NAFTIFINE: 121 Adverse Event Reports & Safety Profile

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

AND USAGE Naftifine hydrochloride gel USP, 2% is indicated for the treatment of interdigital tinea pedis caused by the organisms Trichophyton rubrum , Trichophyton mentagrophytes , and Epidermophyton floccosum .

Naftifine Hydrochloride

Gel USP, 2% is an allylamine antifungal indicated for the treatment of interdigital tinea pedis caused by the organisms Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum . ( 1 )

AND ADMINISTRATION Apply a thin layer of naftifine hydrochloride gel, 2% once daily to the affected areas plus an approximate ½ inch margin of healthy surrounding skin for 2 weeks. For topical use only. Naftifine hydrochloride gel, 2% is not for ophthalmic, oral, or intravaginal use. Apply a thin layer of naftifine hydrochloride gel, 2% once daily to the affected areas plus an approximate ½ inch margin of healthy surrounding skin for 2 weeks. ( 2 ) For topical use only. Naftifine hydrochloride gel, 2% is not for ophthalmic, oral, or intravaginal use. ( 2 )

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

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.

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.

PRECAUTIONS General Naftifine Hydrochloride Cream USP, 1% is for external use only. If irritation or sensitivity develops with the use of Naftifine Hydrochloride Cream USP, 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 Naftifine Hydrochloride

Cream USP, 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 mg/kg/day, 20 mg/kg/day, 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/m 2 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 Naftifine Hydrochloride Cream USP, 1% is administered to a nursing woman. Pediatric use Safety and effectiveness in pediatric patients have not been established.