Naftin

ADVERSE REACTIONS During clinical trials with Naftin ® Gel, 1%. the incidence of adverse reactions was as follows: burning/stinging (5.0%), itching (1.0%), erythema (0.5%), rash (0.5%), skin tenderness (0.5%).

CONTRAINDICATIONS Naftin ® Gel, 1% is contraindicated in individuals who have shown hypersensitivity to any of its components.

DESCRIPTION Naftin ® Gel, 1% contains the synthetic, broad-spectrum, antifungal agent naftifine hydrochloride. Naftin ® Gel, 1% is for topical use only. CHEMICAL NAME (E)-N-Cinnamyl-N-methyl-1-naphthalenemethylamine hydrochloride. Naftifine hydrochloride has an empirical formula of C 21 H 21 N•HCl and a molecular weight of 323.86. Chemical Structure Contains Active Ingredient Naftifine hydrochloride 1%. Inactive Ingredients Naftin ® Gel, 1% contains polysorbate 80, carbomer 934P, diisopropanolamine, edetate disodium, alcohol (52%v/v), and purified water.

DOSAGE AND ADMINISTRATION A sufficient quantity of Naftin ® Gel, 1% should be gently massaged into the affected and surrounding skin areas twice a day, in the morning and evening. The hands should be washed after application. If no clinical improvement is seen after four weeks of treatment with Naftin ® Gel, 1%, the patient should be re-evaluated.

INDICATIONS AND USAGE Naftin ® Gel, 1% is indicated for the topical treatment of tinea pedis, tinea cruris, and tinea corporis caused by the organisms Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans * Efficacy for this organism in this organ system was studied in fewer than 10 infections. , Epidermophyton floccosum * .

WARNINGS Naftin ® Gel, 1% is for topical use only and not for ophthalmic use.

CLINICAL PHARMACOLOGY Naftifine Hydrochloride is a synthetic allylamine derivative. The following in vitro data are available but their clinical significance is unknown. Naftifine hydrochloride has been shown to exhibit fungicidal activity in vitro against a broad spectrum of organisms, including Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Epidermophyton floccosum, Microsporum canis, Microsporum audouini, and Microsporum gypseum, and fungistatic activity against Candida species, including Candida albicans. Naftin ® Gel, 1% has only been shown to be clinically effective against the disease entities listed in the INDICATIONS AND USAGE section. Although the exact mechanism of action against fungi is not known, naftifine hydrochloride appears to interfere with sterol biosynthesis by inhibiting the enzyme squalene 2, 3-epoxidase. This inhibition of enzyme activity results in decreased amounts of sterols, especially ergosterol, and a corresponding accumulation of squalene in the cells. Pharmacokinetics In vitro and in vivo bioavailability studies have demonstrated that naftifine penetrates the stratum corneum in sufficient concentration to inhibit the growth of dermatophytes. Following single topical applications of 3 H- labeled naftifine gel 1% to the skin of healthy subjects, up to 4.2% of the applied dose was absorbed. Naftifine and/or its metabolites are excreted via the urine and feces with a half-life of approximately two to three days.

Pharmacokinetics In vitro and in vivo bioavailability studies have demonstrated that naftifine penetrates the stratum corneum in sufficient concentration to inhibit the growth of dermatophytes. Following single topical applications of 3 H- labeled naftifine gel 1% to the skin of healthy subjects, up to 4.2% of the applied dose was absorbed. Naftifine and/or its metabolites are excreted via the urine and feces with a half-life of approximately two to three days.

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Naftin NAFTIFINE HYDROCHLORIDE ALCOHOL WATER EDETATE DISODIUM CARBOMER HOMOPOLYMER TYPE B (ALLYL SUCROSE CROSSLINKED) POLYSORBATE 80 DIISOPROPANOLAMINE NAFTIFINE HYDROCHLORIDE NAFTIFINE

Carcinogenesis, mutagenesis, impairment of fertility In a 2-year dermal carcinogenicity study, naftifine hydrochloride cream was administered to Sprague-Dawley rats at topical doses of 1%, 2% and 3% (10, 20, and 30 mg/kg/day naftifine hydrochloride). No drug-related tumors were noted in this study up to the highest dose evaluated in this study of 30 mg/kg/day [3.6 times the maximum recommended human dose (MRHD) based on mg/m2 comparison]. Naftifine hydrochloride revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitro genotoxicity tests (Ames assay and Chinese hamster ovary cell chromosome aberration assay) and one in vivo genotoxicity test (mouse bone marrow micronucleus assay). Oral administration of naftifine hydrochloride to rats, throughout mating, gestation, parturition and lactation, demonstrated no effects on growth, fertility or reproduction, at doses up to 100 mg/kg/day (12 times MRHD based on mg/m 2 comparison).

NDA019356

Naftin

NAFTIFINE HYDROCHLORIDE

54766-770

HUMAN PRESCRIPTION DRUG

TOPICAL

PRINCIPAL DISPLAY PANEL - 40g Tube Carton NDC 54766-770-40 NAFTIN ® 40g gel NAFTIFINE HCl 1% GEL Rx Only 40g Carton

Rx ONLY

Information for patients The patient should be told to: Avoid the use of occlusive dressings or wrappings unless otherwise directed by the physician. Keep Naftin ® Gel, 1% away from the eyes, nose, mouth and other mucous membranes.

Nursing mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Naftin ® Gel,1 % is administered to a nursing woman.

Pediatric use Safety and effectiveness in pediatric patients have not been established.

Pregnancy Teratogenic Effects Reproduction studies have been performed in rats and rabbits (via oral administration) at doses 150 times or more than the topical human dose and have revealed no evidence of impaired fertility or harm to the fetus due to naftifine. 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.

Teratogenic Effects Reproduction studies have been performed in rats and rabbits (via oral administration) at doses 150 times or more than the topical human dose and have revealed no evidence of impaired fertility or harm to the fetus due to naftifine. 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.

HOW SUPPLIED Naftin ® (naftifine hydrochloride) Gel, 1% is supplied in collapsible tubes in the following sizes 40g – NDC 54766-770-40 60g – NDC 54766-770-60 90g – NDC 54766-770-90 Note: Store Naftin ® Gel, 1% at room temperature.

Note: Store Naftin ® Gel, 1% at room temperature.

General Naftin ® Gel, 1%, is for external use only. If irritation or sensitivity develops with the use of Naftin ® Gel, 1%, treatment should be discontinued and appropriate therapy instituted. Diagnosis of the disease should be confirmed either by direct microscopic examination of a mounting of infected tissue in a solution of potassium hydroxide or by culture on an appropriate medium.

PRECAUTIONS General Naftin ® Gel, 1%, is for external use only. If irritation or sensitivity develops with the use of Naftin ® Gel, 1%, treatment should be discontinued and appropriate therapy instituted. Diagnosis of the disease should be confirmed either by direct microscopic examination of a mounting of infected tissue in a solution of potassium hydroxide or by culture on an appropriate medium. Information for patients The patient should be told to: Avoid the use of occlusive dressings or wrappings unless otherwise directed by the physician. Keep Naftin ® Gel, 1% away from the eyes, nose, mouth and other mucous membranes. Carcinogenesis, mutagenesis, impairment of fertility In a 2-year dermal carcinogenicity study, naftifine hydrochloride cream was administered to Sprague-Dawley rats at topical doses of 1%, 2% and 3% (10, 20, and 30 mg/kg/day naftifine hydrochloride). No drug-related tumors were noted in this study up to the highest dose evaluated in this study of 30 mg/kg/day [3.6 times the maximum recommended human dose (MRHD) based on mg/m2 comparison]. Naftifine hydrochloride revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitro genotoxicity tests (Ames assay and Chinese hamster ovary cell chromosome aberration assay) and one in vivo genotoxicity test (mouse bone marrow micronucleus assay). Oral administration of naftifine hydrochloride to rats, throughout mating, gestation, parturition and lactation, demonstrated no effects on growth, fertility or reproduction, at doses up to 100 mg/kg/day (12 times MRHD based on mg/m 2 comparison). Pregnancy Teratogenic Effects Reproduction studies have been performed in rats and rabbits (via oral administration) at doses 150 times or more than the topical human dose and have revealed no evidence of impaired fertility or harm to the fetus due to naftifine. 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 It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Naftin ® Gel,1 % is administered to a nursing woman. Pediatric use Safety and effectiveness in pediatric patients have not been established.