Metronidazole

INDICATIONS AND USAGE Metronidazole topical lotion is indicated for topical application in the treatment of inflammatory papules and pustules of rosacea. CLINICAL STUDIES A controlled clinical study was conducted in 144 patients with moderate to severe rosacea, in which metronidazole 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. Metronidazole topical lotion was significantly more effective than its vehicle in mean percent reduction of inflammatory lesions associated with rosacea and in the investigator's 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: Efficacy Outcomes at Week 12 Mean Percent Reduction in Inflammatory Lesion Counts from Baseline Metronidazole Topical Lotion N=65 Vehicle Lotion N=60 55% 20% Investigators' Global Assessment of Improvement (percent change from baseline) Worse No Change Minimal Improvement Definite Improvement Marked Improvement Clear Metronidazole Topical Lotion N=65 5% 12% 11% 32% 32% 8% Vehicle Lotion N=60 15% 27% 23% 15% 20% 0% 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.

DOSAGE AND ADMINISTRATION Apply a thin layer to entire affected areas after washing. Use morning and evening or as directed by physician. Avoid application close to the eyes. Patients may use cosmetics after waiting for the metronidazole topical lotion to dry (not less than 5 minutes).

CONTRAINDICATIONS Metronidazole topical lotion is contraindicated in individuals with a history of hypersensitivity to metronidazole or to other ingredients of the formulation.

Drug Interactions Oral metronidazole has been reported to potentiate the anticoagulant effect of warfarin and coumarin anticoagulants, resulting in a prolongation of prothrombin time. The effect of topical metronidazole on prothrombin time is not known.

Pregnancy: Teratogenic Effects: Pregnancy Category B There are no adequate and well-controlled studies with the use of metronidazole topical lotion in pregnant women. Metronidazole crosses the placental barrier and enters the fetal circulation rapidly. No fetotoxicity was observed after oral administration of metronidazole in rats or mice. However, because animal reproduction studies are not always predictive of human response and since oral metronidazole has been shown to be a carcinogen in some rodents, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers After oral administration, metronidazole is secreted in breast milk in concentrations similar to those found in the plasma. Even though blood levels are significantly lower with topically applied metronidazole than those achieved after oral administration of metronidazole, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

ADVERSE REACTIONS In a controlled clinical trial, safety data from 141 patients who used metronidazole topical lotion (n=71), or the lotion vehicle (n=70), twice daily and experienced a local cutaneous adverse event which may or may not have been related to the treatments include: local allergic reaction, metronidazole topical lotion 2 (3%), lotion vehicle 0; contact dermatitis, metronidazole topical lotion 2 (3%), lotion vehicle 1 (1%); pruritus, metronidazole topical lotion 1 (1%), lotion vehicle 0; skin discomfort (burning and stinging), metronidazole topical lotion 1 (1%), lotion vehicle 2 (3%); erythema, metronidazole topical lotion 4 (6%), lotion vehicle 0; dry skin, metronidazole topical lotion 0, lotion vehicle 1 (1%); and worsening of rosacea, metronidazole topical lotion 1 (1%), and lotion vehicle 7 (10%). The following additional adverse experiences have been reported with the topical use of metronidazole: skin irritation, transient redness, metallic taste, tingling or numbness of extremities, and nausea.