Naftifine Hydrochloride

1 INDICATIONS AND USAGE Naftifine Hydrochloride Cream is indicated for the treatment of interdigital tinea pedis, tinea cruris, and tinea corporis caused by the organism Trichophyton rubrum . Naftifine Hydrochloride Cream is an allylamine antifungal indicated for the treatment of interdigital tinea pedis, tinea cruris, and tinea corporis caused by the organism Trichophyton rubrum .

2 DOSAGE AND ADMINISTRATION For topical use only. Naftifine Hydrochloride Cream is not for ophthalmic, oral, or intravaginal use. Apply a thin layer of Naftifine Hydrochloride Cream once-daily to the affected areas plus a 1⁄2 inch margin of healthy surrounding skin for 2 weeks. For topical use only. Naftifine Hydrochloride Cream is not for ophthalmic, oral, or intravaginal use. ( 2 ) Apply a thin layer of Naftifine Hydrochloride Cream once-daily to the affected areas plus a 1⁄2 inch margin of healthy surrounding skin for 2 weeks. ( 2 )

3 DOSAGE FORMS AND STRENGTHS Each gram of Naftifine Hydrochloride Cream contains 20 mg of naftifine hydrochloride (2%) in a white to off-white base. Cream: 2%

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

6 ADVERSE REACTIONS The most common adverse reaction (≥1%) is pruritus. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc., at 1-866-923-4914 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. During clinical trials, 903 subjects were exposed to naftifine 1% and 2% cream formulations. A total of 564 subjects with interdigital tinea pedis, tinea cruris, or tinea corporis were treated with Naftifine Hydrochloride Cream. In two randomized, vehicle-controlled trials (400 subjects were treated with Naftifine Hydrochloride Cream). The population was 12 to 88 years old, primarily male (79%), 48% Caucasian, 36% Black or African American, 40% Hispanic or Latino and had either predominantly interdigital tinea pedis or tinea cruris. Most subjects received doses once-daily, topically, for 2 weeks to cover the affected skin areas plus a 1⁄2 inch margin of surrounding healthy skin. In the two vehicle-controlled trials, 17.5% of Naftifine Hydrochloride Cream treated subjects experienced an adverse reaction compared with 19.3% of vehicle subjects. The most common adverse reaction (≥1%) is pruritus. Most adverse reactions were mild in severity. The incidence of adverse reactions in the Naftifine Hydrochloride Cream treated population was not significantly different than in the vehicle treated population. In a third randomized, vehicle-controlled trial, 116 pediatric subjects with tinea corporis were treated with Naftifine Hydrochloride Cream. The population was aged ≥2 to <18 years (mean age of 9 years), predominately male (61%), 47% White, 51% Black or African American, 92% Hispanic or Latino, and infected with tinea corporis. Naftifine Hydrochloride Cream was topically applied once daily for 2 weeks to all affected body surface areas with tinea corporis plus a 1⁄2 inch margin of healthy skin surrounding the affected lesions. The incidence of adverse reactions in the Naftifine Hydrochloride Cream treated population was not significantly different than in the vehicle treated population. In two open-label pediatric pharmacokinetics and safety trials, 49 pediatric subjects 2 to <18 years of age with interdigital tinea pedis, tinea cruris, and tinea corporis received Naftifine Hydrochloride Cream. The incidence of adverse reactions in the pediatric population was similar to that observed in the adult population. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of naftifine hydrochloride: redness/irritation, inflammation, maceration, swelling, burning, blisters, serous drainage, crusting, headache, dizziness, leukopenia, agranulocytosis. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no available data with Naftifine Hydrochloride Cream in pregnant women to inform the drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, no adverse effects on embryofetal development were seen at oral doses administered during the period of organogenesis up to 18 times the maximum recommended human dose (MRHD) in pregnant rats or subcutaneous doses administered during the period of organogenesis up to 2 times the MRHD in pregnant rats or 4 times the MRHD in pregnant rabbits [see Data ] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Systemic embryofetal development studies were conducted in rats and rabbits. For the comparison of animal to human doses based on body surface area comparison (mg/m 2 ), the MRHD is set at 8 g 2% cream per day (2.67 mg/kg/day for a 60 kg individual). Oral doses of 30 mg/kg/day, 100 mg/kg/day and 300 mg/kg/day naftifine hydrochloride were administered during the period of organogenesis to pregnant female rats. No treatment-related effects on embryofetal development were noted at doses up to 300 mg/kg/day (18 times MRHD). Subcutaneous doses of 10 mg/kg/day and 30 mg/kg/day naftifine hydrochloride were administered during the period of organogenesis to pregnant female rats. No treatment-related effects on embryofetal development were noted at 30 mg/kg/day (2 times MRHD). Subcutaneous doses of 3 mg/kg/day, 10 mg/kg/day and 30 mg/kg/day naftifine hydrochloride were administered during the period of organogenesis to pregnant female rabbits. No treatment-related effects on embryofetal development were noted at 30 mg/kg/day (4 times MRHD). A peri- and post-natal development study was conducted in rats. Oral doses of 30 mg/kg/day, 100 mg/kg/day and 300 mg/kg/day naftifine hydrochloride were administered to female rats from gestational day 14 to lactation day 21. Reduced body weight gain of females during gestation and of the offspring during lactation was noted at 300 mg/kg/day (18 times MRHD). No developmental toxicity was noted at 100 mg/kg/day (6 times MRHD). 8.2 Lactation Risk Summary There is no information available on the presence of Naftifine Hydrochloride Cream in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. The lack of clinical data during lactation precludes a clear determination of the risk of Naftifine Hydrochloride Cream to an infant during lactation; therefore, the development and health benefits of breastfeeding should be considered along with the mother's clinical need for Naftifine Hydrochloride Cream and any potential adverse effects on the breastfed infant from Naftifine Hydrochloride Cream or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of Naftifine Hydrochloride Cream have been established in pediatric patients age 12 and above with interdigital tinea pedis and tinea cruris and age 2 and above with tinea corporis [see Clinical Studies (14) and Clinical Pharmacology (12.3) ] . Use of Naftifine Hydrochloride Cream in these age groups is supported by evidence from adequate and well controlled studies in adults and children, with additional safety and PK data from two open label trials conducted in 49 pediatric subjects exposed to Naftifine Hydrochloride Cream [see Clinical Studies (14) and Clinical Pharmacology (12.3) ] . Safety and effectiveness of Naftifine Hydrochloride Cream in the treatment of tinea cruris and interdigital tinea pedis in pediatric patients less than 12 years of age have not been established. Safety and effectiveness …

12.1 Mechanism of Action Naftifine Hydrochloride Cream is a topical antifungal drug [see Clinical Pharmacology (12.4) ]

11 DESCRIPTION Naftifine Hydrochloride Cream is a white to off-white cream for topical use only. Each gram of Naftifine Hydrochloride Cream contains 20 mg of naftifine hydrochloride (2%), a synthetic allylamine antifungal compound. Chemically, naftifine HCl is (E)-N-Cinnamyl-N-methyl-1-napthalenemethylamine hydrochloride. The molecular formula is C 21 H 21 N∙HCl with a molecular weight of 323.86. The structural formula of naftifine hydrochloride is: Naftifine Hydrochloride Cream contains the following inactive ingredients: benzyl alcohol, cetyl alcohol, cetyl esters wax, hydrochloric acid, isopropyl myristate, polysorbate 60, purified water, sodium hydroxide, sorbitan monostearate, and stearyl alcohol. Chemical Structure

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Naftifine Hydrochloride Cream USP, 2% is a white to off-white cream supplied in tubes in the following sizes: 30 g – NDC 51672-1368-2 45 g – NDC 51672-1368-6 60 g – NDC 51672-1368-3 Storage: Store Naftifine Hydrochloride Cream USP, 2% at 20° to 25°C (68 ° to 77°F) [see USP Controlled Room Temperature].