Sept. 8, 2004 A popular antibiotic may dramatically raise the risk of sudden cardiac death when used in combination with a group of commonly used drugs, according to new research.
In a large study, researchers found the risk of sudden death caused by an abnormally rapid heart rhythm was up to five times higher in people taking erythromycin in combination with a group of drugs that can raise the level of erythromycin in the blood.
In the study, the risk of sudden cardiac death was also twice as high among people using erythromycin alone.
Erythromycin is an antibiotic that has been widely used to treat a variety of infections in the last 30 years and is considered relatively safe with a low risk of side effects.
Although the study suggests that the risk of sudden cardiac death is higher among people using the drug, the overall risk of sudden cardiac death among healthy people is still very low. However, researchers say the results show that erythromycin should not be used together with medications that increase the blood level of the antibiotic.
Medications that cause erythromycin to build up in the bloodstream include:

The antifungal medications Nizoral and Diflucan
Some drugs that treat high blood pressure or heart disease, such as Cardizem, Cartia, Dilacor, Diltia, Tiazac, Teczem, Calan, CoveraHS, Isoptin, Verelan, and Tarka
The antiHIV drug Crixivan
The antibiotic drug Tao
The antidepressant Serzone

These drugs are known as CYP3A inhibitors.
Drug Interactions Raise Sudden Death Risks
For the study, published in the Sept. 9 issue of The New England Journal of Medicine, researchers reviewed the medical records of Tennessee Medicaid recipients who died from 1988 to 1993. Researchers looked for any association between the use of erythromycin and sudden cardiac death and whether this risk was affected by use of drugs known to increase the blood level of the antibiotic.
Nearly 1,500 cases of sudden cardiac death occurred during the study period, and researchers found that the rate of sudden cardiac death was twice as high among people using erythromycin.
There was no increase in risk among those who had previously used the antibiotic or among those using another antibiotic, amoxicillin, which is used in many of the same situations as erythromycin.
In addition, the study showed that the rate of sudden cardiac death was five times as high among people who were using erythromycin and one of the CYP3A inhibitors. But there was no increase in risk among those using CYP3A inhibitors and amoxicillin.
Benefits vs. Risks Must Be Weighed
Researchers say erythromycin, alone and especially in combination with this group of drugs, may increase the risk of sudden cardiac death by slightly altering the normal heart rhythm, specifically by prolonging a portion called the QT interval. Prolonging the QT interval is known to be associated with an increase in potentially deadly heart rhythms.
In a related article published in the same journal, Barbara Liu, MD, and David Juurlink, MD, PhD, of the University of Toronto, say this study shows weighing the benefits and risks of potential drug interactions of potentially lifesaving drugs is a complex process.
For people without other risk factors for sudden cardiac death, they say the risk of using a single drug that prolongs the QT interval is probably extremely low, “as evidenced by the millions of courses of erythromycin that have been taken safely during the past 30 years.
“However, for patients with other preexisting drugrelated or nondrugrelated risk factors, QTintervalprolonging drugs should be used very cautiously and only after the risks and benefits have been weighed on a casebycase basis,” they write.

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