Ciprofloxacin: toxicologic evaluation of additional safety data

Long-term ciprofloxacin toxicology studies, additional data on arthorpathogenic effects, embryotoxicity studies in monkeys, and further results on central nervous system/interaction toxicology are presented. In the long-term studies of rats and mice, ciprofloxacin was given as food admixture in concentrations up to 5,000 ppm for 24 and 21 months, respectively. This treatment regimen did not result in any systemic toxicity and also did not give any indication of a tumorigenic effect of ciprofloxacin. In a study of juvenile dogs to investigate development of arthropathogenic lesions using magnetic resonance imaging techniques, an increase in width of the recessus suprapatellaris occurred only in those dogs in which marginal effects developed. Thus, this technique may be a suitable method to monitor juvenile patients receiving ciprofloxacin. Ciprofloxacin was also studied for its potential to act as an abortifacient when given orally or parenterally to cynomolgus monkeys. The data obtained did not give any indication of teratogenicity or embryolethality, and mean patterns of progesterone were similar between routes of administration, dose groups, and controls. Finally, data are presented that demonstrate that central nervous system interaction toxicity between quinolones and nonsteroidal anti-inflammatory drugs can be observed in rats only at therapeutically irrelevant high dose levels.