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. 2021 Jun 1;181(6):808-816.
doi: 10.1001/jamainternmed.2021.1154.

Association of US Food and Drug Administration Removal of Indications for Use of Oral Quinolones With Prescribing Trends

Phuong T Tran  1   2 , Patrick J Antonelli  3   4 , Juan M Hincapie-Castillo  1   3 , Almut G Winterstein  1   3   5
Affiliations

Association of US Food and Drug Administration Removal of Indications for Use of Oral Quinolones With Prescribing Trends

Phuong T Tran et al. JAMA Intern Med. .

Abstract

Importance: In May 2016, due to concerns of the risks outweighing the benefits, the US Food and Drug Administration (FDA) removed systemic quinolones' indications for acute, uncomplicated urinary tract infection (uUTI), acute sinusitis (AS), and acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). How the change influenced oral quinolone use is unknown.

Objective: To assess the association of oral quinolone safety warnings and indication restrictions with use.

Design, setting, and participants: This interrupted time series (January 2015-November 2018) analysis of the monthly prevalence of oral quinolone-treated infection episodes used a national sample of privately insured patients in outpatient care from the IBM MarketScan Database and included adults with antibiotic treatment of new uUTI, AS, or AE-COPD episodes, excluding patients with conditions that complicate infections, previous hospitalization, or other infections.

Exposures: Time before and after May 2016 when the FDA mandated label changes.

Main outcomes and measures: Monthly oral quinolone use prevalence by each condition before and after the label changes, overall and stratified by prescriber specialty.

Results: In January 2015, quinolone prevalence among antibiotic-treated uUTI episodes (n = 652 235) was 41.6% (95% CI, 40.6%-42.5%); AS (n = 1 742 248) was 8.3% (95% CI, 7.9%-8.6%), and AE-COPD (n = 22 817) was 31.9% (95% CI, 30.3%-33.4%). Before the label changes, trends in monthly quinolone prevalence were nearly flat. The month of the label changes we noted an immediate reduction for uUTI (-7.2%; 95% CI, -8.6% to -5.8%); and to a lesser extent for AS (-1.2%; 95% CI, -1.5% to -0.9%) and AE-COPD (-2.6%; 95% CI, -4.1% to -1.1%), and continued monthly declines thereafter. Falsification tests confirmed an immediate decrease after the label change of quinolone use for uUTI but more obscured effects for AS and AE-COPD. Treatment shifted mostly to first-line (eg, nitrofurantoin in uUTI, amoxicillin in AS, macrolides in AE-COPD) and other second-line agents but use of not recommended antibiotics also increased (eg, tetracyclines in AE-COPD). Prescribing preferences varied, but significant reductions were seen across all prescriber specialties. At the end of the study period, quinolone was used for 19.2% of treated uUTIs, 2.9% of treated AS, and 14.6% of treated AE-COPD episodes.

Conclusions and relevance: Label changes and their announcements was associated with an immediate reduction in oral quinolone use for uUTI and to a lesser extent for AS and AE-COPD. Quinolones continued to contribute a considerable proportion of treatments for uUTI and AE-COPD episodes at the end of the study period, pointing to opportunities for further improvement.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Winterstein reported personal fees from the US Food and Drug Administration (FDA). She served on the FDA Advisory Committee that voted on the removal of the studied quinolone indications. She also reports grants during the conduct of the study from Merck, Sharp & Dohme unrelated to this work, and grants from the National Institutes of Health, FDA, State of Florida unrelated to this work, and personal fees from Arbor Pharmaceuticals unrelated outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Association of Label Changes With Oral Quinolone Use by Medical Condition (Interrupted Time Series Analysis)
UTI Indicates urinary tract infection; COPD, chronic obstructive pulmonary disease. Data points represent monthly prevalence of oral quinolone use between January 2015 and November 2018. The vertical dashed lines indicate May 2016 when US Food and Drug Administration (FDA) required quinolone label changes. Grey areas show the period from November 2015 (FDA advisory committee meeting) to July 2016 (FDA-approved label changes submitted by pharmaceutical companies). Regression lines show the trends of oral quinolone use before (blue lines) and after (orange lines) label changes. Dashed regression lines (blue) are the predicted trends of oral quinolone use after May 2016 assuming no changes in prelabel change trends.
Figure 2.
Figure 2.. Trends in Oral Antibiotic Use Prevalence by Medical Condition
UTI Indicates urinary tract infection; COPD, chronic obstructive pulmonary disease.
See this image and copyright information in PMC

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