Azithromycin and the Heart: Where are we at in 2018?

Azithromycin: Are there any cardiac concerns?

Azithromycin is an antibiotic which is widely used to treat a variety of infections. It is sometimes used by hair loss specialists for treating folliculitis decalvans. In 2013, the Food and Drug Administration added a new warning to prescriptions for azithromycin (read FDA Warning). The warning stated that azithromycin has the potential to affect heart rhythms in some patients and even raised the possibility some of these could be fatal. Specifically, the FDA has updated azithromycin package labeling to include the risk of prolonged cardiac repolarization and QT prolongation, which increase the possibility of cardiac dysrhythmias and torsades de pointes, especially in older adults. Since that time, there has been intensive research looking at the cardiac side effects of azithromycin.

2018 Studies

A recent 2018 study by Hertz and colleagues identified over 29,000 patients with out of hospital cardiac arrest.   The researchers concluded that the risk of cardiac arrest during treatment with macrocodes (like azithromycin) was similar to that of penicillin V, suggesting that there was no additional risk associated with macrolides.

2017 Studies

A 2017 study by Sutton and colleagues evaluated over 283,743 prescriptions for azithromycin; 143,191 for amoxicillin; 52,714 for clindamycin; 38,133 for clarithromycin and 49,734 for the quinolone.  The authors concluded that odds of cardiovascular mortality between azithromycin and other antibiotics were not statistically significantly different and previous published findings may not be applicable to the general population.

In 2017, Quinn and colleagues examined over 39,000 patients who died suddenly while receiving digoxin. Their data analysis showed that there was no statistically significant increase in the risk of sudden death following treatment with any of the macrolide antibiotics (erythromycin, clarithvmycin, or azithromycin) compared to a comparison antibiotic cefuroxine. Again, these authors felt the these findings actually reinforced the cardiovascular safety of macrolide antibiotics in a high-risk population.

In 2017, Trifiro examined data from over 14 million antibiotic users. Their data showed that azithromycin use was associated with an increased risk of ventricular arrhythmia when compared with nonuse of antibiotics, but not when compared with current amoxicillin use. The decreased risk with an active comparator suggests significant confounding by indication.

2016 Studies

A large 2016 study of over 600,000 seniors by Trac and colleagues showed that cmpared with nonmacrolide antibiotics, macrolide antibiotics were not associated with a higher risk of ventricular arrhythmia. The authors concluded that among older adults, macrolide antibiotics were not associated with a higher 30-day risk of ventricular arrhythmia than nonmacrolide antibiotics. Moreover, the authors proposed that the current warnings from the US Food and Drug Administration may be overstated.  The authors concluded that these results were reassuring for health care providers who prescribe macrolide antibiotics to a wide range of patients in routine care. 

Conclusion

At present, we need to be aware for the FDA warming on azithromycin. However, we equally need to be aware of the abundant evidence that has arisen since that time of the original FDA warning which has provided further data. The current evidence would suggest that users of azithromycin are not an increased risk for ventricular arrhythmias compared to other antibiotics. For folliculitis decalvans, where a physician must often chose among antibiotics, there is no good evidence to suggest that use of azithromycin would put  patient at increased risk for serious heart rhythm abnormality compared to using another antibiotic.

REFERENCES

Sutton SS, et al. Appraisal of the cardiovascular risks of azithromycin: an observational analysis. J Comp Eff Res. 2017 Sep;6(6):509-517. 

Hertz FB, et al. Does macrolide use confer risk of out-of-hospital cardiac arrest compared with penicillin V? A Danish national case-crossover and case-time-control study.  BMJ Open. 2018.

Quinn KL, et al. Macrolides, Digoxin Toxicity and the Risk of Sudden Death: A Population-Based Study.  Drug Saf. 2017.

Trifirò G, et al. Use of azithromycin and risk of ventricular arrhythmia. CMAJ. 2017.

Sacks HS. In older adults, macrolide antibiotics were not linked to increased risk for ventricular arrhythmia.  Ann Intern Med. 2016.

Espadas D, et al. Lack of effect of azithromycin on QT interval in children: a cohort study. Arch Dis Child. 2016.

Trac MH, et al.  Macrolide antibiotics and the risk of ventricular arrhythmia in older adults. CMAJ. 2016.