Naftin

Naftin is part of the drug class:

• Other antifungals for topical use

You should not use naftifine topical if you are allergic to it.

It is not known whether naftifine topical will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether naftifine topical passes into breast milk or if it could affect the nursing baby. Tell your doctor if you are breast-feeding.

Naftifine topical should not be used on a child younger than 12 years old.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• severe skin irritation after applying this medicine.

Common side effects may include dryness or irritation of treated skin.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Administration

Topical Administration

Apply topically to the skin as a cream or gel.1 63

Do not apply to the eye, nose, mouth, or other mucous membranes.1 63

Do not use with occlusive dressings or wrappings, unless otherwise directed by clinician.1 63

Apply a sufficient amount of topical cream or gel; rub gently into the affected area and surrounding skin.1 22 33 39 46 47 49 50 51 53 54 60 63

Wash hands after applying.1 63

Dosage

Available as naftifine hydrochloride; dosage expressed in terms of naftifine.a

Adults

Cream: Apply once daily for 2–4 weeks.1 15 22 25 33 39 45 46 49 53 54 60

Gel: Apply twice daily (morning and evening) for 2–4 weeks.22 25 39 45 46 49 a

Clinical improvement usually occurs within the first week of treatment.22 25 39 45 If clinical improvement does not occur after 4 weeks of treatment, reevaluate diagnosis.1 63 Severe infections may require prolonged treatment.50 60 61

Cream: Apply once daily for 4–6 weeks.1 15 22 15 25 33 39 45 46 47 49 53 54 60

Gel: Apply twice daily (morning and evening) for 4–6 weeks.15 22 25 39 45 46 47 49 a

Clinical improvement usually occurs within the first week of treatment.22 25 39 45 If clinical improvement does not occur after 4 weeks of treatment, reevaluate diagnosis.1 63 Severe infections may require prolonged treatment.50 60 61

Special Populations

No special population dosage recommendations at this time.a

Storage

Topical

<30°C;1 cream is stable for 24 months after the date of manufacture.60

Room temperature.63

• Allylamine antifungal.1 3 4 5 9 11 13 14 16 21 22 23 25 29 31 35 36 37 38 41 42 43 48 63

• Usually fungicidal against susceptible dermatocytes.1 9 14 41 42 Usually fungistatic against Candida; may be fungicidal at high concentrations.1 3 9 14 41 42

• Exact mechanism unknown; 1 3 11 16 41 43 appears to interfere with sterol biosynthesis by inhibiting the enzyme squalene monooxygenase (squalene 2,3-epoxidase).1 11 13 14 16 21 41 43 The resulting accumulation of squalene (the usual substrate of the enzyme) in the cells and decreased amounts of sterols, especially ergosterol,1 3 10 11 16 41 may contribute to the antifungal effects.41

• Spectrum of antifungal activity includes many fungi, including dermatophytes and yeasts.1 2 3 4 5 8 9 12 22 23 31 37 42 Also may have in vitro activity against some gram-positive and -negative bacteria,58 60 61 and Leishmania.27

• Candida: Active in vitro against Candida albicans,1 3 4 12 36 C. krusei,4 C. parapsilosis,4 12 31 41 and C. tropicalis;12 however, less active than imidazole derivatives against Candida.36 37 56

• Dermatophytes and other fungi: Active in vitro against Aspergillus flavus,12 A. fumigatus,12 Blastomyces dermatitidis,12 Cryptococcus neoformans,12 Epidermophyton floccosum,1 4 8 12 38 42 Histoplasma capsulatum,12 Microsporum audouinii,1 M. canis,1 8 38 42 M. gypseum,1 8 Petriellidium boydii,12 Sporothrix schenckii,4 12 Trichophyton mentagrophytes,1 2 8 38 41 42 T. rubrum,1 8 38 42 T. tonsurans,1 38 T. verrucosum,42 and T. violaceum.8 38

• Also has anti-inflammatory activity when applied topically.51 52

• No reports to date of resistance in organisms originally susceptible to naftifine.60 61

Use Naftin as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Use as you have been told, even if your signs get better.
• To gain the most benefit, do not miss doses.
• Do not take this medicine by mouth. Use on your skin only. Keep out of your mouth, nose, and eyes (may burn).
• Wash your hands before and after use. Do not wash your hands after use if putting this on your hand.
• Clean affected part before use. Make sure to dry well.
• Put a thin layer on the affected skin and rub in gently.
• Do not use coverings (bandages, dressings, make-up) unless told to do so by the doctor.

What do I do if I miss a dose?

• Put on a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not put on 2 doses or extra doses.

Pregnancy

Risk Summary

There are no available data with Naftin 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 2-4% and 15-20%, 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/m2), 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, 100 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 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, 10 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, 100 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).

Lactation

Risk Summary

There is no information available on the presence of Naftin 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 Naftin 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 Naftin cream and any potential adverse effects on the breastfed infant from Naftin cream or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness of Naftin 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 Naftin 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 Naftin Cream [see Clinical Studies (14) and Clinical Pharmacology (12.3)].

Safety and effectiveness of Naftin 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 of Naftin Cream in the treatment of tinea corporis in pediatric patients less than 2 years of age have not been established.

Geriatric Use

Clinical studies of Naftin Cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Tinea Cruris

Naftin Cream has been investigated for safety and efficacy in a randomized, double-blind, vehicle-controlled, multi-center trial in 146 subjects with symptomatic and dermatophyte culture positive tinea cruris. Subjects were randomized to receive Naftin Cream or vehicle. Subjects applied Naftin Cream or vehicle to the affected area plus a ½-inch margin of healthy skin surrounding the affected area once-daily for 2 weeks. Signs and symptoms of tinea cruris (presence or absence of erythema, pruritus, and scaling) were assessed, and KOH examination and dermatophyte culture were performed at the primary efficacy endpoint at week 4.

The mean age of the trial population was 47 years and 87% were male and 43% were white. At baseline, subjects were confirmed to have signs and symptoms of tinea cruris, positive KOH exam, and confirmed dermatophyte presence based on culture results from a central mycology laboratory. The analysis of the intent-to-treat population was a comparison of the proportions of subjects with a complete cure at the week 4 visit (see Table 1). Complete cure was defined as both clinical cure (absence of erythema, pruritus, and scaling) and mycological cure (negative KOH and dermatophyte culture).

The percentage of subjects experiencing clinical cure and the percentage of subjects experiencing mycological cure at week 4 are presented individually in Table 1 below.

Interdigital Tinea Pedis

Naftin Cream has been investigated for efficacy in a randomized, double-blind, vehicle-controlled, multi-center trial in 217 subjects with symptomatic and dermatophyte culture positive interdigital tinea pedis. Subjects were randomized to receive Naftin Cream or vehicle. Subjects applied Naftin Cream or vehicle to the affected area of the foot plus a ½-inch margin of healthy skin surrounding the affected area once-daily for 2 weeks. Signs and symptoms of interdigital tinea pedis (presence or absence of erythema, pruritus, and scaling) were assessed and KOH examination and dermatophyte culture was performed at the primary efficacy endpoint at week 6.

The mean age of the trial population was 42 years and 71% were male and 57% were white. At baseline, subjects were confirmed to have signs and symptoms of interdigital tinea pedis, positive KOH exam, and confirmed dermatophyte culture. The primary efficacy endpoint was the proportions of subjects with a complete cure at the week 6 visit (see Table 2). Complete cure was defined as both a clinical cure (absence of erythema, pruritus, and scaling) and mycological cure (negative KOH and dermatophyte culture).

The efficacy results at week 6, four weeks following the end of treatment, are presented in Table 2 below. Naftin Cream demonstrated complete cure in subjects with interdigital tinea pedis, but complete cure in subjects with only moccasin type tinea pedis was not demonstrated.

Tinea Corporis

Naftin Cream has been investigated for safety and efficacy in a randomized, double-blind, vehicle-controlled, multi-center trial in 184 subjects with symptomatic and dermatophyte culture positive tinea corporis. Subjects were randomized to receive Naftin Cream or vehicle. Subjects applied the study agent to all affected body surface areas with tinea corporis plus a ½ inch margin of healthy skin surrounding the affected lesions for two weeks. Signs and symptoms of tinea corporis (presence or absence of erythema, induration, and pruritus) were assessed and KOH examination and dermatophyte culture were performed for the assessment of primary efficacy endpoint at Day 21.

The trial population was pediatric (≥2 to <18 years of age) with a median age of 9 years (Naftin Cream) or 8 years (vehicle); 61% of subjects were male and 45% were white. At baseline, subjects were confirmed to have signs and symptoms of tinea corporis, positive KOH exam, and confirmed dermatophyte culture. The primary efficacy endpoint was the proportions of subjects with a complete cure at the Day 21 visit. Complete cure was defined as both a clinical cure (absence of erythema, induration, and pruritus on all lesions present at baseline) and mycological cure (negative KOH and dermatophyte culture).

The efficacy results at Day 21, one week following the end of treatment, are presented in Table 3 below.