Safety and tolerability of intravenous-to-oral treatment and single-dose intravenous or oral prophylaxis with trovafloxacin

Background: The new fourth-generation fluoroquinolone, trovafloxacin, is active in vitro against gram-positive and gram-negative organisms, atypical pathogens, and anaerobes, and has pharmacokinetics permitting once-daily intravenous or oral dosing. Safety/tolerability data from phase II/III clinical trials of sequential intravenous alatrofloxacin to oral trovafloxacin and single-dose intravenous or oral prophylaxis are summarized. Methods: All trials were double-blind, randomized, and multicenter. In multidose trials with alatrofloxacin, 1,257 patients requiring initial intravenous therapy received once-daily alatrofloxacin (trovafloxacin prodrug, 200 or 300 mg/day) followed by oral 200 mg/day trovafloxacin. An additional 444 patients received a single alatrofloxacin or trovafloxacin dose prophylactically for surgical procedures. Results: Therapy with alatrofloxacin was well tolerated. The most common treatment-related adverse events in studies of intravenous alatrofloxacin followed by oral trovafloxacin were nausea, headache, insertion site reaction, and dizziness. In single-dose intravenous or oral prophylaxis studies, insertion-site reaction, pruritus, and insertion-site pain were the most common treatment-related adverse events. No serious quinolone toxicity or drug interactions were reported. The incidence of serious treatment-related adverse events was <1% in both the alatrofloxacin and comparator groups. In comparative trials, mortality due to all causes after trovafloxacin was similar to that after comparative agents; there was no mortality related to trovafloxacin administration. Conclusion: In this large patient sample, intravenous alatrofloxacin followed by oral trovafloxacin was safe and well tolerated. Serious adverse events, such as phototoxicity, cardiovascular toxicity, and hemolytic anemia associated with older fluoroquinolones, were not noted with trovafloxacin. No interactions of trovafloxacin with other drugs were reported. The safety and tolerability of trovafloxacin, along with in vitro activity against key pathogens and pharmacokinetics permitting once-daily administration, support its oral and intravenous use in patients with obstetric, gynecologic, and intra-abdominal infections as well as for prophylaxis of surgical infection.