Fluoroquinolone-Associated Tendon-Rupture: A Summary Of Reports In The Food And Drug Administration's (Fda's) Adverse Event Reporting System

Tendon rupture is associated with fluoroquinolones and listed in boxed warnings. We reviewed and summarized reports of tendon rupture associated with fluoroquinolones as reported in the FDA’s Adverse Event Reporting System (FAERS) through September 26, 2012. We queried the FAERS for reports of tendon rupture involving each fluoroquinolone. Signal detection consisted of empiric Bayes geometric mean (EBGM), with 95% confidence intervals from initial marketing date for each drug. For a signal to be considered significant, minimum criteria are: reports of 3 or more cases, the low end of the 95% confidence interval must be 2.0 or greater. There were 2539 tendon rupture cases. Most cases were reported with levofloxacin (61.25%) followed by ciprofloxacin (23.87%) and moxifloxacin (9.05%). Signal detection results for fluoroquinolones were: ciprofloxacin (EBGM=20.0, 95%CI= 18.2-21.6), enoxacin (EBGM=13.2, 95%CI= 4.2-29.7), gatifloxacin (EBGM=5.0, 95%CI= 3.5-7.0), levofloxacin (EBGM=55.2, 95%CI= 52.3-58.0), moxifloxacin (EBGM=13.3, 95%CI= 11.7-15.1), norfloxacin (EBGM=9.6, 95%CI= 6.5-13.5), ofloxacin (EBGM=8.2, 95%CI= 6.3-10.2), gemifloxacin (EBGM=1.9, 95%CI= 0.7-4.5), lomefloxacin (EBGM=2.3, 95%CI=0.94-5), and trovafloxacin (EBGM=0.3, 95%CI= 0.08-1.1). FAERS event date timelines suggest lower risk of tendon rupture for gemifloxacin (n=5), lomefloxacin (n=5), and trovafloxan (n=1), with initial reports in 2006, 2005, and 2000, respectively. The mean age was 59.6± 5.1. The most common concurrent drugs were corticosteroids (levofloxacin=27.1%, enoxacin = 20%, gatifloxacin =18.2%, moxifloxacin =14.7%, ciprofloxacin = 10.4%, ofloxacin =5.3%, and norfloxacin = 2.4%). Analysis by the reporting country revealed that most cases were reported from the US(70%) followed by Japan(8.2%), Great Britain(3.7%), France(.9%) and Canada(.42%). Tendon rupture was reported with most fluoroquinolones. Significant signals existed for all flouroquinolones except gemifloxacin, lomefloxacin, and trovafloxacin, which potentially have lower risks. However, FAERS data are dependent upon utilization and MedWatch reporting rates. As stated in the boxed warning, as stated in the boxed warning, concurrent corticosteroids increases risk of tendon rupture.