OXICONAZOLE: 65 Adverse Event Reports & Safety Profile

DESCRIPTION Oxiconazole nitrate cream, 1% contains the antifungal active compound oxiconazole nitrate. This formulation is for topical dermatologic use only. Chemically, oxiconazole nitrate is 2´,4´-dichloro-2-imidazol-1-ylacetophenone ( Z )-[ 0 -(2,4-dichlorobenzyl)oxime], mononitrate. The compound has the molecular formula C 18 H 13 ON 3 CI 4

• HNO 3 , a molecular weight of 492.15, and the following structural formula: Oxiconazole nitrate is a nearly white crystalline powder, soluble in methanol; sparingly soluble in ethanol, chloroform, and acetone; and very slightly soluble in water. Oxiconazole nitrate cream contains 10 mg of oxiconazole per gram of cream in a white to off-white, opaque cream base of purified water USP, white petrolatum USP, stearyl alcohol NF, propylene glycol USP, polysorbate 60 NF, cetyl alcohol NF, and benzoic acid USP, 0.2% as a preservative. chemicalstructure

INDICATIONS AND USAGE Oxiconazole nitrate cream is indicated for the topical treatment of the following dermal infections: tinea pedis, tinea cruris, and tinea corporis due to Trichophyton rubrum , Trichophyton mentagrophytes , or Epidermophyton floccosum . Oxiconazole nitrate cream is indicated for the topical treatment of tinea (pityriasis) versicolor due to Malassezia furfur (see DOSAGE AND ADMINISTRATION and CLINICAL STUDIES ). Oxiconazole nitrate cream may be used in pediatric patients for tinea corporis, tinea cruris, tinea pedis, and tinea (pityriasis) versicolor; however, these indications for which oxiconazole nitrate cream has been shown to be effective rarely occur in children below the age of 12.

DOSAGE AND ADMINISTRATION Oxiconazole nitrate cream should be applied to affected and immediately surrounding areas once to twice daily in patients with tinea pedis, tinea corporis, or tinea cruris. Oxiconazole nitrate cream should be applied once daily in the treatment of tinea (pityriasis) versicolor. Tinea corporis, tinea cruris, and tinea (pityriasis) versicolor should be treated for 2 weeks and tinea pedis for 1 month to reduce the possibility of recurrence. If a patient shows no clinical improvement after the treatment period, the diagnosis should be reviewed. Note: Tinea (pityriasis) versicolor may give rise to hyperpigmented or hypopigmented patches on the trunk that may extend to the neck, arms, and upper thighs. Treatment of the infection may not immediately result in restoration of pigment to the affected sites. Normalization of pigment following successful therapy is variable and may take months, depending on individual skin type and incidental sun exposure. Although tinea (pityriasis) versicolor is not contagious, it may recur because the organism that causes the disease is part of the normal skin flora.

CONTRAINDICATIONS Oxiconazole nitrate cream is contraindicated in individuals who have shown hypersensitivity to any of their components.

ADVERSE REACTIONS During clinical trials, of 955 patients treated with oxiconazole nitrate cream , 1%, 41 (4.3%) reported adverse reactions thought to be related to drug therapy. These reactions included pruritus (1.6%); burning (1.4%); irritation and allergic contact dermatitis (0.4% each); folliculitis (0.3%); erythema (0.2%); and papules, fissure, maceration, rash, stinging, and nodules (0.1% each). In a controlled, multicenter clinical trial of 269 patients treated with oxiconazole nitrate lotion , 1%, 7 (2.6%) reported adverse reactions thought to be related to drug therapy. These reactions included burning and stinging (0.7% each) and pruritus, scaling, tingling, pain, and dyshidrotic eczema (0.4% each).

WARNINGS OXISTAT (oxiconazole nitrate) Lotion, 1% is for topical use only and not for oral, ophthalmic or intravaginal use.

PRECAUTIONS General Oxiconazole nitrate cream is for external dermal use only. Avoid introduction of oxiconazole nitrate cream into the eyes or vagina. If a reaction suggesting sensitivity or chemical irritation should occur with the use of oxiconazole nitrate cream, treatment should be discontinued and appropriate therapy instituted. If signs of epidermal irritation should occur, the drug should be discontinued. Information for Patients The patient should be instructed to: Use oxiconazole nitrate cream as directed by the physician. The hands should be washed after applying the medication to the affected area(s). Avoid contact with the eyes, nose, mouth, and other mucous membranes. Oxiconazole nitrate cream is for external use only. Use the medication for the full treatment time recommended by the physician, even though symptoms may have improved. Notify the physician if there is no improvement after 2 to 4 weeks, or sooner if the condition worsens (see below). Inform the physician if the area of application shows signs of increased irritation, itching, burning, blistering, swelling, or oozing. Avoid the use of occlusive dressings unless otherwise directed by the physician. Do not use this medication for any disorder other than that for which it was prescribed.

Drug Interactions

Potential drug interactions between oxiconazole nitrate cream and other drugs have not been systematically evaluated. Carcinogenesis, Mutagenesis, Impairment of Fertility Although no long-term studies in animals have been performed to evaluate carcinogenic potential, no evidence of mutagenic effect was found in 2 mutation assays (Ames test and Chinese hamster V79 in vitro cell mutation assay) or in 2 cytogenetic assays (human peripheral blood lymphocyte in vitro chromosome aberration assay and in vivo micronucleus assay in mice). Reproductive studies revealed no impairment of fertility in rats at oral doses of 3 mg/kg/day in females (1 time the human dose based on mg/m 2 ) and 15 mg/kg/day in males (4 times the human dose based on mg/m 2 ). However, at doses above this level, the following effects were observed: a reduction in the fertility parameters of males and females, a reduction in the number of sperm in vaginal smears, extended estrous cycle, and a decrease in mating frequency.

Pregnancy Teratogenic Effects Pregnancy

Category B Reproduction studies have been performed in rabbits, rats, and mice at oral doses up to 100, 150, and 200 mg/kg/day (57, 40, and 27 times the human dose based on mg/m 2 ), respectively, and revealed no evidence of harm to the fetus due to oxiconazole nitrate. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Because oxiconazole is excreted in human milk, caution should be exercised when the drug is administered to a nursing woman.

Pediatric Use

Oxiconazole nitrate cream may be used in pediatric patients for tinea corporis, tinea cruris, tinea pedis, and tinea (pityriasis) versicolor; however, these indications for which oxiconazole nitrate cream has been shown to be effective rarely occur in children below the age of 12.

Geriatric

Use A limited number of patients at or above 60 years of age (n ~ 396) have been treated with oxiconazole nitrate cream in US and non-US clinical trials, and a limited number (n = 43) have been treated with oxiconazole nitrate lotion in US clinical trials. The number of patients is too small to permit separate analysis of efficacy and safety. No adverse events were reported with oxiconazole nitrate lotion in geriatric patients, and the adverse reactions reported with oxiconazole nitrate cream in this population were similar to those reported by younger patients. Based on available data, no adjustment of dosage of oxiconazole nitrate cream in geriatric patients is warranted.

Drug Interactions: Potential drug interactions between oxiconazole nitrate and other drugs have not been systematically evaluated.

Drug

Interactions: Potential drug interactions between oxiconazole nitrate and other drugs have not been systematically evaluated.