Metronidazole Gel

Name: Metronidazole Gel

What is the dosage for topical metronidazole?

To treat rosacea, a thin film of metronidazole gel should be rubbed on affected areas once or twice daily.

The usual dose of vaginal metronidazole gel is one applicator full (containing 37.5mg of metronidazole) intravaginally twice daily for five days. It should be applied once in the morning and once in the evening.

Indications

Rosadan® (metronidazole) Gel is indicated for topical application in the treatment of inflammatory papules and pustules of rosacea.

Clinical pharmacology

Bioavailability studies on the topical administration of 1 gram of Rosadan® (metronidazole) Gel (7.5 mg of metronidazole) to the face of 10 rosacea patients showed a maximum serum concentration of 66 nanograms per milliliter in one patient. This concentration is approximately 100 times less than concentrations afforded by a single 250 mg oral tablet. The serum metronidazole concentrations were below the detectable limits of the assay at the majority of time points in all patients. Three of the patients had no detectable serum concentrations of metronidazole at any time point. The mean dose of gel applied during clinical studies was 600 mg which represents 4.5 mg of metronidazole per application. Therefore, under normal usage levels, the formulation affords minimal serum concentrations of metronidazole. The mechanisms by which Rosadan® (metronidazole) Gel acts in the treatment of rosacea are unknown, but appear to include an anti-inflammatory effect.

Side effects

The following adverse experiences have been reported with the topical use of metronidazole: burning, skin irritation, dryness, transient redness, metallic taste, tingling or numbness of extremities and nausea.

Read the entire FDA prescribing information for Rosadan Gel (Metronidazole Gel)

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Dosage Forms and Strengths

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

Metronidazole Gel Description

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 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. 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.

Nonclinical Toxicology

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.

In several long-term studies in mice, oral doses of approximately 225 mg/m2/day or greater (approximately 37 times the human topical dose on a mg/m2 basis) 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/m2/day (144 times the human dose).

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 one published study, using albino hairless mice, intraperitoneal administration of metronidazole at a dose of 45 mg/m2/day (approximately 7 times the human topical dose on a mg/m2 basis) was associated with an increase in ultraviolet radiation induced skin carcinogenesis. Neither dermal carcinogenicity nor photocarcinogenicity studies have been performed with Metronidazole Gel USP, 1% or any marketed metronidazole formulations.

Clinical Studies

In a randomized, vehicle-controlled trial, 746 subjects with rosacea were treated with Metronidazole Gel USP, 1% or gel vehicle once daily for 10 weeks. Most subjects had "moderate" rosacea at baseline. Efficacy was determined by recording reduction in inflammatory lesion counts and success rate in the Investigator Global Assessment (percentage of subjects "clear" and "almost clear" of rosacea at the end of the study). The scale is based on the following definitions:

Table 3: Investigator Global Assessment Scale
Score Grade Definition
0 Clear No signs or symptoms present; at most, mild erythema
1 Almost Clear Very mild erythema present. Very few small papules/pustules
2 Mild Mild erythema. Several small papules/pustules
3 Moderate Moderate erythema. Several small or large papules/pustules, and up to 2 nodules
4 Severe Severe erythema. Numerous small and/or large papules/pustules, up to several nodules

The results are shown in the following table:

Table 4: Inflammatory Lesion Counts and Global Scores in a Clinical Trial of Rosacea
Metronidazole Gel USP, 1% 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 Metronidazole Gel USP, 1% 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.

The contribution to efficacy of individual components of the vehicle has not been established.

Patient Counseling Information

Patients using Metronidazole Gel USP, 1% should receive the following information and instructions:

  1. This medication is to be used as directed.
  2. It is for external use only.
  3. Avoid contact with the eyes.
  4. Cleanse affected area(s) before applying Metronidazole Gel USP, 1%.
  5. This medication should not be used for any condition other than that for which it is prescribed.
  6. Keep out of reach of children.
  7. Patients should report any adverse reaction to their physicians.

Rx Only

Mfd. by: Taro Pharmaceutical Industries Ltd.
Haifa Bay, Israel 2624761
Dist. by: Taro Pharmaceuticals U.S.A., Inc.
Hawthorne, NY 10532

Revised: September 2017
20419-0917-1
782

PRINCIPAL DISPLAY PANEL - 45 g Tube Carton

NDC 51672-4164-6

45 g

Metronidazole
Gel USP, 1%

FOR TOPICAL USE ONLY. NOT FOR ORAL, OPHTHALMIC OR INTRAVAGINAL USE.

Rx only

Keep this and all medications out of the reach of children.

TARO

METRONIDAZOLE 
Metronidazole Gel
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:51672-4164
Route of Administration TOPICAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Metronidazole (Metronidazole) Metronidazole 10 mg  in 1 g
Inactive Ingredients
Ingredient Name Strength
alcohol  
edetate disodium  
methylparaben  
polyethylene glycol, unspecified  
propylparaben  
propylene glycol  
water  
Product Characteristics
Color YELLOW (clear to yellow) Score     
Shape Size
Flavor Imprint Code
Contains     
Packaging
# Item Code Package Description
1 NDC:51672-4164-6 1 TUBE in 1 CARTON
1 45 g in 1 TUBE
2 NDC:51672-4164-3 1 TUBE in 1 CARTON
2 60 g in 1 TUBE
3 NDC:51672-4164-9 1 BOTTLE, PUMP in 1 CARTON
3 55 g in 1 BOTTLE, PUMP
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA204651 03/14/2017
Labeler - Taro Pharmaceuticals U.S.A., Inc. (145186370)
Establishment
Name Address ID/FEI Operations
Taro Pharmaceutical Industries Ltd. 600072078 MANUFACTURE(51672-4164)
Revised: 09/2017   Taro Pharmaceuticals U.S.A., Inc.
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