Should We Stop Prescribing Azithromycin?

In 2011, Azithromycin was the seventh most prescribed (55.3 million prescriptions) medication according to IMS Health. There have been several publications indicating that the use of macrolide antibiotics increase risk of serious ventricular arrhythmias and sudden cardiac death (FDA Adverse Event Reporting System). Specifically, two recent studies in NEJM were published looking at the risk of Azithromycin with cardiovascular death and received lots of press recently.


Azithromycin and the Risk of Cardiovascular Death


What They Did:
  • Retrospective, Observational Cohort Study
  • Tennessee Medicaid Cohort
  • Compared
    • 1. No antibiotics (1,391,180 prescriptions)
    • 2. Azithromycin (347,795 prescriptions)
    • 3. Amoxicillin (1,348,672 prescriptions)
  • Detected an increased risk of death
Primary Outcomes:
  • Cardiovascular death
  • Death from any cause

  • Cardiovascular Risk Factors in This Study: Smoking, high BMI, poor diet, and low physical activity
  • NO statistically significant risk of death after the 5 day course of azithromycin completed
  • Observational, non-randomized clinical trial

During 5 days of azithromycin therapy, there is a small absolute increase in cardiovascular deaths and most pronounced in patients with a high baseline risk of cardiovascular disease.


What They Did:
  • Retrospective, Observational Cohort Study
  • Danish Adults
  • Compared
    • No antibiotics vs Azithromycin (1,102050 prescriptions compared in 1:1 ratio)
    • Azithromycin vs Pencillin V (1,102,419 prescriptions vs 7,364,292 prescriptions)
Primary Outcomes:
  • Cardiovascular Death
  • No increase in cardiovascular death with recent or past use of azithromycin
  • No increase in cardiovascular death in patients with no history of cardiovascular disease
  • There is an increase in cardiovascular death in patients with a history of cardiovascular disease
  • Did not have information of known risk factors for cardiovascular disease (smoking and BMI)
  • Number of events in the subgroup analysis is low

Azithromycin use is not associated with an increased risk of death from cardiovascular causes in a general population of young and middle-aged adults


In my opinion, how will this affect your practice?
  • In the second study the patient population had better cardiovascular health than the first study
  • The increased cardiovascular risk may be from the systemic infectious process and not azithromycin itself
  • You can still prescribe azithromycin, but remember the small increased risk of death in patients with cardiovascular disease



1. Ray WA et al. Azithromycin and the Risk of Cardiovascular Death. NEJM 2012: 366 (20); 1881 – 90. PMID: 22592294

2. Svanstrom H et al. Use of Azithromycin and Death from Cardiovascular Causes. NEJM 2013 May; 368 (18); 1704 – 1712. PMID: 23635050 _______________________________________________________________________________

Dr. Salim R. Rezaie is a physician at the University of Texas Health Science Center at San Antonio. He is double board-certified in Emergency Medicine and Internal Medicine.

About Salim Rezaie

Dr. Rezaie completed his medical school training at Texas A&M Health Science Center, and followed that up with a combined Emergency Medicine/Internal Medicine residency at East Carolina University in Greenville, NC. Currently, he is an attending on the faculty of UTHSCSA in San Antonio, TX, where he focuses on medical education, social media as a tool for education (FOAMed), and building the bridges between internal medicine, critical care, and emergency medicine. Feel free to contact him on Twitter (@srrezaie) (@UTHSCSAPearls) about anything EM/IM! Salim Rezaie
May 21, 2013

Dr. Rezaie, indeed a common debate in outpatient clinics: should we be prescribing azithromycin as much as we do? I’ve adopted the same approach as you outlined: we need to think twice before ordering azithromycin in patient with heart disease but overall the risk is not high.

May 21, 2013

Ravi, thank you for reading the post. This debate actually came up in the ED of all places between myself and another physician. The statement was made that we should not ever prescribe azithromycin with “all the new studies out.” I just wanted to look at the studies a little bit closer, and turns out in the general population no big deal, and pts with heart disease there is a small, but real increase in death. This still does not mean we cannot prescribe this to these patients, but we should think hard before prescribing it. Thank you again.


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