Azithromycin with QT-prolonging drugs may elevate cardiac event risk
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According to findings published in JAMA Network Open, the combination of azithromycin and QT-prolonging drugs was associated with a 40% increase in cardiac events compared with amoxicillin and QT-prolonging drugs.
However, in a large cohort, there was no difference between use of azithromycin and amoxicillin in risk for cardiac events, researchers reported.
“In this large cohort study including more than 4 million episodes of both azithromycin and amoxicillin use, we found no increased odds of cardiac events with azithromycin in the overall cohort but a significantly higher odds among patients prescribed concurrent QT-prolonging drugs with azithromycin,” Haridarshan Patel, PharmD, PhD, researcher in the department of pharmacy systems, outcomes and policy in the College of Pharmacy at the University of Illinois at Chicago, and colleagues wrote. “Alternative antibiotic therapies should be considered among these patients.”
For this retrospective study, investigators identified 4,282,570 episodes (mean age, 36 years; 53% women) of azithromycin or amoxicillin initiation using the Truven Health Analytics MarketScan database. Researchers compared the odds of cardiac events among new users of azithromycin compared with new users of amoxicillin at 5, 10 and 30 days after drug initiation. The primary outcome was hospitalization for cardiac events, including syncope, palpitations, ventricular arrhythmias, cardiac arrest or death.
Within 5 days after antibiotic initiation, cardiac events occurred in 0.03% of the overall cohort, the most frequent events being syncope (70%) and palpitations (22.5%).
Investigators found that the odds of cardiac events among patients taking azithromycin were not significantly higher compared with amoxicillin at 5 days (OR = 1.08; 95% CI, 0.98-1.2), 10 days (OR = 1.05; 95% CI, 0.97-1.15) or 30 days (OR = 0.98; 95% CI, 0.92-1.04) after initiation.
However, concurrent use of QT-prolonging drugs with azithromycin was associated with a significant increase in cardiac events compared with use of such drugs with amoxicillin (OR = 1.4; 95% CI, 1.04-1.87).
The most common QT-prolonging drugs taken among patients in this cohort included antidepressants (7.3%), opiate agonists (2.3%) and diuretics (1.9%).
“With the current pandemic situation, azithromycin, combined with hydroxychloroquine and other agents, is being used to treat patients with COVID-19,” Patel told Healio. “Our findings suggest using azithromycin combined with other QT-prolonging drugs such as the anti-malaria drug puts patients at high risk of developing serious cardiac events. Such patients should be closely monitored.
“There are over 200 drugs that have been associated with prolonging the QT interval, which may, in rare situations, lead to serious cardiac events,” Patel said in an interview. “There are over millions of patients who are prescribed azithromycin yearly. The risk of a cardiac event among such patients is a serious concern. Clinicians, especially pharmacists, should consider alternative therapies for patients at high risk of developing such events.”
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