METRONIDAZOLE TOPICAL GEL USP 0.75%

FOR TOPICAL USE ONLY
NOT FOR OPHTHALMIC USE
Rx only

Metronidazole Topical Gel USP 0.75% contains metronidazole, USP, at a concentration of 7.5 mg per gram (0.75%) in a gel consisting of purified water, methylparaben, propylparaben, propylene glycol, carbomer 940, sodium hydroxide, and edetate disodium. Metronidazole is classified therapeutically as an antiprotozoal and anti-bacterial agent. Chemically, metronidazole is named 2-methyl-5-nitroimidazole-1-ethanol and has the following structure:

Bioavailability studies on the topical administration of 1 gram of metronidazole topical gel (7.5 mg of metronidazole) to the face of 10 rosacea patients showed a maximum serum concentration of 66 nanograms per milliliter in one patient. This concentration is approximately 100 times less than concentrations afforded by a single 250 mg oral tablet. The serum metronidazole concentrations were below the detectable limits of the assay at the majority of time points in all patients. Three of the patients had no detectable serum concentrations of metronidazole at any time point. The mean dose of gel applied during clinical studies was 600 mg which represents 4.5 mg of metronidazole per application. Therefore, under normal usage levels, the formulation affords minimal serum concentrations of metronidazole. The mechanisms by which metronidazole topical gel acts in the treatment of rosacea are unknown, but appear to include an anti-inflammatory effect.

Metronidazole topical gel is indicated for topical application in the treatment of inflammatory papules and pustules of rosacea.

Metronidazole topical gel is contraindicated in individuals with a history of hypersensitivity to metronidazole, parabens, or other ingredients of the formulation.

Metronidazole has shown evidence of carcinogenic activity in a number of studies involving chronic, oral administration in mice and rats but not in studies involving hamsters.

Metronidazole has shown evidence of mutagenic activity in several in vitro bacterial assay systems. In addition, a dose-response increase in the frequency of micronuclei was observed in mice after intraperitoneal injections and an increase in chromosome aberrations have been reported in patients with Crohn's disease who were treated with 200-1200 mg/day of metronidazole for 1 to 24 months. However, no excess chromosomal aberrations in circulating human lymphocytes have been observed in patients treated for 8 months.

There has been no experience to date with the use of metronidazole topical gel in pregnant patients. Metronidazole crosses the placental barrier and enters the fetal circulation rapidly. No fetotoxicity was observed after oral metronidazole in rats or mice. However, because animal reproduction studies are not always predictive of human response and since oral metronidazole has been shown to be a carcinogen in some rodents, this drug should be used during pregnancy only if clearly needed.

The following adverse experiences have been reported with the topical use of metronidazole: burning, skin irritation, dryness, transient redness, metallic taste, tingling or numbness of extremities and nausea.

Apply and rub in a thin film of metronidazole topical gel twice daily, morning and evening, to entire affected areas after washing. Areas to be treated should be cleansed before application of metronidazole topical gel. Patients may use cosmetics after application of metronidazole topical gel.

Metronidazole Topical Gel USP 0.75% is supplied as follows:

45 gram tube NDC 0168-0275-45

Store at 20°-25°C (68°-77°F)
[see USP Controlled Room Temperature].

E. FOUGERA & CO.
a division of Altana Inc.
MELVILLE, NEW YORK 11747

I2275
R1/06
#87