METRONIDAZOLE

Metronidazole Gel, 1% is a nitromidazole for topical use. Metronidazole Gel, 1% is a clear, colorless to pale yellow, aqueous gel. Each gram contains 10 mg of metronidazole. Chemically, metronidazole is 2-methyl-5-nitro-1 H- imidazole-1-ethanol. The molecular formula for metronidazole is C 6 H 9 N 3 O 3 . It has the following structural formula: Metronidazole has a molecular weight of 171.16. It is a white to pale yellow crystalline powder. It is slightly soluble in alcohol and has solubility in water of 10 mg/mL at 20˚C. Metronidazole belongs to the nitroimidazole class of compounds. The inactive ingredients are betadex, edetate disodium, hydroxyethyl cellulose, methylparaben, niacinamide, phenoxyethanol, propylene glycol, propylparaben and purified water. Structural Formula

Metronidazole Gel, 1% is indicated for the topical treatment of inflammatory lesions of rosacea. Metronidazole Gel, 1% is a nitroimidazole indicated for the topical treatment of inflammatory lesions of rosacea. ( 1 )

Cleanse treated areas before the application of Metronidazole Gel, 1%. Apply and rub in a thin film of Metronidazole Gel, 1% once daily to affected area(s). Cosmetics may be applied after the application of Metronidazole Gel, 1%. For topical use only, not for oral, ophthalmic, or intravaginal use. Cleanse treated areas before the application of Metronidazole Gel, 1% ( 2 ) Apply and rub in a thin film of Metronidazole Gel, 1% once daily to affected area(s). ( 2 ) Cosmetics may be applied after the application of Metronidazole Gel, 1%. ( 2 ) Not for oral, ophthalmic, or intravaginal use. ( 2 )

Metronidazole Gel, 1% is contraindicated in patients with a history of hypersensitivity to metronidazole or to any other ingredient in the formulation. Metronidazole Gel, 1% is contraindicated in those patients with a history of hypersensitivity to metronidazole or to any other ingredient in this formulation. ( 4 )

The following clinically significant adverse reactions are described elsewhere in the labeling: Neurologic Disease [ see Warnings and Precautions (5.1) ] Contact Dermatitis [ see Warnings and Precautions (5.3) ] Eye Irritation [ see Warnings and Precautions (5.4) ] Most common adverse reactions (incidence > 2%) are nasopharyngitis, upper respiratory tract infection, and headache. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Prasco Laboratories, at 1-866-525-0688 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In a controlled clinical trial, 557 subjects used Metronidazole Gel, 1% and 189 subjects used the gel vehicle once daily for up to 10 weeks. The following table summarizes selected adverse reactions that occurred at a rate of ≥1% and at a higher rate than vehicle: Table 1: Adverse Reactions That Occurred at a Rate of ≥1% and Higher than Vehicle in Subjects Treated with Metronidazole Gel, 1% for Up to 10 Weeks Preferred Term Metronidazole Gel, 1% Vehicle ( N= 557) N (%) ( N= 189) N (%) Influenza 8 (1.4) 1 (0.5) Upper respiratory tract infection 14 (2.5) 4 (2.1) Urinary tract infection 6 (1.1) 1 (0.5) Headache 12 (2.2) 1 (0.5) Contact dermatitis 7 (1.3) 1 (0.5) Hypertension 6 (1.1) 1 (0.5) Table 2: Local Cutaneous Signs and Symptoms of Irritation That Were Worse Than Baseline in Subjects Treated with Metronidazole Gel, 1% for Up to 10 Weeks Metronidazole Gel, 1% Vehicle Sign/Symptom ( N= 544) N (%) ( N= 184) N (%) Dryness 138 (25.4) 63 (34.2) Mild 93 (17.1) 41 (22.3) Moderate 42 (7.7) 20 (10.9) Severe 3 (0.6) 2 (1.1) Scaling 134 (24.6) 60 (32.6) Mild 88 (16.2) 32 (17.4) Moderate 43 (7.9) 27 (14.7) Severe 3 (0.6) 1 (0.5) Pruritus 86 (15.8) 35 (19.0) Mild 53 (9.7) 21 (11.4) Moderate 27 (5.0) 13 (7.1) Severe 6 (1.1) 1 (0.5) Stinging/burning 56 (10.3) 28 (15.2) Mild 39 (7.2) 18 (9.8) Moderate 7 (1.3) 9 (4.9) Severe 10 (1.8) 1 (0.5) The following additional adverse experiences have been reported with the topical use of metronidazole: transient redness, metallic taste, tingling or numbness of extremities, and nausea. 6.2 Post Marketing Experience The following adverse reaction has been identified during post-approval use of topical metronidazole. Because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure. Nervous System Disorders: Peripheral neuropathy Ophthalmic Adverse Reactions: Tearing of the eyes

Oral metronidazole has been reported to potentiate the anticoagulant effect of coumarin and warfarin, resulting in a prolongation of prothrombin time. Use caution when prescribing for patients who are receiving anticoagulant treatment. Oral metronidazole has been reported to potentiate the anticoagulant effect of coumarin and warfarin, resulting in a prolongation of prothrombin time. Use caution when administering Metronidazole Gel, 1% concomitantly to patients who are receiving anticoagulant treatment. ( 7 )