Fluoroquinolones: old drugs, putative new toxicities

ABSTRACT

Introduction

Fluoroquinolone (FQ) antibiotics were approved in 1986 for treatment of urinary tract infections, sinusitis, and bronchitis. Numerous putative FQ-associated adverse events have been recently reported.

Areas covered

We review international regulatory agency experience with these FQ-associated toxicities. A 2015 FDA Advisory Committee meeting led regulatory agencies in Canada, Australia, the European Union, New Zealand, and Japan between 2017 and 2021 to evaluate FQ-associated long-term disability and aortic aneurysm/dissections. Regulatory agency guidance in the United States in 2016 warn that FQs should not be used as first-line therapies for urinary tract infections, sinusitis, and bronchitis if other antibiotics are available because of potential long-term and disabling toxicity. Regulatory agencies in European Union countries warn that FQs should not be used to treat mild infections. Product labels in Australia, New Zealand, Japan, and Canada do not have warnings related to FQ-associated disability. Revised product labels and public health advisories in the United States, the European Union, and Japan warn against FQ administration to persons at aortic aneurysm/dissection risks, while product labels and regulatory agency notifications from Canada, Australia, and New Zealand do not include these warnings.

Expert opinion

Harmonization of warnings related to FQ-associated disability in particular should be considered.

KEYWORDS:

• Adverse drug reactions
• fluoroquinolones-associated disability
• fluoroquinolones
• drug policy

Article highlights

• This manuscript critically reviews the most up-to-date knowledge on the safety profile of fluoroquinolones

• In this review, primary research articles on putative mechanisms of long-term toxicity associated with fluoroquinolone use are detailed

• The literature discussed herein led to evidence-based policy changes and periodic safety updates on these drugs

• The evidence-based policies and practices adopted are discussed and compared among different regulatory agencies

• Comparison of the different responses by regulatory agencies in the United States, Canada, European Union, Japan, Australia, and New Zealand highlight the need for harmonization of product labels and warnings going forward to reduce unnecessary antibiotic use.

This box summarizes key points contained in the article.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

CL Bennett, L Martin, C Bove and RA Baldock performed literature search and wrote the first draft. All authors revised the final draft. CL Bennett provided funding acquisition.

Additional information

Funding

This work received support from the National Cancer Institute (1R01 CA102713; CLB/OC), https://www-nih-gov.pallas2.tcl.sc.edu/about-nih/what-we-do/nih-almanac/national-cancer-institute-nci and a Royal Society grant (grant number RGS\R2\192126; CLB/OC).