Safety profile of grepafloxacin compared with other fluoroquinolones.

Preclinical investigations with grepafloxacin showed that its toxicological profile is similar to that of other fluoroquinolones. The photosensitizing effect of grepafloxacin was relatively weak and similar to that of ciprofloxacin. Grepafloxacin did not cause convulsions in mice when administered in conjunction with the non-steroidal anti-inflammatory drug fenbufen. Intravenous injection of grepafloxacin caused transient dysrhythmias in rabbits at a dosage of 10 mg/kg and ventricular tachycardia at 30 mg/kg iv. Joint cartilage lesions were found in juvenile dogs after iv treatment with 100 mg/kg daily. Plasma concentrations (19-24 mg/L) under these conditions were approximately ten times above a therapeutic level. Data derived from patients who had been treated with grepafloxacin in phase II and phase III multiple-dose studies (400 mg, n = 1069; 600 mg, n = 925) were available for an analysis of the patients' tolerance of the drug. The most common adverse events observed for the 400 mg and 600 mg treatments during these studies were gastrointestinal reactions, such as nausea (11% and 15%, respectively), vomiting (1% and 6%) and diarrhoea (3% and 4%). In both groups a considerable number of patients (9% and 17%) reported an unpleasant taste; this was less common in the pooled controls (1%) after treatment with drugs such as doxycycline, ciprofloxacin, amoxycillin or cefixime. Headache occurred in 4% (400 mg) and 5% (600 mg) and insomnia in 1% (400 mg) or 2% (600 mg) of the patients. Similar incidences were found for photosensitivity (1% and 2%, respectively) and for rash (1% and 2%) in the 400 mg and 600 mg groups. So far, tolerance of the new compound seems to be similar to that of other fluoroquinolones. However, incidences of nausea, vomiting and unpleasant taste were rather high during the first clinical trials, particularly after treatment with 600 mg daily. Further data are necessary for a sound evaluation of the tolerance of grepafloxacin.