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

Ashwini Sankar, Kristi M. Swanson, Jiani Zhou, Anupam Bapu Jena, Joseph S. Ross, Nilay D. Shah, Pinar Karaca Mandic

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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 1238397 unique patients with a total of 2720071 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..

Original languageEnglish (US)
Article numbere2136662
JournalJAMA Network Open
Issue number12
StatePublished - Dec 2 2021

Bibliographical note

Funding Information:
Funding/Support: This study was funded by grant R01 HS025164 from the Agency for Healthcare Research and Quality (AHRQ). Dr Jena was supported by grant 1DP5OD017897 from the Office of the Director, National Institutes of Health (NIH). Dr Ross was supported by grant R01HS022882 from the AHRQ and grant R01HL144644 from the National Heart, Lung and Blood Institute of the NIH (NHLBI/NIH). Dr Shah was supported by grants

Funding Information:
R01HS025402 and R03HS025517 from the AHRQ and grant R01HL131535 from the NHLBI/NIH. Dr Karaca-Mandic was supported by grant P01AG005842 from the National Institute on Aging and grant R56 HL130496 from the NIH.

Funding Information:
Author Contributions: Dr Sankar had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Sankar, Swanson, Zhou, Karaca-Mandic. Acquisition, analysis, or interpretation of data: Sankar, Zhou, Jena, Ross, Shah, Karaca-Mandic. Drafting of the manuscript: Sankar, Zhou. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Sankar, Zhou, Jena, Karaca-Mandic. Obtained funding: Karaca-Mandic. Administrative, technical, or material support: Swanson. Supervision: Karaca-Mandic. Conflict of Interest Disclosures: Ms Zhou reported being a research fellow at Medtronic outside the submitted work. Dr Jena reported receiving personal fees from Pfizer, Hill Rom Services, Bristol Myers Squibb, Eli Lilly, Vertex Pharmaceuticals, Tesaro, AstraZeneca, Bioverativ, Merck, Janssen, Edwards Life Sciences, Novartis, Amgen, Eisai, Otsuka, Celgene, Sanofi Aventis, Biogen, Precision Health Economics, and the Analysis Group outside the submitted work. Dr Ross reported receiving grants from the US Food and Drug Administration (FDA), Johnson & Johnson, the Medical Devices Innovation Consortium, and the Laura and John Arnold Foundation outside the submitted work. Dr Shah reported receiving grants from the FDA, the Center for Medicare and Medicaid Innovation, and the Patient Centered Outcomes Research Institute outside the submitted work. Dr Karaca-Mandic reported receiving grants from the American Cancer Society; receiving personal fees from Tactile Medical, Sempre Health, and Precision Health Economics; and holding an executive position at XanthosHealth LLC outside the submitted work. No other disclosures were reported.

Publisher Copyright:
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