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 ½ 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 ½ inch margin of healthy surrounding skin for 2 weeks. ( 2 )

5 WARNINGS AND PRECAUTIONS Discontinue treatment if redness or irritation develops with Naftifine Hydrochloride Cream use. ( 5.1 ) 5.1 Local Adverse Reactions Discontinue treatment if irritation or sensitivity develops with the use of Naftifine Hydrochloride Cream. Direct patients to contact their physician if these conditions develop following use of Naftifine Hydrochloride Cream.

4 CONTRAINDICATIONS None None

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).

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 ½ 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 ½ 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.