Safety profile of grepafloxacin compared with other fluoroquinolones

Abstract

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.

Antimicrobial Safety and Tolerability: Differences and Dilemmas

“…In patients receiving 600 mg/day, this side effect was reported in 26% of patients [50]. Overall, figures of 17% for taste perversion and 15% for nausea were reported for grepafloxacin in preregistration trials, and abnormal liver function tests were reported in up to 16% of patients given the drug in Japan [51,52].…”

“…Although pseudomembranous colitis is certainly an unusual adverse event, it has been reported with quinolone use [23,24]. Taste perversion rates of 17% overall have been reported in patients treated with grepafloxacin [25].…”

Inhibitory effects of the quinolone antibiotics trovafloxacin, ciprofloxacin, and levofloxacin on osteoblastic cells in vitro

“…Several investigators have rcporkd quinolones to be cytotoxic to eukaryotic cells. Preclinical toxicological evaluations have revealed nephrotoxicity and cardiotoxicity in laboratory animals to which fluoroquinolones were administered (23,26). Perhapb the most notable example of quinolone-associated cytotoxicity is chondrotoxicity-the ability of the class as a whole to induce arthropathy in juvenile animals ol' many species (1).…”

Ultrastructural characterization of murine limb buds after in vitro exposure to grepafloxacin and other fluoroquinolones

“…Also, in animal experiments it exhibited a comparatively pronounced potential to induce dysrhythmia and ventricular tachycardia (Stahlmann and Schwabe 1997). Several studies have shown that grepa¯oxacin inhibits human ether-a-go-go-related gene (HERG) channels, which could explain its cardiotoxicity (Anderson et al 2001;Kang et al 2001).…”