Safety of nitroimidazoles.

The nitroimidazoles used in the treatment of anaerobic infection are well-tolerated by patients. With the possible exception of neurotoxic effects associated with high dosage, signs and symptoms of toxicity are transient and disappear soon after withdrawal of treatment. Teratogenicity tests in animals have given negative results in the case of metronidazole, ornidazole and tinidazole, and in the case of metronidazole no evidence of any adverse effect on the outcome of pregnancy was seen in women treated for trichomoniasis at various times during gestation, including the first trimester. The observed low general toxicity of nitroimidazoles is consistent with the non-occurrence of nitroreduction, as is the absence of chromosomal aberration in the circulating lymphocytes of patients receiving prolonged metronidazole therapy for Crohn's disease. Carcinogenicity tests involving the prolonged exposure of rats, mice and hamsters to a range of doses of metronidazole have given mixed results. In response to high doses, mice exhibited an increased risk of developing lung tumours, and female rats developed more liver tumours than controls. However, these effects may have been non-specific consequences of prolonged high dosage. No excesses of tumours were seen in response to lower doses and two tests in hamsters gave negative results. A follow-up of 771 women treated, 10 or more years previously, with metronidazole revealed no excess cancer risk. Thus the available information suggests that metronidazole, tinidazole and other 5-nitroimidazoles effective against anaerobic microorganisms are very safe both in the short-term and in the long-term.