Safety profile of the quinolones

Abstract

The most important finding from preclinical evaluation of fluoroquinolones has been their arthropathogenic potential in young animals. This toxic effect is found with all quinolones known so far and has led to the decision not to use them in children and adolescents, despite the fact that the significance of the effect for humans is still unclear. The mutagenic potential of the drugs seems to be low although bacterial DNA-metabolism is a major target of their action. Newer in-vitro methods to study topoisomerases from bacterial and mammalian cells are suitable to detect differences in the derivatives with regard to their mutagenic potential. The major adverse effects observed clinically with the four most often used fluoroquinolones norfloxacin, ciprofloxacin, ofloxacin and enoxacin are gastrointestinal disturbances (1.8-5%), reactions of the central nervous system (0.9-1.6%) and skin reactions (0.6-1.4%). Higher incidences have been noticed during the clinical evaluation of fleroxacin at doses of 400 mg or more. A comparison of the adverse reaction frequencies of fluoroquinolones with those of other antimicrobial agents can most closely be made with the results from double-blind studies. Such results show that in most cases fluoroquinolones have been tolerated as well as or better than conventional drugs. Clinically relevant drug interactions have been observed with some quinolones that are metabolized primarily in the liver: enoxacin and ciprofloxacin reduce the theophylline clearance. Also, interactions of quinolones with Mg2(+)-containing antacids, which result in tremendous loss of bioavailability, are of therapeutic importance. Overall, fluoroquinolones are well tolerated and the incidences of side effects are similar to those of other antibacterials.