Common antibiotic can pose risk

November 2004

Recent research about the increased risk of sudden death with erythromycin has raised concerns about how best to determine which patients should avoid this antibiotic.

We have known for some time that erythromycin can prolong cardiac repolarization and that it has been linked with reports of torsades de pointes. We also have known about the potential increased risk of ventricular arrhythmias and sudden death when the drug is coadministered with other drugs influencing CYP3A.

But this carefully designed study, published in The New England Journal of Medicine, should increase our level of concern. Michael Stein and colleagues found that the rate of sudden death from cardiac causes among patients using erythromycin was twice as high as the rate for patients who had not used any antibiotic. The adjusted rate of sudden death from cardiac causes was five times as high among patients who were using CYP3A inhibitors and erythromycin as among patients who had used neither the inhibitors nor any of the study antibiotics. Investigators found no increased risk of sudden death among patients who were using amoxicillin and CYP3A inhibitors. The CYP3A inhibitors used in the study included nitroimidazole antifungal agents, diltiazem, verapamil and troleandomycin (Tao, Pfizer).

Concurrent use contraindicated

There were some limitations to this study: No dose or duration information was given, and few cases with the commonly used calcium antagonists diltiazem and verapamil were included. However, their conclusion appears sound: Erythromycin should not be used concurrently with strong inhibitors of CYP3A.

I recommend that physicians considering erythromycin do the following:

• Order an electrocardiogram (ECG) on any patient that you want to start on erythromycin to exclude the rare patient with QT prolongation (either hereditary or drug-induced). If a patient is identified, do not prescribe erythromycin.
• Develop a list of drugs that are metabolized by or inhibit CYP3A. If the patient is taking one of these drugs, I would avoid prescribing erythromycin. Of particular concern in the research was the coadministration of diltiazem, verapamil or an antifungal agent. Cimetidine was listed as not being a concern but no data were offered to support that. I would also include cimetidine on the list.

Assuming that none of the above is present, it seems reasonable to start erythromycin. After you dose titrate, I recommend that you repeat the ECG looking for QT prolongation. If the QT is not prolonged, it seems reasonable to continue for the long term. I would caution the patient — and the referring physician — about adding one of the other drugs on the CYP3A list.

No practice guidelines are available for this yet, so it is wise to practice defensive medicine given this latest research. The cost and inconvenience of two ECGs is minimal. Developing the drug list is simply good medical practice.

For more information:

• Ray WA, Murray KT, Meredith S, et al. Oral erythromycin and the risk of sudden death from cardiac causes. N Engl J Med. 2004;351(11):1089-1096.
• Erythromycin may increase sudden cardiac death risk. Infect Dis News. 2004;17(10):12.

• Carl Pepine, MD, is Chief Medical Editor of Today in Cardiology, a sister publication of Infectious Disease News, and is professor of medicine and chief of the division of cardiovascular medicine at the University of Florida, Gainesville.