Study: Zithromax associated with cardiovascular deaths; FDA reviewing

May 18, 2012

FDA has notified healthcare professionals that it is aware of a study published in the New England Journal of Medicine reporting a small increase in cardiovascular deaths and in the risk of death from any cause in persons treated with a 5-day course of azithromycin (Zithromax) compared to persons treated with amoxicillin, ciprofloxacin, or no drug.

FDA has notified healthcare professionals that it is aware of a study published in the New England Journal of Medicine (Azithromycin and the Risk of Cardiovascular Death) reporting a small increase in cardiovascular deaths and in the risk of death from any cause in persons treated with a 5-day course of azithromycin (Zithromax) compared to persons treated with amoxicillin, ciprofloxacin, or no drug.

Azithromycin belongs to a class of antibacterial drugs called macrolides, which have been associated with cardiovascular effects; specifically, prolongation of the QT interval.

In the NEJM article, researchers studied a Tennessee Medicaid cohort designed to detect an increased risk of death related to short-term cardiac effects of medication, excluding patients with serious noncardiovascular illness and person-time during and shortly after hospitalization. The cohort included patients who took azithromycin (347,795 prescriptions), propensity-score–matched persons who took no antibiotics (1,391,180 control periods), and patients who took amoxicillin (1,348,672 prescriptions), ciprofloxacin (264,626 prescriptions), or levofloxacin (193,906 prescriptions).

During 5 days of therapy, patients taking azithromycin, as compared with those who took no antibiotics, had an increased risk of cardiovascular death (HR=2.88; 95% CI, 1.79–4.63; PP=.002). Patients who took amoxicillin had no increase in the risk of death during this period. Relative to amoxicillin, azithromycin was associated with an increased risk of cardiovascular death (HR=2.49; 95% CI, 1.38–4.50; P=.002) and death from any cause (HR=2.02; 95% CI, 1.24–3.30; P=.005), with an estimated 47 additional cardiovascular deaths per 1 million courses; patients in the highest decile of risk for cardiovascular disease had an estimated 245 additional cardiovascular deaths per 1 million courses. The risk of cardiovascular death was significantly greater with azithromycin than with ciprofloxacin but did not differ significantly from that with levofloxacin.

FDA said that it is reviewing the results from this study and will communicate any new information on azithromycin and on this study or on the potential risk of QT interval prolongation after the agency has completed its review.

In 2011, FDA reviewed macrolide drug labeling information related to QT interval prolongation and TdP. The Warnings and Precautions section of the Zmax drug label (azithromycin extended release for oral suspension) was revised in March 2012 to include new information regarding risk for QT interval prolongation, which appears to be low. The drug labels for clarithromycin and erythromycin also contain information about QT interval prolongation in the Warnings section. FDA is in the process of updating risk information in the drug labels for additional macrolide antibacterial drugs.

FDA has recommended that patients taking azithromycin should not stop taking their medicine without talking to their healthcare professionals. Healthcare professionals should be aware of the potential for QT interval prolongation and heart arrhythmias when prescribing or administering macrolides.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to FDA's MedWatch Safety Information and Adverse Event Reporting Program in one of the following ways:

By completing and submitting the report online: www.fda.gov/MedWatch/report.htm; by choosing to download the form; or by calling 800-332-1088 to request a reporting form, and then completing and returning it to the address on the pre-addressed form or submitting it by fax to 800-FDA-0178.