MetroCream

ADVERSE REACTIONS: In controlled clinical trials, the total incidence of adverse reactions associated with the use of METROCREAM ® 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.

CONTRAINDICATIONS: METROCREAM ® (metronidazole topical cream) Topical Cream is contraindicated in individuals with a history of hypersensitivity to metronidazole, or other ingredients of the formulation.

DESCRIPTION: METROCREAM ® Topical Cream contains metronidazole, USP, at a concentration of 7.5 mg per gram (0.75%) in an emollient cream consisting of benzyl alcohol, emulsifying wax, glycerin, isopropyl palmitate, purified water, sorbitol solution, lactic acid and/or sodium hydroxide to adjust pH. Metronidazole is a member of the imidazole class of antibacterial agents and is classified therapeutically as an antiprotozoal and anti-bacterial agent. Chemically, metronidazole is 2-methyl-5-nitro-1 H- imidazole-1-ethanol. The molecular formula is C 6 H 9 N 3 O 3 and molecular weight is 171.16. Metronidazole is represented by the following structural formula:

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

INDICATIONS AND USAGE: METROCREAM ® (metronidazole topical cream) Topical Cream is indicated for topical application in the treatment of inflammatory papules and pustules of rosacea.

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

20180626

2

MetroCream metronidazole Metronidazole Metronidazole Benzyl Alcohol Glycerin Isopropyl Palmitate Water Sorbitol Lactic Acid Sodium Hydroxide Structural Formula metrocream-45g-carton

NDA020531

MetroCream

metronidazole

0299-3836

HUMAN PRESCRIPTION DRUG

TOPICAL

PACKAGE LABEL: MetroCream ® (metronidazole topical cream) TOPICAL CREAM 0.75% NET WT. 45 g NDC 0299-3836-45 Rx only GALDERMA FOR TOPICAL USE ONLY. NOT FOR OPHTHALMIC USE. STORE AT CONTROLLED ROOM TEMPERATURE, 68° TO 77°F (20°-25°C), EXCURSIONS PERMITTED BETWEEN 59° AND 86°F (15° - 30°C). Usual dosage: Apply a thin layer to entire affected areas after washing. Use morning and evening or as directed by physician. Avoid application close to the eyes. Each gram contains: Active: metronidazole 0.75% (7.5 mg). Inactive: benzyl alcohol, emulsifying wax, glycerin, isopropyl palmitate, purified water, sorbitol solution, lactic acid and/or sodium hydroxide to adjust pH. See closure for lot number and expiration date. Marketed by: GALDERMA LABORATORIES, L.P. Fort Worth, TX 76177 USA Made in Canada All trademarks are the property of their respective owners. P53315-0

HOW SUPPLIED: METROCREAM ® (metronidazole topical cream) Topical Cream, 0.75% is supplied in a 45 g aluminum tube - NDC 0299-3836-45. Storage conditions : STORE AT CONTROLLED ROOM TEMPERATURE, 68° to 77°F (20° to 25°C), EXCURSIONS PERMITTED BETWEEN 59° AND 86°F (15° - 30°C). Marketed by: GALDERMA LABORATORIES, L.P. Fort Worth, Texas 76177 USA Made in Canada All trademarks are the property of their respective owners. P53314-0 Revised: January 2017

PRECAUTIONS: General: Topical metronidazole has been reported to cause tearing of the eyes. Therefore, contact with the eyes should be avoided. If a reaction suggesting local irritation occurs, patients should be directed to use the medication less frequently or discontinue use. Metronidazole is a 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 a 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 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. Pregnancy: Teratogenic effects: Pregnancy category B: There are no adequate and well-controlled studies with the use of METROCREAM ® (metronidazole topical cream) 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 a 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, a 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.