INDICATIONS & USAGE SECTION.

INDICATIONS AND USAGE. Metronidazole Topical Cream is indicated for topical application in the treatment of inflammatory papules and pustules of rosacea.

INFORMATION FOR PATIENTS SECTION.

Information for patients: This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes.

NURSING MOTHERS SECTION.

Nursing mothers: After oral administration, metronidazole is secreted in breast milk in concentrations similar to those found in the plasma. Even though blood levels are significantly lower with topically applied metronidazole than those achieved after oral administration of metronidazole, decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PACKAGE LABEL PRINCIPAL DISPLAY PANEL 45 GRAM TUBENDC 0168-0323-46Fougera(R)METRONIDAZOLETOPICAL CREAM 0.75% Rx only FOR TOPICAL USE ONLYNOT FOR OPHTHALMIC USEStore at 20C to 25C (68F to 77F), excursions permitted 15C to 30C(59F to 86F). [See USP Controlled Room Temperature].KEEP OUT OF THE REACH OF CHILDREN.NET WT 45 grams 45gramTubeLabel.

PEDIATRIC USE SECTION.

Pediatric use: Safety and effectiveness in pediatric patients have not been established.

ADVERSE REACTIONS SECTION.

ADVERSE REACTIONS. In controlled clinical trials, the total incidence of adverse reactions associated with the use of metronidazole topical cream was approximately 10%. Skin discomfort (burning and stinging) was the most frequently reported event followed by erythema, skin irritation, pruritus and worsening of rosacea. All individual events occurred in less than 3% of patients.The following additional adverse experiences have been reported with the topical use of metronidazole: dryness, transient redness, metallic taste, tingling or numbness of extremities and nausea.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

Carcinogenesis, mutagenesis, impairment of fertility: Metronidazole has shown evidence of carcinogenic activity in 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, 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 Crohns disease who were treated with 200-1200 mg/day of metronidazole for to 24 months. However, no excess chromosomal aberrations in circulating human lymphocytes have been observed in patients treated for months.

CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY. The mechanisms by which metronidazole acts in the treatment of rosacea are unknown, but appear to include an anti-inflammatory effect.

CONTRAINDICATIONS SECTION.

CONTRAINDICATIONS. Metronidazole topical cream is contraindicated in individuals with history of hypersensitivity to metronidazole, or other ingredients of the formulation.

DESCRIPTION SECTION.

DESCRIPTION. Metronidazole Topical Cream contains metronidazole, USP, at concentration of 7.5 mg per gram (0.75%) in an emollient cream consisting of emulsifying wax, sorbitol solution, glycerin, isopropyl palmitate, benzyl alcohol, lactic acid, and/or sodium hydroxide to adjust pH, and purified water. Metronidazole is member of the imidazole class of anti-bacterial agents and is classified therapeutically as an antiprotozoal and antibacterial agent. Chemically, metronidazole is 2-Methyl-5-nitroimidazole-1-ethanol. The molecular formula is C6H9N3O3 and molecular weight is 171.16. Metronidazole is represented by the following structural formula:. structure.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION. Apply and rub in thin layer of metronidazole topical cream twice daily, morning and evening, to entire affected areas after washing.Areas to be treated should be washed with mild cleanser before application. Patients may use cosmetics after application of metronidazole topical cream.

DRUG INTERACTIONS SECTION.

Drug interactions: Oral metronidazole has been reported to potentiate the anticoagulant effect of warfarin and coumarin anticoagulants, resulting in prolongation of prothrombin time. The effect of topical metronidazole on prothrombin time is not known.

GENERAL PRECAUTIONS SECTION.

General: Topical metronidazole has been reported to cause tearing of the eyes. Therefore, contact with the eyes should be avoided. If reaction suggesting local irritation occurs, patients should be directed to use the medication less frequently or discontinue use. Metronidazole is nitroimidazole and should be used with care in patients with evidence of, or history of blood dyscrasia.

HOW SUPPLIED SECTION.

HOW SUPPLIED. Metronidazole Topical Cream 0.75% is supplied in 45 gram tube,NDC 0168-0323-46. Storage conditions: Store at 20C to 25C (68F to 77F), excursions permitted 15C to 30C(59F to 86F). [See USP Controlled Room Temperature].E. FOUGERA CO.A division of Fougera Pharmaceuticals Inc.MELVILLE, NEW YORK 11747 46273863AR07/202029.

PRECAUTIONS SECTION.

PRECAUTIONS. General: Topical metronidazole has been reported to cause tearing of the eyes. Therefore, contact with the eyes should be avoided. If reaction suggesting local irritation occurs, patients should be directed to use the medication less frequently or discontinue use. Metronidazole is nitroimidazole and should be used with care in patients with evidence of, or history of blood dyscrasia.. Information for patients: This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes.. Drug interactions: Oral metronidazole has been reported to potentiate the anticoagulant effect of warfarin and coumarin anticoagulants, resulting in prolongation of prothrombin time. The effect of topical metronidazole on prothrombin time is not known.. Carcinogenesis, mutagenesis, impairment of fertility: Metronidazole has shown evidence of carcinogenic activity in 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, 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 Crohns disease who were treated with 200-1200 mg/day of metronidazole for to 24 months. However, no excess chromosomal aberrations in circulating human lymphocytes have been observed in patients treated for months.. Pregnancy: Teratogenic effects: Pregnancy category BThere are no adequate and well-controlled studies with the use of metronidazole topical cream in pregnant women. 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 carcinogen in some rodents, this drug should be used during pregnancy only if clearly needed.. Nursing mothers: After oral administration, metronidazole is secreted in breast milk in concentrations similar to those found in the plasma. Even though blood levels are significantly lower with topically applied metronidazole than those achieved after oral administration of metronidazole, decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.. Pediatric use: Safety and effectiveness in pediatric patients have not been established.

PREGNANCY SECTION.

Pregnancy: Teratogenic effects: Pregnancy category BThere are no adequate and well-controlled studies with the use of metronidazole topical cream in pregnant women. 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 carcinogen in some rodents, this drug should be used during pregnancy only if clearly needed.

SPL UNCLASSIFIED SECTION.

FOR TOPICAL USE ONLYNOT FOR OPHTHALMIC USERx only.

STORAGE AND HANDLING SECTION.

Storage conditions: Store at 20C to 25C (68F to 77F), excursions permitted 15C to 30C(59F to 86F). [See USP Controlled Room Temperature].E. FOUGERA CO.A division of Fougera Pharmaceuticals Inc.MELVILLE, NEW YORK 11747 46273863AR07/202029.