The FDA has issued a safety alert on the antibiotic azithromycin (AKA Zithromax, Zmax, Z-Pack), after a review sparked by a study from May of last year, published in the New England Journal of Medicine. The FDA is now warning that azithromycin “may lead to a potentially fatal irregular heart rhythm,” but also acknowledges that the antibacterial is just joining a longer list of drugs with cardiac side effects to be weighed carefully before prescription.
Azithromycin, the NEJM study’s authors concluded, tripled the risk of heart death compared to patients not taking antibiotics at all, and doubled the risk compared to patients who were prescribed amoxicillin. But the risk was not the same for everyone. The study found that:
A 5-day course of azithromycin therapy, as compared with the first 5 days of a course of amoxicillin therapy, was associated with significant increases in the risk of both cardiovascular death (hazard ratio, 2.49; 95% CI, 1.38 to 4.50; P=0.002) and death from any cause (hazard ratio, 2.02; 95% CI, 1.24 to 3.30; P=0.005). Thus, patients who took azithromycin had an estimated 47 additional cardiovascular deaths per 1 million 5-day courses of therapy.
Five times that number were reported in patients who were at-risk for heart disease, for a chance of 1-in-4,100.
Patients with “known risk factors such as existing QT interval prolongation, low blood levels of potassium or magnesium, a slower than normal heart rate, or use of certain drugs used to treat abnormal heart rhythms, or arrhythmias,” warns the FDA, should avoid taking azithromycin where possible. (That said, azithromycin is commonly prescribed to patients with chronic obstructive pulmonary disease (COPD) or pneumonia, which have substantial risks of their own.)
The warning over azithromycin is not just because it may provoke cardiac arrhythmias, but because the arrhythmias it provokes result in sudden death. The technical name is torsades de pointes (referring to the look of the lines on an ECG). Torsades results from a prolongation of the QT interval, which is “the time from the onset of the electrical wave in the heart to when the entire heart has reset and is ready for the next beat.” That QT interval can be increased by medications that block potassium, for instance, a useful or harmful thing depending on the circumstances.
If torsades de pointes degenerates into ventricular fibrillation, death can result in minutes. Given the statistical evidence, though it’s not known precisely how azithromycin might be prolonging the QT interval, it seems worth reaching for a different antibiotic, especially if it’s for something on the order of an ear infection.
