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Increased Risk for Sudden Death: Time to Toss Erythromycin from the Formulary

Combined use of erythromycin and CYP3A inhibitors (verapamil, diltiazem) increases the risk of sudden death fivefold.

Oral erythromycin prolongs cardiac repolarization. Because it is metabolized by cytochrome P-450 3A (CYP3A), drugs that inhibit CYP3A-mediated metabolism can raise erythromycin levels. To determine whether the interaction between erythromycin and CYP3A inhibitors (e.g., calcium-channel blockers) is associated with sudden death among patients taking both agents, these authors analyzed Tennessee Medicaid patient and pharmacy records from 1988 through 1993 (before introduction of azithromycin and widespread use of clarithromycin). Amoxicillin use also was reviewed to control for confounding by indications for antimicrobial use.

The records covered 1.25 million patient-years and 1476 cases of sudden death from cardiac causes. The rate of sudden death among patients currently using erythromycin alone (i.e., not with CYP3A inhibitors) was twice as high as that among patients who had not used either erythromycin or amoxicillin. Rates were not increased in former users of erythromycin or current users of amoxicillin. Among patients taking erythromycin concurrently with CYP3A inhibitors, the rate of sudden death was five times higher than that among patients who were not taking either agent. Rates were not increased in patients taking amoxicillin concurrently with CYP3A inhibitors or in those taking CYP3A inhibitors alone.

Comment: Erythromycin was never a great drug. Up to a third of patients taking it develop severe gastrointestinal symptoms. Now that it poses the danger of sudden death, it is time to retire this drug.

— J. Stephen Bohan, MD, MS, FACP, FACEP

Published in Journal Watch Emergency Medicine October 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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