Generic Name: naftifine hydrochloride
Dosage Form: gel
NAFTIN (naftifine hydrochloride) Gel, 2% is an allylamine antifungal indicated for the treatment of interdigital tinea pedis caused by the organisms Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum in patients 18 years of age and older.
Naftin Gel Dosage and Administration
Apply a thin layer of NAFTIN (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. NAFTIN (naftifine hydrochloride) Gel, 2% is not for ophthalmic, oral, or intravaginal use.
Dosage Forms and Strengths
Gel, 2%. Each gram contains 20 mg of naftifine hydrochloride in a colorless to yellow gel.
Warnings and Precautions
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 practice.
In two randomized, vehicle-controlled trials, 1143 subjects were treated with NAFTIN (naftifine hydrochloride) Gel, 2% versus 571 subjects treated with the vehicle. The trial subjects were 12 to 92 years old, were primarily male (76%), and were 59% Caucasian, 38% Black or African American, and 23% Hispanic or Latino. Subjects received doses once daily, topically, for 2 weeks to cover the affected skin areas plus a ½-inch margin of surrounding healthy skin. The most common adverse reactions were application site reactions which occurred at the rate of 2% in NAFTIN (naftifine hydrochloride) Gel, 2% arm versus 1% in vehicle arm. Most adverse reactions were mild in severity.
Cumulative irritancy testing revealed the potential for NAFTIN (naftifine hydrochloride) Gel, 2% to cause irritation. There was no evidence that NAFTIN (naftifine hydrochloride) Gel, 2% causes contact sensitization, phototoxicity, or photoallergenicity in healthy skin.
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. The following adverse reactions have been identified during postmarketing use of naftifine hydrochloride: blisters, burning sensation, crusting, dryness, erythema/redness, inflammation, irritation, maceration, pain, pruritus [mild]/itching, rash and swelling.
USE IN SPECIFIC POPULATIONS
Pregnancy Category B. There are no adequate and well-controlled trials of NAFTIN (naftifine hydrochloride) Gel, 2% in pregnant women. Because animal reproduction studies are not always predictive of human response, NAFTIN (naftifine hydrochloride) Gel, 2% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
The animal multiples of human exposure calculations were based on daily dose body surface area comparison (mg/m2) for the reproductive toxicology studies described in this section and in Section 13.1. The Maximum Recommended Human Dose (MRHD) was set at 4 g 2% gel per day (1.33 mg/kg/day for a 60 kg individual).
Systemic embryofetal development studies were conducted in rats and rabbits. Oral doses of 30, 100, and 300 mg/kg/day naftifine hydrochloride were administered during the period of organogenesis (gestational days 6 – 15) to pregnant female rats. No treatment-related effects on embryofetal toxicity or teratogenicity were noted at doses up to 300 mg/kg/day (36.5× MRHD). Subcutaneous doses of 10 and 30 mg/kg/day naftifine hydrochloride were administered during the period of organogenesis (gestational days 6 – 15) to pregnant female rats. No treatment-related effects on embryofetal toxicity or teratogenicity were noted at 30 mg/kg/day (3.7× MRHD). Subcutaneous doses of 3, 10, and 30 mg/kg/day naftifine hydrochloride were administered during the period of organogenesis (gestational days 6 – 18) to pregnant female rabbits. No treatment-related effects on embryofetal toxicity or teratogenicity were noted at 30 mg/kg/day (7.3× 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 at300 mg/kg/day (36.5× MRHD). No developmental toxicity was noted at 100 mg/kg/day (12.2× MRHD).
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 NAFTIN (naftifine hydrochloride) Gel, 2% is administered to a nursing woman.
Safety and effectiveness in pediatric patients have not been established. The number of pediatric subjects ≤ 12 years of age studied was too small to adequately assess safety and efficacy.
Naftin Gel Description
NAFTIN (naftifine hydrochloride) Gel, 2% is a clear to yellow gel for topical use only. Each gram of NAFTIN (naftifine hydrochloride) Gel, 2% contains 20 mg of naftifine hydrochloride, a synthetic allylamine antifungal compound.
Chemically, naftifine HCl is (E)-N-Cinnamyl-N-methyl-1-napthalenemethylamine hydrochloride.
The molecular formula is C21H21N∙HCl with a molecular weight of 323.86.
The structural formula of naftifine hydrochloride is:
NAFTIN (naftifine hydrochloride) Gel, 2% contains the following inactive ingredients: alcohol, benzyl alcohol, edentate disodium, hydroxyethyl cellulose, purified water, propylene glycol, polysorbate 20 and trolamine.
Naftin Gel - Clinical Pharmacology
Mechanism of Action
NAFTIN (naftifine hydrochloride) Gel, 2% is a topical antifungal drug [see Clinical Pharmacology (12.4)].
The pharmacodynamics of NAFTIN (naftifine hydrochloride) Gel, 2% have not been established.
In vitro and in vivo bioavailability studies have demonstrated that naftifine penetrates the stratum corneum in sufficient concentration to inhibit the growth of dermatophytes.
Pharmacokinetic analysis of plasma samples from 32 tinea pedis subjects treated with a mean dose of of 3.9 grams NAFTIN(naftifine hydrochloride) Gel, 2% applied once daily to both feet for 14 days showed increased exposure over the treatment period, with a geometric mean (CV%) AUC0-24 (area under plasma concentration-versus-time curve from time 0 to 24 hours) of 10.5 (118) ng∙hr/mL on Day 1 and an AUC0-24 of 70 (59) ng∙hr/mL on Day 14. The accumulation ratio based on AUC was approximately 6.
Maximum concentration (Cmax) also increased over the treatment period; geometric mean (CV%) Cmax after a single dose was 0.9 (92) ng/mL on Day 1; Cmax on Day 14 was 3.7 (64) ng/mL. Median Tmax was 20.0 hours (range: 8, 20 hours) after a single application on Day 1 and 8.0 hours (range: 0, 24 hours) on Day 14. Trough plasma concentrations increased during the trial period and reached steady state after 11 days.
In the same pharmacokinetic trial the fraction of dose excreted in urine was less than or equal to 0.01% of the applied dose.
Mechanism of Action
Naftifine is an antifungal that belongs to the allylamine class. 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. The inhibition of enzyme activity by this allylamine results in decreased amounts of sterols, especially ergosterol, and a corresponding accumulation of squalene in the cells.
Naftifine has been shown to be active against most isolates of the following fungi, both in vitro and in clinical infections, as described in the INDICATIONS AND USAGE section:
- Trichophyton rubrum
- Trichophyton mentagrophytes
- Epidermophyton floccosum
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies to evaluate the carcinogenic potential of NAFTIN (naftifine hydrochloride) Gel, 2% have not been performed.
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 (12.2× MRHD).
NAFTIN (naftifine hydrochloride) Gel, 2% has been evaluated for efficacy in two randomized, double-blind, vehicle-controlled, multicenter trials that included 1175 subjects with symptomatic and dermatophyte culture-positive tinea pedis. Subjects were randomized to receive NAFTIN (naftifine hydrochloride) Gel, 2% or vehicle. Subjects applied naftifine hydrochloride gel 2% or vehicle to the affected area of the foot once daily for 2 weeks. Signs and symptoms of tinea pedis (presence or absence of erythema, pruritus, and scaling) were assessed and potassium hydroxide (KOH) examination and dermatophyte culture were performed 6 weeks after the first treatment.
The mean age of the study population was 45 years; 77% were male; and 60% were Caucasian, 35% were Black or African American, and 26% were Hispanic or Latino. At baseline, subjects were confirmed to have signs and symptoms of tinea pedis, positive KOH exam, and confirmed dermatophyte culture. The primary efficacy endpoint was the proportion of subjects with a complete cure at 6 weeks after the start of treatment (4 weeks after the last treatment). 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 1 below. Naftin Gel demonstrated complete cure in subjects with interdigital type tinea pedis.
|Trial 1||Trial 2|
|Endpoint||Naftin Gel, 2%
|Naftin Gel, 2%
|Complete Cure*||64 (17%)||3 (2%)||104 (26%)||7 (3%)|
|Treatment Effectiveness†||207 (54%)||11 (6%)||203 (51%)||15 (7%)|
|Mycological Cure‡||250 (65%)||25 (14%)||235 (59%)||22 (10%)|
How Supplied/Storage and Handling
NAFTIN (naftifine hydrochloride) Gel, 2% is a colorless to yellow gel supplied in collapsible tubes in the following size:
45g – NDC 0259-1202-45
Store NAFTIN (naftifine hydrochloride) Gel, 2% at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].
Patient Counseling Information
- Inform patients that NAFTIN (naftifine hydrochloride) Gel, 2% is for topical use only. NAFTIN (naftifine hydrochloride) Gel, 2% is not intended for ophthalmic, oral, or intravaginal use.
- Patients should be directed to contact their physician if irritation develops with the use of NAFTIN (naftifine hydrochloride) Gel, 2% .
NAFTIN (naftifine hydrochloride) Gel, 2% is manufactured for Merz Pharmaceuticals, LLC, Greensboro, NC 27410.
NAFTIN (naftifine hydrochloride) is a registered trademark of Merz Pharmaceuticals, LLC.
PRINCIPAL DISPLAY PANEL - 45g Tube Carton
(Naftifine Hydrochloride) Gel, 2%
For Topical Use Only
Not for Ophthalmic, Oral or Intravaginal Use
naftifine hydrochloride gel
|Labeler - Merz Pharmaceuticals, LLC (126209282)|