A Reappraisal of Quinolone Tolerability The Experience of their Musculoskeletal Adverse Effects

Abstract

The experience of the rheumatological adverse effects of fluoroquinolones should be helpful for both toxicologists and epidemiologists. In the case of fluoroquinolone-related arthropathy, the paediatric clinical experience seems to support the possible use of newer derivatives like ciprofloxacin in children who really need it. This therapeutic attitude is still contradictory to the labelling of fluoroquinolones. Inversely, there has been an important time-lag between the first reports of fluoroquinolone-related tendinopathies and the official recognition of this unusual toxic phenomenon. This delay, along with the widespread use of fluoroquinolones, makes it difficult to return to more reasonable prescribing guidelines for these very useful and effective anti-microbial compounds. The reasons why potentially serious adverse effects of fluoroquinolones were not anticipated before their commercialisation may be related to the lack of adequate in vitro and in vivo models, and the unexpectedness of the events. When it occurs, fluoroquinolone-induced arthropathy is most frequently benign, and heals without sequelae. The prognosis is not so favourable in the case of fluoroquinolone-related tendinopathy, which carries an important risk of immediate or secondary tendon rupture. Increasingly, fluoroquinolones are being prescribed for benign infections of the urinary or bronchopulmonary tracts. Sometimes, they are even used for antimicrobial prophylaxis before surgical or endoscopic procedures. We believe that for any prescription, the risk/benefit ratio of the fluoroquinolones should be carefully considered, since better tolerated, less expensive drugs can usually be prescribed. Clear information dedicated both to physicians and patients regarding the cautions for use and possible adverse effects of fluoroquinolones would help reduce the risk and severity of adverse reactions. This is especially important for phototoxicity, tendinopathy and cardiovascular adverse effects. As underlined by Ball and Tillotson in this issue, the future clinical use of the fluoroquinolones will be determined by the balance between the antibacterial efficacy and adverse effects of these agents. The adverse reactions affecting the musculoskeletal system provide a good example of this dilemma. Given the absence of an adequate model of tendinopathy and the poor predictivity of animal manifestations in arthropathy and cartilage lesions in humans, careful monitoring of patients during phase II and III trials and, more importantly, long term pharmacovigilance during the postmarketing period, are still strongly warranted.