PT  - JOURNAL ARTICLE
AU  - Gowtham A. Rao
AU  - Joshua R. Mann
AU  - Azza Shoaibi
AU  - Charles Lee Bennett
AU  - Georges Nahhas
AU  - S. Scott Sutton
AU  - Sony Jacob
AU  - Scott M. Strayer
TI  - Azithromycin and Levofloxacin Use and Increased Risk of Cardiac Arrhythmia and Death
AID  - 10.1370/afm.1601
DP  - 2014 Mar 01
TA  - The Annals of Family Medicine
PG  - 121--127
VI  - 12
IP  - 2
4099  - http://www.annfammed.org/content/12/2/121.short
4100  - http://www.annfammed.org/content/12/2/121.full
SO  - Ann Fam Med2014 Mar 01; 12
AB  - PURPOSE Azithromycin use has been associated with increased risk of death among patients at high baseline risk, but not for younger and middle-aged adults. The Food and Drug Administration issued a public warning on azithromycin, including a statement that the risks were similar for levofloxacin. We conducted a retrospective cohort study among US veterans to test the hypothesis that taking azithromycin or levofloxacin would increase the risk of cardiovascular death and cardiac arrhythmia compared with persons taking amoxicillin. METHODS We studied a cohort of US veterans (mean age, 56.8 years) who received an exclusive outpatient dispensation of either amoxicillin (n = 979,380), azithromycin (n = 594,792), or levofloxacin (n = 201,798) at the Department of Veterans Affairs between September 1999 and April 2012. Azithromycin was dispensed mostly for 5 days, whereas amoxicillin and levofloxacin were dispensed mostly for at least 10 days. RESULTS During treatment days 1 to 5, patients receiving azithromycin had significantly increased risk of death (hazard ratio [HR] = 1.48; 95% CI, 1.05–2.09) and serious arrhythmia (HR = 1.77; 95% CI, 1.20–2.62) compared with patients receiving amoxicillin. On treatment days 6 to 10, risks were not statistically different. Compared with patients receiving amoxicillin, patients receiving levofloxacin for days 1 to 5 had a greater risk of death (HR = 2.49, 95% CI, 1.7–3.64) and serious cardiac arrhythmia (HR = 2.43, 95% CI, 1.56–3.79); this risk remained significantly different for days 6 to 10 for both death (HR = 1.95, 95% CI, 1.32–2.88) and arrhythmia (HR = 1.75; 95% CI, 1.09–2.82). CONCLUSIONS Compared with amoxicillin, azithromycin resulted in a statistically significant increase in mortality and arrhythmia risks on days 1 to 5, but not 6 to 10. Levofloxacin, which was predominantly dispensed for a minimum of 10 days, resulted in an increased risk throughout the 10-day period.