DESCRIPTION
MetroLotion® (metronidazole lotion) Topical Lotion contains metronidazole, USP, at a concentration of 7.5 mg per gram (0.75% w/w) in a lotion consisting of benzyl alcohol, carbomer 941, cyclomethicone, glycerin, glyceryl stearate, light mineral oil, PEG-100 stearate, polyethylene glycol 400, potassium sorbate, purified water, steareth-21, stearyl alcohol, and sodium hydroxide and/or lactic acid to adjust pH.
Metronidazole is an imidazole and is classified therapeutically as an antiprotozoal and antibacterial agent. Chemically, metronidazole is 2-methyl-5-nitro-1H-imidazole-1-ethanol. The molecular formula is C6H9N3O3 and molecular weight is 171.16. Metronidazole is represented by the following structural formula:
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CLINICAL PHARMACOLOGY
The mechanisms by which metronidazole acts in the treatment of rosacea are unknown, but appear to include an anti-inflammatory effect.
Pharmacokinetics:
Absorption of metronidazole after topical application of MetroLotion® Topical Lotion is lass complete and more prolonged than after oral administration. Detectable plasma levels were found in all subjects following the administration of a 1 gram dose of MetroLotion® Topical Lotion (containing 7.5 mg of metronidazole) applied every morning and evening for 4 days to the faces of 8 patients. The highest concentration (96 ng/mL) seen following the morning dose on Day 5 was approximately 80 times lower than the peak concentrations produced by a single 250 mg tablet of metronidazole. The mean (± SD) AUC0-24 after twice daily administration was 962 ± 373 ng.hr/mL.
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CLINICAL STUDIES
A controlled clinical study was conducted in 144 patients with moderate to severe rosacea, in which MetroLotion® Topical Lotion was compared with its vehicle. Applications were made twice daily for 12 weeks during which patients were instructed to avoid spicy foods, thermally hot foods and drinks, alcoholic beverages, and caffeine. Patients were also provided samples of a soapless cleansing lotion and, if requested, a moisturizer. MetroLotion® Topical Lotion was significantly more effective than its vehicle in mean percent reduction of inflammatory lesions associated with rosacea and in the investigators’ global assessment of improvement. The results of the mean percent reduction in inflammatory lesion counts from baseline after 12 weeks of treatment and the investigators’ global assessment of improvement at week 12 are presented in the following table:
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Efficacy Outcomes at Week 12
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Mean Percent Reduction in Inflammatory Lesion Counts from Baseline
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MetroLotion® Topical Lotion
N=65 |
Vehicle Lotion
N=60 |
| 55% |
20% |
Investigators' Global Assessment of Improvement
(percent change from baseline)
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| |
|
Worse |
No
Change |
Minimal
Improvement |
Definite
Improvement |
Marked
Improvement |
Clear |
MetroLotion®
Topical Lotion
N=65 |
5% |
12% |
11% |
32% |
32% |
8% |
Vehicle Lotion
N=60 |
15% |
27% |
23% |
15% |
20% |
0% |
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| The scale is based on the following definitions: |
| Worse: |
Exacerbation of either erythema or quantitative
assessment of papules and/or pustules. |
| No Change: |
Condition remains the same. |
| Minimal Improvement: |
Slight improvement in the quantitative assessment
of papules and/or pustules, and/or slight improvement
in erythema. |
| Definite Improvement: |
More pronounced improvement in the quantitative
assessment of papules and/or pustules, and/or
more pronounced improvement in erythema. |
| Marked Improvement: |
Obvious improvement in the quantitative assessment
of papules and/or pustules, and/or obvious
improvement in erythema. |
| Clear |
No papules or pustules and minimal residual or no
erythema. |
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