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FDA warns of potentially fatal heart rhythm associated with azithromycin
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The FDA has warned that the antibiotic azithromycin can potentially cause a fatal arrhythmia, according to a safety announcement issued today.
Patients who are especially at risk include those with risk factors such as existing QT interval prolongation, low blood levels of potassium or magnesium, a slower than normal heart rate or use of drugs to treat abnormal heart rhythms. A study published last year in The New England Journal of Medicine suggested that the excess risk for cardiovascular death related to azithromycin (Zithromax, Pfizer) was approximately 1 in 4,100 among high-risk patients, according to the announcement.
The FDA has mandated that all drug labels for azithromycin be updated so that the Warnings and Precautions section contain information on this risk. They advise health care professionals to consider the risk for fatal heart rhythm when considering azithromycin treatment for patients at risk for cardiovascular events.
“The potential risk of QT prolongation with azithromycin should be placed in appropriate context when choosing an antibacterial drug,” the FDA wrote in the safety announcement.
“Alternative drugs in the macrolide class, or non-macrolides such as the fluoroquinolones, also have the potential for QT prolongation or other significant side effects that should be considered when choosing an antibacterial drug.”
Perspective
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Thomas M. File, Jr., MD, MSc, MACP, FIDSA, FCCP
This issue has caused a lot of media buzz and I have had several colleagues ask me about this. Firstly, it is important to acknowledge (as listed in the FDA Data Summary) several limitations of the NEJM article that prompted the FDA review: Not a randomized study and despite attempts at adjusting, there is risk for confounding; only evaluated outpatients; and deaths were determined by death certificates rather than medical records. However, the FDA review has concluded that the overall methodology of the study and the results of a clinical QT study conducted by the manufacturer support the validity of the finding. Thus, the concern for proarrythmia due to QT prolongation is associated with the two primary regimens of choice for empirical therapy of CAP: Respiratory fluoroquinolones and macrolide plus beta-lactam. My personal take is that from a risk/benefit basis, I still feel that combination therapy with azithromycin is appropriate for serious pneumonia (requiring admission) and especially for those with severe CAP (ICU) where many studies (mostly observational) have shown a benefit for macrolides, mostly azithromycin plus beta-lactam. In addition, as I review the NEJM article, I am interpreting that the majority of patients assessed in the Tennessee database had non-pneumonia uses as 63% of patients were treated for ‘ear, nose, throat or bronchitis.’ Thus, I wonder how many of these really warranted antimicrobial therapy at all. However, because of this finding and alert I am more concerned with screening of patients for heart disease — especially QT effect. For patients with known QT interval prolongation or risk factors for QT interval prolongation, we now favor doxycycline since it has not been associated with QT interval prolongation. Risk factors for QT interval prolongation include hypokalemia, hypomagnesemia, clinically significant bradycardia and the use of other agents that prolong the QT interval, including class IA (quinidine, procainamide) and class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents and certain azoles (voriconazole, posaconazole).
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