Mechanism Of Action
NAFTIN Gel is a topical
The pharmacodynamics of NAFTIN
Gel 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 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
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.
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
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:
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)
|NAFTIN Gel, 2%
|NAFTIN Gel, 2%
|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