Toxicity of quinolones

Abstract

Reactions of the gastrointestinal tract, the CNS and the skin are the most often observed adverse effects during therapy with fluoroquinolones. At least for some of the newer fluoroquinolones a steep dose-response relationship of adverse effects seems to exist. Pathogenesis of the neurotoxic effects of fluoroquinolones is still unknown. Among the newer drugs, trovafloxacin caused mild CNS reactions such as dizziness and lightheadedness in a considerable proportion of patients. Young females seem to be especially sensitive to this effect, which diminishes during treatment or if taken together with food. Cardiotoxic potentials of sparfloxacin and grepafloxacin are higher than those of other fluoroquinolones, but during therapy no clearcut drug-related serious reactions have been reported, apart from a slight prolongation of the QT interval. However, to avoid risks these drugs should not be prescribed to patients with known prolongation of the QT interval (e.g. patients on antiarrhythmics). Phototoxicity has been described for all quinolones, but derivatives with a halogen atom at position 8 show the highest potential for such reactions. Fleroxacin, sparfloxacin, clinafloxacin and lomefloxacin belong to this group of fluoroquinolones. The phototoxic potential of the other new fluoroquinolones is considerably lower, but extensive exposure to UV light should generally be avoided during therapy with all quinolones. Chondrotoxicity of quinolones, as observed in immature animals, can affect articular cartilage and/or the epiphyseal growth plate, depending on the developmental stage. Pathogenesis of chondrotoxicity can probably be explained by the magnesium-chelating properties of these drugs. As juveniles are especially sensitive, use of these drugs in paediatrics should be restricted to carefully selected indications (such as the use of ciprofloxacin in cystic fibrosis). Another manifestation of the toxic effects of quinolones on connective tissue structures are tendopathies. Tendinitis and tendon ruptures have occurred as late as several months after quinolone treatment. Overall, quinolones are well tolerated drugs. Their specific toxic potentials have to be considered when they are chosen for treatment of bacterial infections.