The Medical Letter on Drugs and Therapeutics
In Brief: Safety of Azithromycin
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Recently published results of a large, carefully conducted retrospective study indicated that use of the antibiotic azithromycin (Zithromax, and others) may increase the risk of cardiovascular death, especially in patients with a high baseline risk of cardiovascular disease.1 One possible mechanism is prolongation of the QT interval, which is known to occur rarely with azithromycin and more frequently with the other macrolide antibiotics erythromycin (Erythrocin, and others) and clarithromycin (Biaxin, and others).

Among the patients who received 347,795 prescriptions for azithromycin, there were 29 cardiovascular deaths, a significantly higher rate than the 42 that occurred among the patients who received 1,348,672 prescriptions for amoxicillin (which does not prolong the QT interval) or the 41 that occurred among the 1,391,180 patients who took no antibiotics. Among patients with the highest baseline risk of cardiovascular disease, treatment with azithromycin, compared to amoxicillin, would have resulted in 245 additional cardiovascular deaths per million courses of the antibiotic.

As with any retrospective study, there could have been some undetected differences between the patients who received one drug or the other, but use of an appropriate non-macrolide alternative2 instead of azithromycin might be reasonable in patients with cardiovascular disease or in those who are taking other drugs that can prolong the QT interval (

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