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Naftin Gel

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Naftin Gel

CLINICAL PHARMACOLOGY

Mechanism Of Action

NAFTIN Gel is a topical antifungal drug.

Pharmacodynamics

The pharmacodynamics of NAFTIN Gel have not been established.

Pharmacokinetics

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 subjects with tinea pedis treated with a mean dose of 3.9 grams NAFTIN Gel applied once daily to both feet for 14 days showed increased exposure over the treatment period, with a geometric mean (CV%) AUC 0-24 (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 AUC 0-24 of 70 (59) ng•hr/mL on Day 14. The accumulation ratio based on AUC was approximately 6. Maximum concentration (C max ) also increased over the treatment period; geometric mean (CV%) C max after a single dose was 0.9 (92) ng/mL on Day 1; C max on Day 14 was 3.7 (64) ng/mL. Median T max 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 during the treatment period was less than or equal to 0.01% of the applied dose.

In a second trial, the pharmacokinetics of NAFTIN Gel was evaluated in 22 pediatric subjects 12-17 years of age with tinea pedis. Subjects were treated with a mean dose of 4.1 grams NAFTIN Gel applied to the affected area once daily for 14 days. The results showed that the systemic exposure increased over the treatment period. Geometric mean (CV%) AUC0-24 was 15.9 (212) ng•hr/mL on Day 1 and 60.0 (131) ng•hr/mL on Day 14. Geometric mean (CV%) Cmax after a single dose was 1.40 (154) ng/mL on Day 1 and 3.81 (154) ng/mL on Day 14. The fraction of dose excreted in urine during the treatment period was less than or equal to 0.003% of the applied dose.

Microbiology

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.

Mechanism of Resistance

To date, a mechanism of resistance to naftifine has not been identified.

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

Clinical Studies

NAFTIN Gel has been evaluated for efficacy in two randomized, double-blind, vehicle-controlled, multicenter trials that included 1175 subjects with symptomatic and dermatophyte culture-positive interdigital tinea pedis. Subjects were randomized to receive NAFTIN Gel 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 interdigital 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 interdigital 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.

Table 1 : Interdigital Tinea Pedis: Number (%) of Subjects with Complete Cure, Effective Treatment, and Mycological Cure at Week 6 Following Treatment with NAFTIN Gel (Full Analysis Set, Missing Values Treated as Treatment Failure)

Endpoint Trial 1 Trial 2
NAFTIN Gel, 2%
N=382
n (%)
Vehicle
N=179
n (%)
NAFTIN Gel, 2%
N=400
n (%)
Vehicle
N=213
n (%)
Complete Curea 64 (17%) 3 (2%) 104 (26%) 7 (3%)
Treatment Effectivenessb 207 (54%) 11 (6%) 203 (51%) 15 (7%)
Mycological Curec 250 (65%) 25 (14%) 235 (59%) 22 (10%)
a Complete cure is a composite endpoint of both mycological cure and clinical cure. Clinical cure is defined as the absence of erythema, pruritus, and scaling (grade of 0).
b Effective treatment is a negative KOH preparation and negative dermatophyte culture, erythema, scaling, and pruritus grades of 0 or 1 (absent or nearly absent).
c Mycological cure is defined as negative KOH and dermatophyte culture.

Last reviewed on RxList: 10/27/2014
This monograph has been modified to include the generic and brand name in many instances.

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