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Drug Safety

, Volume 13, Issue 6, pp 343–358 | Cite as

Tolerability of Fluoroquinolone Antibiotics

Past, Present and Future
  • Peter Ball
  • Glenn Tillotson
Review Article Drug Experience

Summary

New fluoroquinolones have been in clinical use for 10 years and have an excellent record of safety and tolerance. The main elements of their adverse reaction profile were predictable from human experience with precursor naphthyridines and quinolones, and from toxicological studies in animals. Thus gastrointestinal reactions (1 to 5%), skin disturbances (less than 2.5%) and central nervous system (CNS) effects (usually around 1 to 2%) were anticipated. Individual group members exhibit particular properties in relation to their chemical structures, for example the phototoxicity associated with 8-halogenation of the nucleus and found to be a particular problem with lomefloxacin and sparfloxacin. Other members, for example ofloxacin, are linked to a higher than usual incidence of CNS reactions and psychological disturbance. However, despite increasing usage, none of the present group have been implicated in joint damage in children, which had been a major concern following reports of this effect in juvenile animals in chronic toxicity studies. Furthermore, intravenous formulations appear to have no associated increase in toxicity. Crystalluria with associated renal damage, originally thought likely to limit intravenous dosage, has not proved to be a problem in humans. Clinically significant interactions may occur but, as with those involving various NSAIDs and potentially leading to convulsions, they have been defined and are thus avoidable.

Postmarketing surveillance studies and prescription event monitoring have largely confirmed the limited adverse reaction profile defined during clinical trials. However, some unexpected reactions have appeared after launch, most notably the episodes of haemolysis, renal failure and hypoglycaemia which led to the withdrawal of temafloxacin. These effects have not been observed with other fluoroquinolones. However, severe tendinitis appears to be a group effect, albeit rare, and anaphylactoid reactions have been reported with several of the fluoroquinolone group, often in AIDS patients.

The new fluoroquinolones are essentially a well tolerated group of antibacterials, the benefits of which clearly outweigh their disadvantages in a wide range of indications. Clinical efficacy has been a larger determinant of which members have succeeded in the marketplace than potential toxicity. However, the lesser potential for adverse effects of some of the class, e.g. norfloxacin, ofloxacin and ciprofloxacin, has undoubtedly led to their more widespread use. For others, e.g. enoxacin, limited clinical utility and a perception of increased toxicity have resulted in sidelining. There remains the potential for development of safer and yet more active fluoroquinolones via chemical manipulation both of the nucleus and the side chain substituents.

Keywords

Adis International Limited Ofloxacin Levofloxacin Norfloxacin Nalidixic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Adis International Limited 1995

Authors and Affiliations

  • Peter Ball
    • 1
  • Glenn Tillotson
    • 2
  1. 1.Infectious Diseases Unit (c/o Ward 7)Victoria HospitalKirkcaldy, FifeScotland
  2. 2.Bayer plcNewburyEngland

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