Association of Fluoroquinolone Prescribing Rates With Black Box Warnings from the US Food and Drug Administration

JAMA Netw Open. 2021 Dec 1;4(12):e2136662. doi: 10.1001/jamanetworkopen.2021.36662.


Importance: In 2013 and 2016, the US Food and Drug Administration (FDA) issued warnings and recommended limited use of fluoroquinolones for patients with certain acute conditions. It is not clear how prescribers have responded to these warnings.

Objective: To analyze changes in prescribing of fluoroquinolones after the 2013 and 2016 FDA warnings and to examine the physician characteristics associated with these changes.

Design, setting, and participants: This cross-sectional study used Medicare administrative claims data on Medicare fee-for-service beneficiaries and OneKey data on physicians and their organizations from January 1, 2011, to December 31, 2017. The sample was restricted to outpatient visits for sinusitis, bronchitis, and uncomplicated urinary tract infections. An interrupted time series approach was used to analyze the changes in the prescription rate after each FDA warning. Data analysis was performed between January 1, 2011, and December 31, 2017.

Interventions: Two FDA black box warnings released in August 2013 and July 2016.

Main outcomes and measures: The main outcome was an indicator for fluoroquinolone prescriptions in 3 periods: before the 2013 warning (baseline period), after the 2013 warning but before the 2016 warning (postwarning period 1), and after the 2016 warning (postwarning period 2).

Results: The sample comprised 1 238 397 unique patients with a total of 2 720 071 outpatient acute care visits. Of this sample, 848 360 were women (68.5%), and the mean (SD) age was 69.7 (12.6) years. The immediate prescribing levels of fluoroquinolones in postwarning period 1 increased by 3.42 percentage points (95% CI, 3.23-3.62; P < .001) and declined by -0.77 percentage points (95% CI, -1.00 to -0.54; P < .001) in postwarning period 2. The prescribing trend increased by 0.08 percentage points per month (95% CI, 0.08-0.10; P < .001) in postwarning period 1 and 0.06 percentage points per month (95% CI, 0.04-0.08; P < .001) in postwarning period 2. In postwarning period 1, the prescribing levels for physicians who were affiliated with hospitals with a top 10th percentile case mix index vs those without such affiliation decreased by -1.13 percentage points (95% CI, -1.92 to -0.34; P = .005), whereas the levels for primary care physicians declined by -1.34 percentage points (95% CI, -1.78 to -0.88; P < .001) compared with non-primary care physicians in postwarning period 2. Physicians at teaching hospitals were the only ones who showed a decline in prescribing trend in postwarning period 1.

Conclusions and relevance: This cross-sectional study found an overall decline in prescribing of fluoroquinolones after the release of FDA warnings. Understanding the association of physician and organizational characteristics with fluoroquinolone prescribing behavior may ultimately help to identify mechanisms to improve de-adoption.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Ambulatory Care / statistics & numerical data*
  • Anti-Bacterial Agents / therapeutic use*
  • Bronchitis / drug therapy
  • Cross-Sectional Studies
  • Drug Labeling / legislation & jurisprudence
  • Drug Prescriptions / statistics & numerical data*
  • Female
  • Fluoroquinolones / therapeutic use*
  • Health Plan Implementation
  • Humans
  • Interrupted Time Series Analysis
  • Male
  • Medicare
  • Middle Aged
  • Practice Patterns, Physicians' / statistics & numerical data*
  • Sinusitis / drug therapy
  • United States
  • United States Food and Drug Administration
  • Urinary Tract Infections / drug therapy


  • Anti-Bacterial Agents
  • Fluoroquinolones