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Metronidazole Cream, 1%
FOR TOPICAL USE ONLY
(NOT FOR OPHTHALMIC USE)
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 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 a solubility in water of 10 mg/mL at 20°C. Metronidazole is a member of the imidazole class of anti-bacterial agents and is classified as an antiprotozoal and anti-bacterial agent.
Metronidazole Cream, 1%, is an emollient cream; each gram contains 10 mg micronized metronidazole USP, in a base of purified water USP, stearic acid NF, glyceryl monostearate NF, glycerin USP, methylparaben NF, trolamine NF and propylparaben NF.
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CLINICAL PHARMACOLOGY
Pharmacokinetics
When 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 Cmax 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 (Tmax) 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, 1%, 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, 1%, or vehicle applications are listed below.
Inflammatory Lesion Counts and Erythema Severity Scores in Two Clinical Trials for Rosacea | Metronidazole Cream, 1% | Vehicle |
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| Study 1 | Study 2 | Study 1 | Study 2 |
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| N | Result | N | Result | N | Result | N | Result |
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| 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% |
Safety Studies
Studies of contact sensitization (n=258), phototoxicity (n=21), and photocontact sensitization (n=29) of Metronidazole Cream, 1%, were conducted. No evidence of sensitization or phototoxicity was seen in these studies.
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