Metronidazole - Metronidazole cream prescribing information
INDICATIONS AND USAGE
METRONIDAZOLE CREAM is indicated for the topical treatment of inflammatory lesions and erythema of rosacea.
DOSAGE AND ADMINISTRATION
Areas to be treated should be cleansed before application of METRONIDAZOLE CREAM . Apply and rub in a thin film of METRONIDAZOLE CREAM once daily to entire affected area(s). Patients may use cosmetics after application of METRONIDAZOLE CREAM .
CONTRAINDICATIONS
METRONIDAZOLE CREAM is contraindicated in those patients with a history of hypersensitivity to metronidazole or to any other ingredient in this formulation.
ADVERSE REACTIONS
Safety data from 302 patients who used METRONIDAZOLE CREAM (n=200) or vehicle control (n=102) once daily in clinical trials and experienced an adverse event considered to be treatment related include: application site reaction ( METRONIDAZOLE CREAM 1, vehicle 1), condition aggravated ( METRONIDAZOLE CREAM 1, vehicle 0), paresthesia ( METRONIDAZOLE CREAM 0, vehicle 1), acne ( METRONIDAZOLE CREAM 1, vehicle 0), dry skin ( METRONIDAZOLE CREAM 0, vehicle 2). The majority of adverse reactions were mild to moderate in severity.
Two patients treated with METRONIDAZOLE CREAM once daily discontinued treatment because of adverse events: one for a severe flare of comedonal acne and one for rosacea aggravated.
Additional clinical adverse effects reported spontaneously since the drug was marketed are uncommon and include tingling or numbness of extremities, allergic reactions, skin and eye irritation, rash, headache, nausea and dry mouth.
To report SUSPECTED ADVERSE REACTIONS, contact Oceanside Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
Drug Interactions:
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 CREAM is prescribed for patients who are receiving anticoagulant treatment, although they are less likely to occur with topical metronidazole administration because of low absorption. (See CLINICAL PHARMACOLOGY , Pharmacokinetics . )
DESCRIPTION
METRONIDAZOLE CREAM, 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 a solubility in water of 10 mg/mL at 20°C. Metronidazole is a member of the imidazole class of antibacterial agents and is classified as an antiprotozoal and antibacterial agent.
METRONIDAZOLE CREAM is an emollient cream; each gram contains 10 mg micronized metronidazole USP, in a base of glycerin USP, glyceryl monostearate NF, methylparaben NF, propylparaben NF, purified water USP, stearic acid NF and trolamine NF.
CLINICAL PHARMACOLOGY
Pharmacokinetics:
When a one gram dose of METRONIDAZOLE CREAM , 1%, was applied in a single application to the face of 16 healthy volunteers, low concentrations of metronidazole were detected in the plasma of 7 of the volunteers. The mean±SD C max of metronidazole was 27.6±7.3 ng/mL, which is about 1% of the value reported for a single 250 mg oral dose of metronidazole. The time to maximum plasma concentration (T max ) in the volunteers with detectable metronidazole was 8-12 hours after topical application.
Pharmacodynamics:
The mechanisms by which metronidazole acts in reducing inflammatory lesions of rosacea are unknown.
Clinical Studies:
Safety and efficacy of METRONIDAZOLE CREAM were evaluated in two randomized vehicle-controlled clinical studies for the treatment of rosacea, which excluded patients who had nodules, moderate or severe rhinophyma, dense telangiectases, plaque-like facial edema or ocular involvement and those who had a history of not responding to metronidazole therapy for rosacea. Of the patients included in the efficacy database (n=416), there were 142 men and 274 women. Endpoint efficacy data comparisons for patients treated with daily METRONIDAZOLE CREAM or vehicle applications are listed below.
| METRONIDAZOLE CREAM | Vehicle | |||||||
|---|---|---|---|---|---|---|---|---|
| Study 1 | Study 2 | Study 1 | Study 2 | |||||
| N | Result | N | Result | N | Result | N | Result | |
Papules + Pustules Count | ||||||||
Baseline | 89 | 15 | 92 | 19 | 50 | 18 | 49 | 17 |
Week 10 | 80 | 7• | 82 | 8 | 45 | 15 | 41 | 12 |
Reduction | 49%• | 58%• | 17% | 30% | ||||
Papules Count | ||||||||
Baseline | 89 | 13 | 92 | 17 | 50 | 15 | 49 | 15 |
Week 10 | 80 | 7• | 82 | 7 | 45 | 12 | 41 | 11 |
Reduction | 41%• | 55%• | 14% | 28% | ||||
Erythema Score | ||||||||
Baseline | 89 | 2.2 | 92 | 2.3 | 50 | 2.2 | 49 | 2.2 |
Week 10 | 80 | 1.3• | 82 | 1.4• | 45 | 1.7 | 40 | 1.8 |
Reduction | 42%• | 40%• | 25% | 19% | ||||
•Statistically significant differences between METRONIDAZOLE CREAM and vehicle groups with p≤0.05. Erythema scores: 0=none, 1=mild, 2=moderate and 3=severe.
Safety Studies:
Studies of contact sensitization (n=258), phototoxicity (n=21), and photocontact sensitization (n=29) of METRONIDAZOLE CREAM were conducted. No evidence of sensitization or phototoxicity was seen in these studies.
Clinical Studies:
Safety and efficacy of METRONIDAZOLE CREAM were evaluated in two randomized vehicle-controlled clinical studies for the treatment of rosacea, which excluded patients who had nodules, moderate or severe rhinophyma, dense telangiectases, plaque-like facial edema or ocular involvement and those who had a history of not responding to metronidazole therapy for rosacea. Of the patients included in the efficacy database (n=416), there were 142 men and 274 women. Endpoint efficacy data comparisons for patients treated with daily METRONIDAZOLE CREAM or vehicle applications are listed below.
| METRONIDAZOLE CREAM | Vehicle | |||||||
|---|---|---|---|---|---|---|---|---|
| Study 1 | Study 2 | Study 1 | Study 2 | |||||
| N | Result | N | Result | N | Result | N | Result | |
Papules + Pustules Count | ||||||||
Baseline | 89 | 15 | 92 | 19 | 50 | 18 | 49 | 17 |
Week 10 | 80 | 7• | 82 | 8 | 45 | 15 | 41 | 12 |
Reduction | 49%• | 58%• | 17% | 30% | ||||
Papules Count | ||||||||
Baseline | 89 | 13 | 92 | 17 | 50 | 15 | 49 | 15 |
Week 10 | 80 | 7• | 82 | 7 | 45 | 12 | 41 | 11 |
Reduction | 41%• | 55%• | 14% | 28% | ||||
Erythema Score | ||||||||
Baseline | 89 | 2.2 | 92 | 2.3 | 50 | 2.2 | 49 | 2.2 |
Week 10 | 80 | 1.3• | 82 | 1.4• | 45 | 1.7 | 40 | 1.8 |
Reduction | 42%• | 40%• | 25% | 19% | ||||
•Statistically significant differences between METRONIDAZOLE CREAM and vehicle groups with p≤0.05. Erythema scores: 0=none, 1=mild, 2=moderate and 3=severe.
Safety Studies:
Studies of contact sensitization (n=258), phototoxicity (n=21), and photocontact sensitization (n=29) of METRONIDAZOLE CREAM were conducted. No evidence of sensitization or phototoxicity was seen in these studies.
HOW SUPPLIED
Cream - 60 g aluminum tube - NDC 68682-202-60.
Keep out of reach of children.
Storage:
Store at controlled room temperature 20° to 25°C (68° to 77°F).
