Those who take the popular macrolide antibiotic azithromycin (Zithromax or Z-Pak) – used to treat a wide variety of bacterial infections by stopping the growth of bacteria – face a risk of cardiovascular death, according to the U.S. Food and Drug Administration.

The FDA warning came after The New England Journal of Medicine published the results of a study comparing the risks of heart-related deaths in patients in patients treated with azithromycin (Zithromax), amoxicillin, ciprofloxacin (Cipro), levofloxacin (Levaquin), and no antibacterial drug.

The study reported a small increase in cardiovascular deaths, and the risk of death from any cause, in patients who took a five-day course of Zithromax compared to the other medications.

According to Reuters, the FDA issued the warning on the heels of both the New England Journal of Medicine study as well as a review of a study by medical researchers and a company study assessing the drug’s potential for causing abnormal changes in the electrical activity of the heart.

Zithromax manufacturer Pfizer issued a statement saying “Zithromax has had a well-established benefit risk profile for more than 20 years and continues to be an effective treatment option for patients all over the globe suffering from many types of bacterial infections.”

In 2011, according to Reuters, citing IMS Health, U.S. sales of Zithromax exceeded $450 million.

The results of a 14-year Vanderbilt University study found that Zithromax substantially increases a patient’s chances for sudden deadly heart problems.

Patients who took the drug were found to more than double their risk of heart death. Zithromax is prescribed to treat such ailments as bacterial respiratory infections, skin infections, ear infections, and sexually transmitted diseases.

The Vanderbilt study analyzed health records and data on millions of prescriptions for several antibiotics given to some 540,000 Tennessee Medicaid patients – all of whom started out with comparable risks for heart trouble – between 1992 and 2006.

There were 29 heart-related deaths by patients taking Zithromax during five days of treatment, more than double that of patients on another antibiotic, amoxicillin, or those who took none.

“The results suggest there would be 47 extra heart-related deaths per 1 million courses of treatment with Zithromax, compared with amoxicillin,” according to a story by CBS news.

Zithromax is popular because it works more quickly than other antibiotics, but increasingly, consumers are filing complaints about Z-Pak side effects.

In March 2013, the FDA announced that azithromycin can cause abnormal changes in the electrical activity of the heart that may lead to a potentially fatal irregular heart rhythm. Patients with preexisting heart disease comprised the highest risk group.

The FDA required drug labels to be updated to strengthen the Warnings and Precautions section with information related to the risk of “a specific, rare heart rhythm abnormality” known as QT interval prolongation and torsades de pointes.