The safety profile of
grepafloxacin has been characterized in a number of preclinical and clinical studies. Preclinical investigations have shown that its toxicologic profile is similar to that of other
fluoroquinolones, and phase I studies in humans have confirmed these data. A photosensitivity study demonstrated equivalence with
ciprofloxacin, and a study in elderly patients taking the highest clinical dose of
grepafloxacin indicated that prolongation of the QTc interval by
grepafloxacin was less than 2 ms, 15 times less than that observed in a study of
erythromycin. In phase II and III clinical investigations conducted in the United States and the United Kingdom, safety data have been gathered from more than 3000 patients with either community-acquired
pneumonia or acute bacterial exacerbations of
chronic bronchitis. The most common adverse events with
grepafloxacin 400 or 600 mg were gastrointestinal, such as
nausea,
vomiting, and
diarrhea. The frequency of these adverse events was similar to that seen with
ciprofloxacin. Significantly more patients reported a mild, unpleasant
metallic taste with
grepafloxacin than with
ciprofloxacin, but <1% of patients withdrew from
therapy because of this.
Headache was observed significantly more often in
ciprofloxacin-treated patients than in
grepafloxacin-treated patients. Recent postmarketing data confirm the good tolerability and safety profile of
grepafloxacin. These data, from a case-report study of more than 9000 patients in Germany, demonstrated that only 2.3% of patients reported adverse events when
grepafloxacin was used in routine clinical practice. The most frequently reported events were
nausea (0.8%) and gastrointestinal symptoms (0.4%).
Dizziness was reported by only 0.3% of patients, and only 4 patients (0.04%) reported
photosensitization. Adverse events did not appear to be either dose dependent or related to diagnosis. More than 400,000 patients world-wide have received
grepafloxacin treatment. No new safety issues have arisen from the spontaneous-report data and, with the exception of rare reports of an unpleasant taste, the most commonly reported events have been the same as those seen in clinical studies. These data support
grepafloxacin as a well-tolerated
fluoroquinolone suitable for the treatment of community-acquired
respiratory tract infections.