DailyMed Label: METROGEL

DailyMed Label: METROGEL

2023

DailyMed Prescription

METROGEL

metronidazole

Galderma Laboratories, L.P.

NDC: 0299-3820

NDC: 0299-3820

NDC: 0299-3820

METROGEL (metronidazole) topical gel, 1% is a nitroimidazole for topical use. METROGEL is a clear, colorless to pale yellow, aqueous gel. Each gram contains 10 mg of metronidazole. Chemically, metronidazole is 2-methyl-5-nitro-1 Himidazole- 1-ethanol. The molecular formula for metronidazole is C6H9N3O3. 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

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

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

Gel, 1%.  METROGEL is a clear, colorless to pale yellow gel.  Each gram of METROGEL contains 10 mg (1%) of metronidazole. Gel, 1%

METROGEL is contraindicated in patients with a history of hypersensitivity to metronidazole or to any other ingredient in the formulation. METROGEL is contraindicated in those patients with a history of hypersensitivity to metronidazole or to any other ingredient in this formulation. ( 4 )

Neurologic Disease : Peripheral neuropathy, characterized by numbness or paresthesia of an extremity has been reported in patients treated with systemic metronidazole. Peripheral neuropathy has been reported with the post approval use of topical metronidazole. Immediate reevaluate METROGEL therapy if abnormal neurologic signs appear. (5.1) Blood Dyscrasias : METROGEL is a nitroimidazole; use with care in patients with evidence of, or history of, blood dyscrasia. (5.2) Contact Dermatitis : If dermatitis occurs, patients may need to discontinue use. ( 5.3 )  Eye Irritation : Topical metronidazole has been reported to cause tearing of the eyes. Avoid contact with the eyes. ( 5.4 ) Peripheral neuropathy, characterized by numbness or paresthesia of an extremity, has been reported in patients treated with systemic metronidazole. Peripheral neuropathy has been reported with the post approval use of topical metronidazole. Immediately reevaluate METROGEL therapy if abnormal neurologic signs appear. Administer metronidazole with caution to patients with central nervous system diseases. METROGEL is a nitroimidazole; use with care in patients with evidence of, or history of, blood dyscrasia. Irritant and allergic contact dermatitis have been reported with METROGEL. If dermatitis occurs, patients may need to discontinue use. Topical metronidazole has been reported to cause tearing of the eyes.  Avoid contact with the eyes.

The following clinically significant adverse reactions are described elsewhere in the labeling:

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 METROGEL concomitantly to patients who are receiving anticoagulant treatment. ( 7 )

Lactation: Breastfeeding not recommended. (8.2 ) Risk Summary Available data have not established an association between metronidazole use during pregnancy and major birth defects, miscarriage or other adverse maternal or fetal outcomes. No fetotoxicity was observed after oral administration of metronidazole in pregnant rats or mice. The available data do not allow the calculation of relevant comparisons between the systemic exposures of metronidazole observed in animal studies to the systemic exposures that would be expected in humans after topical use of METROGEL. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Risk Summary It is not known whether metronidazole is present in human milk after topical administration. Published literature reports the presence of metronidazole in human milk after oral administration. There are no data on the effects of metronidazole on milk production. Because of the potential for serious adverse reactions, advise patients that breastfeeding is not recommended during treatment with METROGEL. Safety and effectiveness of METROGEL have not been established in pediatric patients. Sixty-six subjects aged 65 years and older were treated with METROGEL in the clinical study. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

How Supplied METROGEL®is clear, colorless to pale yellow in color, and supplied as follows: 60 gram tube – NDC 0299-3820-60 Storage and Handling Store at controlled room temperature: 20° to 25°C (68° to 77°F), excursions permitted between 15° and 30°C (59° and 86°F).

The mechanism of action of metronidazole in the treatment of rosacea is unknown. The pharmacodynamics of metronidazole in association with the treatment of rosacea are unknown. Cardiac Electrophysiology: The effect of METROGEL on the QTc interval has not been adequately characterized. Topical administration of a one-gram dose of METROGEL to the face of 13 subjects with moderate to severe rosacea once daily for 7 days resulted in a mean + SD C max of metronidazole of 32 + 9 ng/mL. The mean + SD AUC (0-24) was 595 + 154 ng*hr/mL. The mean C max and AUC (0-24) are less than 1% of the value reported for a single 250 mg oral dose of metronidazole. The time to maximum plasma concentration (T max ) was 6-10 hours after topical application.

Metronidazole has shown evidence of carcinogenic activity in studies involving chronic oral administration in mice and rats, but not in studies involving hamsters. In several long-term studies in mice, oral doses of approximately 225 mg/m 2 /day or greater were associated with an increase in pulmonary tumors and lymphomas. Several long-term oral studies in the rat have shown statistically significant increases in mammary and hepatic tumors at doses >885 mg/m 2 /day. Metronidazole has shown evidence of mutagenic activity in several in vitro bacterial assay systems. In addition, a dose-related increase in the frequency of micronuclei was observed in mice after intraperitoneal injections. An increase in chromosomal aberrations in peripheral blood lymphocytes was reported in patients with Crohn’s disease who were treated with 200 to 1200 mg/day of metronidazole for 1 to 24 months. However, in another study, no increase in chromosomal aberrations in circulating lymphocytes was observed in patients with Crohn’s disease treated with the drug for 8 months.

In a randomized, vehicle-controlled trial, 746 subjects with rosacea were treated with METROGEL or vehicle once daily for 10 weeks. Most subjects had a disease severity score of 3 (“moderate”) on the 5-point Investigator Global Assessment (IGA) scale, with 8 to 50 inflammatory lesions and no more than two nodules at baseline. The co-primary efficacy endpoints were the percent reduction in inflammatory lesion counts and percentage of subjects with success on IGA, defined as an IGA score of 0 (“clear”) or 1 ( “almost clear”) at Week 10. The efficacy results are shown in the following table: Table 3: Inflammatory Lesion Counts and Global Scores in Subjects with Rosacea at Week 10 in a Clinical Trial   METROGEL Vehicle N Results N (%) N Results N (%) Inflammatory lesions 557   189   Baseline, mean count   18.3   18.4 Week-10, mean count   8.9   12.8 Reduction   9.4 (50.7)   5.6 (32.6) Investigator Global Assessment 557   189   Subject clear or almost clear   214 (38.42)   52 (27.51) Subject with no change   159 (28.5)   77 (40.7) Subjects treated with METROGEL experienced a mean reduction of 9.4 inflammatory lesions in the Week-10 LOCF group, compared to a reduction of 5.6 for those treated with vehicle, or a difference in means of 3.8 lesions.

metrogel 1% (metronidazole) Gel 1% For topical use only NDC  0299-3820-60 Rx Only NET WT. 60 g For topical use only. Not for oral, ophthalmic or intravaginal use. Store at controlled room temperature, 68° to 77°F (20° - 25°C), excursions permitted between 59° to 86°F (15° - 30°C). Keep out of reach of children. Usual dosage:  Apply a thin film once a day to the affected areas.  See package insert for complete prescribing instructions. Each gram contains: 10 mg (1%) metronidazole as active ingredient in a gel base consisting of betadex, edetate disodium, hydroxyethl cellulose, methylparaben, niacinamide, phenoxyethanol, propylene glycol, propylparben, and purified water. Marketed by: GALDERMA LABORATORIES, L.P. Fort Worth, TX 76177 USA All trademarks are the property of their respective owners. Made in Canada. P50741-6