Does ciprofloxacin interact with cyclosporine?

OBJECTIVE: To provide the reader with a review of the literature that evaluates whether a pharmacokinetic or pharmacodynamic drug interaction exists between ciprofloxacin and cyclosporine. DATA SOURCES: A MEDLINE search was used to identify pertinent review articles, pharmacokinetic studies, and case reports. STUDY SELECTION: As both pharmacokinetic trials and case reports were few in number, all available sources were reviewed. DATA EXTRACTION: A few case reports were reviewed; however, data were extracted primarily from prospective human studies involving cyclosporine pharmacokinetic profiles. DATA SYNTHESIS: Ciprofloxacin has been reported to interact with cyclosporine during concomitant use through an interaction with the cytochrome P-450 system or by additive nephrotoxicity. Because ciprofloxacin may be used to treat a variety of infections in transplant recipients who receive cyclosporine, it is important to determine whether an interaction exists. Although cyclosporine is known to cause nephrotoxicity, only a few reports of ciprofloxacin-induced acute renal failure exist, all involving an immune-mediated interstitial nephritis. Four case reports have suggested a possible pharmacokinetic or pharmacodynamic drug interaction between cyclosporine and ciprofloxacin; however, many pharmacokinetic studies have refuted these reports. Several studies performing cyclosporine pharmacokinetic profiles have documented no increased cyclosporine concentrations, thus supporting the premise that ciprofloxacin does not interact with cyclosporine. CONCLUSIONS: Controlled studies involving cyclosporine pharmacokinetic profiles do not support a pharmacokinetic or pharmacodynamic drug interaction between ciprofloxacin and cyclosporine. Although anecdotal case reports have suggested synergistic nephrotoxicity, no clear correlation can be made. Based on our review of the literature, it can be concluded that cyclosporine and ciprofloxacin may be used together safely at the recommended dosages without increased cyclosporine monitoring.