Adverse reactions in a dose-ranging study with a new long-acting fluoroquinolone, fleroxacin

New fluoroquinolones have generally been well tolerated. In a double-blind evaluation of oral fleroxacin, using 400, 600, or 800 mg once daily for 7 days in an ambulatory setting for treatment of uncomplicated genital infections, we encountered unexpectedly high rates of adverse reactions. The objective of this analysis was to determine whether any factors in addition to dose could be found to account for our observations. Adverse reactions developed in 66 (84%) of 79 individuals, and severe reactions arose in 38 (48%). Most frequent were central nervous system reactions (70%), with insomnia being especially frequent (49%); gastrointestinal reactions (39%) and photosensitivity reactions (10%) were also common. Development of any reaction (central nervous system reactions, insomnia, and severe intestinal reactions) was dose related. Development of photosensitivity reactions correlated with an outdoor occupation. No other factors, including usual daily caffeine use, correlated with the development of adverse reactions. In our study, fleroxacin taken as a single daily 600- or 800-mg dose was associated with an unacceptably high rate of adverse reactions. Other studies are required to determine whether this problem is unique to fleroxacin or will occur with higher doses of other fluoroquinolones possessing similar chemical modifications and/or good tissue penetration and very long half-lives.