amoxicillin or former users of erythromycin. However, it's important to note the absolute number of SCDs among current erythromycin users (10 events in 5305 person-years) and among current amoxicillin users (8 events in 6846 person-years) -- a very small difference.

People who used erythromycin and CYP3A inhibitors concomitantly had more than five times the risk for SCD than those who used neither antibiotics nor CYP3A inhibitors. Again, however, the absolute risk increase was very small, as only three SCDs (in 194 person-years) occurred in the concomitant-use subgroup.

Comment: The authors' conclusion that patients should avoid concurrent use of erythromycin and CYP3A inhibitors (e.g., diltiazem, verapamil) seems prudent. Still, the finding is based on small absolute differences in the number of sudden cardiac deaths. Also, medical records were unavailable for many of the deaths in the database, undercutting the laudable decision to count only those SCDs that could be confirmed.

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology October 22, 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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