METRONIDAZOLE

Metronidazole Gel USP, 1% contains metronidazole, USP. 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. Metronidazole is a colorless to slightly yellow gel; each gram contains 10 mg of metronidazole in a base of alcohol (10% w/w), disodium edetate, hydroxyethylcellulose, methylparaben, polyethylene glycol, propylene glycol, propylparaben, and purified water. Chemical Structure

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

Apply and rub in a thin film of metronidazole once daily to affected area(s). A gentle cleanser should be used before the application of metronidazole. Cosmetics may be applied after the application of metronidazole. Not for oral, ophthalmic or intravaginal use. Not for oral, ophthalmic or intravaginal use. Apply and rub in a thin film of metronidazole once daily to affected area(s). ( 2 ) Treated areas should be cleansed before the application of metronidazole. ( 2 ) Cosmetics may be applied after the application of metronidazole. ( 2 )

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

Most common adverse reactions (incidence > 2%) are nasopharyngitis, upper respiratory tract infection, and headache ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Taro Pharmaceuticals U.S.A., Inc. at 1-866-923-4914 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 patients used metronidazole gel USP, 1% and 189 patients 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%: Table 1: Adverse Reactions That Occurred at a Rate of ≥1% System Organ Class/Preferred Term Metronidazole Gel USP, 1% Gel Vehicle N=557 N=189 Patients with at least one AE Number (%) of Patients 186 (33.4) 51 (27.0) Infections and infestations 76 (13.6) 28 (14.8) Bronchitis 6 (1.1) 3 (1.6) Influenza 8 (1.4) 1 (0.5) Nasopharyngitis 17 (3.1) 8 (4.2) Sinusitis 8 (1.4) 3 (1.6) Upper respiratory tract infection 14 (2.5) 4 (2.1) Urinary tract infection 6 (1.1) 1 (0.5) Vaginal mycosis 1 (0.2) 2 (1.1) Musculoskeletal and connective tissue disorders 19 (3.4) 5 (2.6) Back pain 3 (0.5) 2 (1.1) Neoplasms 4 (0.7) 2 (1.1) Basal cell carcinoma 1 (0.2) 2 (1.1) Nervous system disorders 18 (3.2) 3 (1.6) Headache 12 (2.2) 1 (0.5) Respiratory, thoracic and mediastinal disorders 22 (3.9) 5 (2.6) Nasal congestion 6 (1.1) 3 (1.6) Skin and subcutaneous tissue disorders 36 (6.5) 12 (6.3) Contact dermatitis 7 (1.3) 1 (0.5) Dry skin 6 (1.1) 3 (1.6) Vascular disorders 8 (1.4) 1 (0.5) Hypertension 6 (1.1) 1 (0.5) Table 2: Local Cutaneous Signs and Symptoms of Irritation That Were Worse Than Baseline Metronidazole Gel USP, 1% Gel Vehicle Sign/Symptom N=544 N=184 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: skin irritation, 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: peripheral neuropathy. 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.

Oral metronidazole has been reported to potentiate the anticoagulant effect of coumarin and warfarin, resulting in a prolongation of prothrombin time. Drug interactions should be kept in mind when metronidazole is prescribed for patients who are receiving anticoagulant treatment, although they are less likely to occur with topical metronidazole administration because of low absorption. Oral metronidazole has been reported to potentiate the anticoagulant effect of coumarin and warfarin, resulting in a prolongation of prothrombin time. Drug interactions should be kept in mind when metronidazole is prescribed for patients who are receiving anticoagulant treatment, although they are less likely to occur with topical metronidazole administration because of low absorption. ( 7 )

Storage Conditions: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].