Assessing the association between fluoroquinolones and emerging adverse drug reactions raised by regulatory agencies: An umbrella review

Milo Gatti; Matteo Bianchin; Emanuel Raschi; Fabrizio De Ponti

doi:10.1016/j.ejim.2020.01.009

Assessing the association between fluoroquinolones and emerging adverse drug reactions raised by regulatory agencies: An umbrella review

Eur J Intern Med. 2020 May:75:60-70. doi: 10.1016/j.ejim.2020.01.009. Epub 2020 Jan 23.

Authors

Milo Gatti¹, Matteo Bianchin¹, Emanuel Raschi², Fabrizio De Ponti¹

Affiliations

¹ Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Irnerio 48, 40126, Bologna, Italy.
² Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Irnerio 48, 40126, Bologna, Italy. Electronic address: emanuel.raschi@unibo.it.

PMID: 31983604
DOI: 10.1016/j.ejim.2020.01.009

Abstract

Background: Regulatory agencies warned against fluoroquinolones for the management of minor infections because of the risk of emerging adverse events (collagen-associated adverse events, neuropsychiatric toxicity and long-term disability). We aimed to assess quality and credibility of evidence as well as causality regarding these putative associations.

Methods: MEDLINE, Scopus, Web of Science and PROSPERO were searched, from inception to August 2019, for systematic reviews with meta-analyses investigating emerging adverse events. Two investigators extracted data to grade quality (through validated AMSTAR-2 tool), rank credibility of the evidence (convincing, highly suggestive, suggestive, weak) through adapted criteria including E-value calculation, and assess causality (Hill's criteria).

Results: Seven systematic reviews of observational studies providing 16 risk estimates [seven, five and four, respectively, for aortic aneurysm/dissection (AAD), retinal detachment (RD) and any tendon disorders (ATD)] met inclusion criteria. No systematic reviews with meta-analysis investigating the risk of neuropsychiatric toxicity or long-term disability were found. The associations between fluoroquinolones and AAD/ATD showed highly suggestive credibility and were supported by strong evidence of causality (double increased risk, especially within first 2 months of treatment). Conflicting data concerning the emergence of RD were retrieved, resulting in weak evidence of causality. Quality of the evidence ranged from high to low for AAD, from moderate to critically low for RD, and it was moderate for ATD.

Conclusion: Our analysis supports credible, plausible and highly suggestive associations with AAD (rare occurrence but strong causality) and ATD. Limitations of both umbrella reviews and observational evidence should be considered.

Keywords: Aortopathy; Credibility assessment; Emerging adverse events; Regulatory warnings; Systemic fluoroquinolones.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Drug-Related Side Effects and Adverse Reactions*
Fluoroquinolones* / adverse effects
Humans

Substances

Fluoroquinolones