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Fluoroquinolone-Associated Myasthenia Gravis Exacerbation

Evaluation of Postmarketing Reports from the US FDA Adverse Event Reporting System and a Literature Review

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Abstract

Background: Exacerbations of myasthenia gravis have been reported in antibacterial-treated patients. In animal and in vitro models of experimentallyinduced myasthenia gravis, fluoroquinolones exhibit neuromuscular blockade.

Objective: The aim of this retrospective study was to evaluate postmarketing adverse event reports submitted to the US FDA and case reports published in the scientific literature for a potential association between fluoroquinolone exposure and acute exacerbations of myasthenia gravis.

Methods: On 1 March 2011, we searched the FDA Adverse Event Reporting System (AERS) database to retrieve all reports of myasthenia gravis exacerbation as a serious adverse event in patients treated with fluoroquinolones. We also conducted an Internet-based search using EMBASE for additional English-language cases in the scientific literature.

Results: We identified a total of 37 unique cases describing myasthenia gravis exacerbation following fluoroquinolone systemic exposure. We retrieved AERS reports for 27 non-ventilated patients administered the following fluoroquinolones: levofloxacin (n = 9), moxifloxacin (n = 6), ciprofloxacin (n=6), ofloxacin (n = 2), gatifloxacin (n = 2), norfloxacin (n=1) and trovafloxacin (n= 1). Additionally, we retrieved ten case reports published in the literature involving non-ventilated patients administered ciprofloxacin (n = 4), levofloxacin (n = 2) and ofloxacin, norfloxacin, pefloxacin and prulifloxacin (1 patient each). Myasthenia gravis exacerbations developed a median of 1 day following fluoroquinolone exposure. The 37 cases describe dyspnoea (n= 19; 51%), myasthenic crisis requiring ventilatory support (n= 11; 30%) and death (n = 2; 5%). Additional exacerbation-related adverse events were generalized muscle weakness (n = 20; 54%), dysphagia (n = 9; 24%), diplopia (n= 6; 16%) and ptosis (n = 6; 16%). Six patients (16%) experienced a positive rechallenge, with recurrent myasthenia gravis exacerbation after fluoroquinolone reintroduction.

Conclusions: Fluoroquinolone exposure may result in potentially life-threatening myasthenia gravis exacerbations in patients with underlying disease. Healthcare professionals should be aware of this serious drug-disease association and carefully weigh the benefit-risks of fluoroquinolones when treating infections in non-ventilated myasthenic patients.

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Acknowledgements

No sources of funding were used to conduct this study or prepare this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this study.

The views expressed are those of the authors and do not necessarily represent the views of the FDA.

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  1. US Food and Drug Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology, Division of Pharmacovigilance II, 10903 New Hampshire Ave, Bldg 22 Rm 3464, Silver Spring, MD, 20993, USA.

    S. Christopher Jones, Alfred Sorbello & Robert M. Boucher

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  1. S. Christopher Jones
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  2. Alfred Sorbello
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  3. Robert M. Boucher
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Jones, S.C., Sorbello, A. & Boucher, R.M. Fluoroquinolone-Associated Myasthenia Gravis Exacerbation. Drug-Safety 34, 839–847 (2011). https://doi.org/10.2165/11593110-000000000-00000

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