March 19, 2014
Study Says FDA Was Right: Some Antibiotics Riskier
for Arrhythmia

Columbia, SC—When it comes to avoiding potentially fatal heart rhythms, amoxicillin appears to be a safer antibiotic choice than either azithromycin or levofloxacin, according to a new study.

The study, published recently in the Annals of Family Medicine, found that, compared with amoxicillin, azithromycin resulted in a statistically significant increase in mortality and arrhythmia risks on Days 1 to 5, but not 6 to 10. Levofloxacin, usually dispensed for a minimum of 10 days, resulted in an increased risk throughout the 10-day period.

University of South Carolina researchers embarked on the study following the 2013 FDA warning on azithromycin use and the risk of potential fatal heart rhythms.

In 2011, outpatient prescriptions for azithromycin were written for more than 40 million patients in the U.S., according to the article.

Postmarketing surveillance reports, as well as published studies, found cardiovascular risks, and the FDA approved revisions to azithromycin product labels regarding risks of QT prolongation. In March 2013, the FDA announced the warning was supported by results of a clinical QT interval study conducted by the manufacturer of azithromycin, which found that the drug prolonged the QT interval.

The investigators evaluated a large cohort of patients at the Department of Veterans Affairs between 1999 and 2012 to investigate whether cardiac arrhythmia and mortality risks are observed in older males receiving azithromycin, amoxicillin, and levofloxacin. The study analyzed more than 1.6 million unique antibiotic prescriptions, including 979,380 for amoxicillin, 201,798 for levofloxacin, and 594,792 for azithromycin for patients averaging 56.8 years old.

Overall, a higher risk of death was associated with azithromycin and levofloxacin therapies compared with amoxicillin.

Specifically, the researchers found a short course of azithromycin therapy was associated with statistically significant hazard ratios of 1.48 for mortality risks and 1.77 for serious arrhythmia risks within the first 5 days of treatment. That the risk of these events was not significantly increased for Days 6 to 10 likely was explained by the traditional 5-day prescription for azithromycin, the authors point out.

Levofloxacin also had statistically significant hazard ratios of 2.49 for mortality risk and 2.43 for serious arrhythmia risk when compared to amoxicillin, the report notes. The increased risk lasted the full 10 days for which the antibiotic is usually prescribed.

“Our results provide support for recent safety announcements from the manufacturer and the Food and Drug Administration (FDA),” the authors write.

Although the researchers said it could not be determined from the study which alternative antibiotics may be safer in every instance, they recommended, “Risks and benefits of antibacterial therapies should be considered when making prescription decisions,” the authors suggest. “As compared with amoxicillin, there was higher risk of death associated with azithromycin therapy administered to U.S. veterans. There are usually multiple antibiotic choices available for older patients, especially those with cardiac comorbidities; physicians may consider prescribing medications other than azithromycin and levofloxacin.”

U.S. Pharmacist Social Connect