Source: European Medicines Agency (EU) Revision Year: 2020
Pharmacotherapeutic group: Chemotherapeutics for topical use
ATC Code: D06BX01
Metronidazole is a 5-nitroimidazole derivative with activity against anerobic protozoa and bacteria, due probably to an interference with DNA by a metabolite of the metronidazole.
The precise mode of action of Metronidazole in Rosacea is not known. It has been suggested that it has an anti-inflammatory effect due to an anti-oxidant activity affecting neutrophil cell function, or that it acts as a parasiticide towards Demodex folliculorum.
The gel is applied topically for its local action.
In humans, systemic absorption of 1g gel with 7.5mg Metronidazole after topical application is low (1% of oral dose). Quantifiable serum levels are in the range 25-66 ng/ml and Cmax is <5% of that observed after a 30 mg oral dose (41 ng/ml vs. 850 ng/ml); Tmax is prolonged, 5.98 hours compared to 0.97 hours orally.
Single dose studies in mouse and rat by oral, intraperitoneal and intravenous routes show a low order of toxicity. Repeat dose studies (oral and intravenous) in mouse, rat, dog, and monkey indicate a no-effect level of 75 mg/kg/day.
Reproductive studies showed no evidence of embryotoxicity or teratogenicity in mouse, rat and rabbit (oral and intravenous). Reversible male infertility was observed in rats treated with 400 mg/kg/day.
Metronidazole is mutagenic in bacteria and fungi, but is regarded as non-genotoxic in mammalian species.
No phototoxic or photogenotoxic effects were seen in studies in Chinese hamster lung cells.
Carcinogenicity studies in mouse and rats showed an increased incidence of tumours, but recent epidemiological studies in human showed no increased cancer risk.
No local dermal toxicity (irritation, sensitisation) was seen in guinea pigs.
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