PHARMACOKINETICS SECTION.

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 3H-labeled Naftifine Hydrochloride 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 half-life of approximately two to three days.

INDICATIONS & USAGE SECTION.

INDICATIONS AND USAGE. Naftifine Hydrochloride Gel USP, 1% is indicated for the topical treatment of tinea pedis, tinea cruris and tinea corporis caused by the organisms Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans1 and Epidermophyton floccosum.1 1Efficacy for this organism in this organ system was studied in fewer than 10 infections.

NURSING MOTHERS SECTION.

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 Naftifine Hydrochloride Gel, 1% is administered to nursing woman.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PACKAGE LABEL PRINCIPAL DISPLAY PANEL. Naftifine Hydrochloride Gel, USP 1% 90g Carton. Naftifine Hydrochloride Gel, USP 1% 90g Carton.

PEDIATRIC USE SECTION.

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

ADVERSE REACTIONS SECTION.

ADVERSE REACTIONS. During clinical trials with Naftifine Hydrochloride 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%).

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

Carcinogenesis, Mutagenesis, Impairment of Fertility. In 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/m2 comparison).

CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY. Naftifine hydrochloride is 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 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. Naftifine Hydrochloride 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 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 3H-labeled Naftifine Hydrochloride 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 half-life of approximately two to three days.

CONTRAINDICATIONS SECTION.

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

DESCRIPTION SECTION.

DESCRIPTION. Naftifine Hydrochloride Gel USP, 1% contains the synthetic, broad-spectrum, antifungal agent naftifine hydrochloride.Naftifine Hydrochloride Gel USP, 1% is for topical use only.Naftifine Hydrochloride Chemical StructureChemical Name (E)-N-Cinnamyl-N-methyl-1-naphthalenemethylamine hydrochloride.Naftifine hydrochloride has an empirical formula of C21H21NoHCl and molecular weight of 323.86.Contains Active IngredientNaftifine hydrochloride.... 1%Inactive IngredientsAlcohol (52%v/v), carbopol 974P, diisopropanolamine, edetate disodium, polysorbate 80 and purified water.. Naftifine Hydrochloride Chemical Structure.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION. sufficient quantity of Naftifine Hydrochloride Gel USP, 1% should be gently massaged into the affected and surrounding skin areas twice 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 Naftifine Hydrochloride Gel USP, 1% the patient should be re-evaluated.

GENERAL PRECAUTIONS SECTION.

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

HOW SUPPLIED SECTION.

HOW SUPPLIED. Naftifine Hydrochloride Gel USP, 1% is supplied in collapsible tubes in the following sizes:40g NDC 0115-1510-6360g NDC 0115-1510-5890g NDC 0115-1510-48Note: Store at 20 to 25C (68 to 77F); excursions permitted between 15 to 30C (59 to 86F) [see USP Controlled Room Temperature].To report SUSPECTED ADVERSE REACTIONS contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Manufactured by: Tolmar, Inc. Fort Collins, CO 80526Distributed by: Amneal Pharmaceuticals LLC Bridgewater, NJ 0880704006119 Rev. 11/18.

PRECAUTIONS SECTION.

PRECAUTIONS. General. Naftifine Hydrochloride Gel, 1% is for external use only. If irritation or sensitivity develops with the use of Naftifine Hydrochloride Gel, 1%, treatment should be discontinued and appropriate therapy instituted. Diagnosis of the disease should be confirmed either by direct microscopic examination of mounting of infected tissue in 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 Naftifine Hydrochloride Gel, 1% away from the eyes, nose, mouth and other mucous membranes. Avoid the use of occlusive dressings or wrappings unless otherwise directed by the physician.. Keep Naftifine Hydrochloride Gel, 1% away from the eyes, nose, mouth and other mucous membranes. Carcinogenesis, Mutagenesis, Impairment of Fertility. In 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/m2 comparison).. Pregnancy. Teratogenic EffectsReproduction 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 Naftifine Hydrochloride Gel, 1% is administered to nursing woman.. Pediatric Use. Safety and effectiveness in pediatric patients have not been established.

PREGNANCY SECTION.

Pregnancy. Teratogenic EffectsReproduction 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.

SPL UNCLASSIFIED SECTION.

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

WARNINGS SECTION.

WARNINGS. Naftifine Hydrochloride Gel, 1% is for topical use only and not for ophthalmic use.