By Daniel J. DeNoon
WebMD Health News

Reviewed by Laura J. Martin, MD

May 16, 2012 -- Sudden heart death may be a new risk from the commonly prescribed antibiotic azithromycin -- better known as Zithromax or the Z-Pak.

The finding comes from a study of Medicaid patients who received some 348,000 Z-Pak prescriptions from 1992 to 2006.

Compared to patients who took no antibiotics, those taking the five-day course of azithromycin treatment had about a threefold higher risk of heart death. Compared to patients with infections treated with amoxicillin, another antibiotic, those taking azithromycin had twice the risk of heart death.

Even so, it's a small risk. For every million courses of azithromycin treatment there were an estimated 47 extra heart deaths. Among people at highest risk of heart disease, there were 245 extra heart deaths per million courses of azithromycin.

"It's a small risk. And if you look carefully, you'll see that all antibiotics have serious risks," study leader Wayne A. Ray, PhD, professor of preventive medicine at Vanderbilt University, tells WebMD. "For most patients, this is a relatively small risk."

Ray says the study probably will make doctors think hard about prescribing azithromycin for patients at high risk of heart death.

"When an equally effective alternative is available, it should be used for patients at high cardiac risk," Ray says.

Infectious disease specialist Jay Varkey, MD, director of the antibiotic management program at Emory University, says the study is well done but far from conclusive.

"In and of itself, this study does not warrant a dramatic amount of alarm," Varkey tells WebMD. "It calls for more studies to see whether the increased death rate was truly due to azithromycin or to the underlying disease being treated."

Ray and colleagues tried to do this by comparing patients on azithromycin to those on amoxicillin. Both drugs are often used to treat ear, nose, and throat infections.

But Varkey notes that azithromycin is more likely to be used in patients with pneumonia, which might mean that those taking the drug were already at higher risk of death.

While the findings certainly will make Varkey pause before prescribing a Z-Pak to a patient with heart disease, he says the biggest risk to patients is from taking unnecessary antibiotics in the first place.

"At least half of antibiotic prescriptions are unnecessary and inappropriate," he says. "The first question to all doctors is, 'Does this person really need an antibiotic?'"

The study appears in the May 17 issue of The New England Journal of Medicine.