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Safety Profile of the Respiratory Fluoroquinolone Moxifloxacin

Comparison with Other Fluoroquinolones and Other Antibacterial Classes

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Abstract

Moxifloxacin, a fluoroquinolone with potent activity against respiratory pathogens, is approved and considered as an alternative to β-lactams and macrolides for the treatment of acute bacterial sinusitis and lower respiratory tract infections. In this review, we critically examine its safety profile in comparison with other fluoroquinolones and other antibacterial classes sharing similar indications. Data were extracted from published clinical trials, meta-analyses, postmarketing studies, spontaneous report systems and case reports for rare effects.

Global analysis did not reveal significantly higher incidences of drug-related adverse effects than for comparators. Tendon rupture was infrequent with moxifloxacin, including when used in elderly patients with chronic obstructive pulmonary disease. Severe toxic cutaneous reactions and allergies were very rare. Phototoxicity and CNS adverse effects were less common than with other fluoroquinolones. Although causing a 4–7 msec corrected QT interval prolongation, severe cardiac toxicity was neither seen in large cohorts or clinical trials nor reported to pharmacovigilance systems. Hepatotoxicity was not different from what was observed for other fluoroquinolones (excluding trovafloxacin) and less frequent than reported for amoxicillin-clavulanic acid or telithromycin.

The data show that using moxifloxacin, in its accepted indications and following the corresponding guidelines, should not be associated with an excessive incidence of drug-related adverse reactions, provided the clinician takes care in identifying patients with known risk factors and pays due attention to the contraindications and warnings mentioned in the labelling.

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Notes

  1. 1The structural formulae of all fluoroquinolones mentioned in this review, together with general considerations on structure-toxicity relationships, can be found elsewhere (see Van Bambeke et al.[3])

  2. 2The original search was performed in April 2008 with no date limit, and repeated in November 2008 to capture additional references; at manuscript proof stage (21 March 2009) a new search covering the whole of 2008 to March 2009 was again performed using ‘(moxifloxacin OR levofloxacin) AND (adverse effect OR safety OR cardiac OR hepatic OR toxicity OR QTc OR tendon* OR photoxicity OR death)’ as boolean operators to retrieve the very last publications relevant to moxifloxacin and levofloxacin.

  3. 3Moxifloxacin and levofloxacin, as well as all other fluoroquinolones currently approved in Europe, have been registered through decentralized or national procedures, making it difficult to compare and analyze the individual drug labels. An analysis of recent decisions of the European Medicines Agency about moxifloxacin and an update of its labeling, which will apply to countries of the EU, is presented in section 3 in this review.

  4. 4Moxifloxacin is often used in phase I trials as a ‘positive’ control for corrected QT (QTc) interval prolongation, which has led to the erroneous conclusion that the drug causes a potential hazard in patients. However, the reason that moxifloxacin is used is because the drug produces a measurable QTc interval increase; this allows the method used to assess QT interval prolongation to be validated while avoiding significant health risk for study subjects.

  5. 5Moxifloxacin was registered in Europe through a decentralized procedure. The amended labelling will be put into effect and made available in each Member country starting in 2009.

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Acknowledgements

We thank Professor P. Ball (School of Biomedical Sciences, St Andrews University, St Andrews, Fife, UK) for critical reading of this review. Françoise Van Bambeke is Maître de recherches of the Belgian FondsdelaRecherche Scientifique. Both authors are members of the Belgian Advisory Board of Bayer-Belgium. No sources of funding were used to assist in the preparation of this review.

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  1. Unité de pharmacologie cellulaire et moléculaire & Centre de Pharmacie Clinique, Louvain Drug Research Institute, Université catholique de Louvain, UCL7370 avenue Mounier 73, 1200, Brussels, Belgium

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Van Bambeke, F., Tulkens, P.M. Safety Profile of the Respiratory Fluoroquinolone Moxifloxacin. Drug-Safety 32, 359–378 (2009). https://doi.org/10.2165/00002018-200932050-00001

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