Outpatient Fluoroquinolone Prescription Fills in the United States, 2014-2020: Assessing the Impact of Food and Drug Administration Safety Warnings

Background: The impact of United States (US) Food and Drug Administration (FDA) safety warnings on outpatient fluoroquinolone use is unclear. Methods: Annual changes in outpatient ciprofloxacin, levofloxacin and moxifloxacin prescription fills (IQVIA National Prescription Audit databases) were assessed using a regression model. Monthly fills during baseline (August 2014–April 2016), first (May 2016–June 2018), and second FDA warning periods (July 2018–February 2020) were compared by interrupted time series analysis. Results: From 2015 through 2019, total fluoroquinolone fills decreased from 35,616,786 (111.1/1000 persons) to 21,100,050 (64.3/1000 persons) annually (10.8% annually (P=0.001)). Ciprofloxacin, levofloxacin, and moxifloxacin fills decreased annually by 10.4% (P=0.001), 11.2% (P<0.001), and 17.7% (P=0.008), respectively. During the baseline period, there was no significant change in monthly fluoroquinolone fills. In May 2016 and during the first warning period, monthly fluoroquinolone fills decreased significantly (P-values<0.001); the trend of decreased fills was significantly greater than that of the baseline period (P=0.02). There was no change in fluoroquinolone fills in July 2018. Monthly fills decreased significantly throughout the second warning period (P<0.001), but the trend did not differ from that of the first warning period. Trends for ciprofloxacin, the most commonly prescribed fluoroquinolone, were similar to those for the class. Fills of prescriptions by infectious diseases specialists (P<0.005) and nurse practitioners (P=0.04) significantly increased during the study. Conclusions: US outpatient fluoroquinolone prescription fills significantly decreased from August 2014-February 2020, most strongly in association with May 2016 FDA warnings. FDA safety warnings are useful tools for leveraging outpatient antimicrobial stewardship.