NDC 51672-1376 Naftifine Hydrochloride
Gel Topical

Product Information

Naftifine Hydrochloride is a human prescription drug product labeled by Taro Pharmaceuticals U.s.a., Inc.. The product's dosage form is gel and is administered via topical form.

Product Code51672-1376
Proprietary Name What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.
Naftifine Hydrochloride
Non-Proprietary Name What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.
Naftifine Hydrochloride
Product Type What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.
Human Prescription Drug
Dosage FormGel - A semisolid3 dosage form that contains a gelling agent to provide stiffness to a solution or a colloidal dispersion.4 A gel may contain suspended particles.
Administration Route(s) What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.
  • Topical - Administration to a particular spot on the outer surface of the body. The E2B term TRANSMAMMARY is a subset of the term TOPICAL.
Product Labeler Information What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.
Taro Pharmaceuticals U.s.a., Inc.
Labeler Code51672
FDA Application Number What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.
ANDA208201
Marketing Category What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.
ANDA - A product marketed under an approved Abbreviated New Drug Application.
Start Marketing Date What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.
04-10-2019
Listing Expiration Date What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.
12-31-2023
Exclude Flag What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".
N
NDC Code Structure

What are the uses for Naftifine Hydrochloride?


Product Characteristics

Color(s)YELLOW (C48330 - COLORLESS, TO YELLOW)

Product Packages

NDC 51672-1376-3

Package Description: 1 TUBE in 1 CARTON > 60 g in 1 TUBE

NDC 51672-1376-6

Package Description: 1 TUBE in 1 CARTON > 45 g in 1 TUBE

Product Details

What are Naftifine Hydrochloride Active Ingredients?

An active ingredient is the substance responsible for the medicinal effects of a product specified by the substance's molecular structure or if the molecular structure is not known, defined by an unambiguous definition that identifies the substance. Each active ingredient name is the preferred term of the UNII code submitted.

Naftifine Hydrochloride Active Ingredients UNII Codes

NDC to RxNorm Crosswalk

What is RxNorm? RxNorm is a normalized naming system for generic and branded drugs that assigns unique concept identifier(s) known as RxCUIs to NDC products.The NDC to RxNorm Crosswalk for this produdct indicates multiple concept unique identifiers (RXCUIs) are associated with this product:

Naftifine Hydrochloride Inactive Ingredients UNII Codes

The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

Pharmacologic Class(es)

A pharmacologic class is a group of drugs that share the same scientifically documented properties. The following is a list of the reported pharmacologic class(es) corresponding to the active ingredients of this product.

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Patient Education

Naftifine Topical

Naftifine Topical is pronounced as (naf' ti feen)

Why is naftifine topical medication prescribed?
Naftifine is used for skin infections such as athlete's foot, jock itch, and ringworm.This medication is sometimes prescribed for other uses; ask your doctor or pharmacis...
[Read More]

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Naftifine Hydrochloride Labeling and Warnings

FDA filings in the form of structured product labels are documents that include all published material associated whith this product. Product label information includes data like indications and usage generic names, contraindications, active ingredients, strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Table of Contents



1 Indications 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.


2 Dosage 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.


3 Dosage Forms And Strengths



Gel, 2%. Each gram contains 20 mg of naftifine hydrochloride in a colorless to yellow gel.


4 Contraindications



None.


5.1 Local Adverse Reactions



If irritation or sensitivity develops with the use of naftifine hydrochloride gel, treatment should be discontinued.


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.

In two randomized, vehicle-controlled trials, 1143 subjects were treated with naftifine hydrochloride gel 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 naftifine hydrochloride gel arm versus 1% in vehicle arm. Most adverse reactions were mild in severity.

In an open-label pediatric pharmacokinetics and safety trial 22 pediatric subjects 12 to 17 years of age with interdigital tinea pedis received naftifine hydrochloride gel. The incidence of adverse reactions in the pediatric population was similar to that observed in adult population.

Cumulative irritancy testing revealed the potential for naftifine hydrochloride gel to cause irritation. There was no evidence that naftifine hydrochloride gel causes contact sensitization, phototoxicity, or photoallergenicity in healthy skin.


6.2 Postmarketing Experience



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 post-approval use of naftifine hydrochloride: blisters, burning sensation, crusting, dryness, erythema/redness, inflammation, irritation, maceration, pain, pruritus [mild]/itching, rash and swelling.


Other



Risk Summary

There are no available data on naftifine hydrochloride gel use in pregnant women to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

In animal reproduction studies, no adverse effects on embryofetal development were seen at oral doses administered during the period of organogenesis up to 37 times the maximum recommended human dose (MRHD) in pregnant rats or subcutaneous doses administered during the period of organogenesis up to 4 times the MRHD in pregnant rats or 7 times the MRHD in pregnant rabbits (see Data).

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Animal Data

Systemic embryofetal development studies were conducted in rats and rabbits. For the comparison of animal to human doses, the MRHD is set at 4 g 2% gel per day (1.33 mg/kg/day for a 60 kg individual).

Oral doses of 30 mg/kg/day, 100 mg/kg/day, and 300 mg/kg/day naftifine hydrochloride were administered during the period of organogenesis to pregnant female rats. No treatment-related effects on embryofetal toxicity were noted at doses up to 300 mg/kg/day (37 times the MRHD based on mg/m2 comparison). Subcutaneous doses of 10 mg/kg/day and 30 mg/kg/day naftifine hydrochloride were administered during the period of organogenesis to pregnant female rats. No treatment-related effects on embryofetal toxicity were noted at 30 mg/kg/day (4 times the MRHD based on mg/m2 comparison). Subcutaneous doses of 3 mg/kg/day, 10 mg/kg/day, and 30 mg/kg/day naftifine hydrochloride were administered during the period of organogenesis to pregnant female rabbits. No treatment-related effects on embryofetal toxicity were noted at 30 mg/kg/day (7 times the MRHD based on mg/m2 comparison).

A peri- and post-natal development study was conducted in rats. Oral doses of 30 mg/kg/day, 100 mg/kg/day, 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 (37 times the MRHD based on mg/m2 comparison). No developmental toxicity was noted at 100 mg/kg/day (12 times the MRHD based on mg/m2 comparison).

Risk Summary

There is no information available on the presence of naftifine hydrochloride in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production after topical application of naftifine hydrochloride gel to women who are breastfeeding. It is not known whether naftifine hydrochloride is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when naftifine hydrochloride is administered to a nursing woman.

The lack of clinical data during lactation precludes a clear determination of the risk naftifine hydrochloride gel to an infant during lactation. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for naftifine hydrochloride gel and any potential adverse effects on the breastfed infant from naftifine hydrochloride gel or from the underlying maternal condition.

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
  • Manufactured by: Taro Pharmaceuticals Inc., Brampton, Ontario, Canada L6T 1C1
    Distributed by: Taro Pharmaceuticals U.S.A., Inc., Hawthorne, NY 10532
    Revised: May, 2020
    PK-9089-1 26


8.4 Pediatric Use



The safety and effectiveness of naftifine hydrochloride gel have been established in the age group 12 to 18 years of age with interdigital tinea pedis. Use of naftifine hydrochloride gel in this age group is supported by evidence from adequate and well controlled trials in adults with additional safety and PK data from an open label trial, conducted in 22 adolescents ≥12 years of age who were exposed to naftifine hydrochloride gel at a dose of approximately 4 g/day [see Clinical Pharmacology (12.3)].

Safety and effectiveness in pediatric patients <12 years of age have not been established.


8.5 Geriatric Use



During clinical trials, 99 subjects (9%) aged 65 years and over were exposed to naftifine hydrochloride gel. Safety and effectiveness were similar to those reported by younger subjects.


11 Description



Naftifine Hydrochloride Gel USP, 2% is a clear to yellow gel for topical use only. Each gram of naftifine hydrochloride gel 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:

Naftifine Hydrochloride Gel USP, 2% contains the following inactive ingredients: alcohol (95% v/v), benzyl alcohol, edetate disodium, hydroxyethyl cellulose, polysorbate 20, propylene glycol, purified water and trolamine.


12.1 Mechanism Of Action



Naftifine hydrochloride gel is a topical antifungal drug [see Clinical Pharmacology (12.4)].


12.2 Pharmacodynamics



The pharmacodynamics of naftifine hydrochloride gel have not been established.


12.3 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 naftifine hydrochloride gel 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 hours (range: 8, 20 hours) after a single application on Day 1 and 8 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 naftifine hydrochloride gel was evaluated in 22 pediatric subjects 12 to 17 years of age with tinea pedis. Subjects were treated with a mean dose of 4.1 grams naftifine hydrochloride 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 (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.


13.1 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 (36 times MRHD based on AUC 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/m2 comparison).


14 Clinical Studies



Naftifine hydrochloride 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 naftifine hydrochloride 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.

Table 1 Interdigital Tinea Pedis: Number (%) of Subjects With Complete Cure, Effective Treatment, and Mycological Cure at Week 6 Following Treatment With Naftifine Hydrochloride Gel (Full Analysis Set, Missing Values Treated as Treatment Failure)
Trial 1Trial 2
EndpointNaftifine Hydrochloride Gel, 2%
N=382
n (%)
Vehicle
N=179
n (%)
Naftifine Hydrochloride Gel, 2%
N=400
n (%)
Vehicle
N=213
n (%)
Complete Cure

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).

64 (17%)3 (2%)104 (26%)7 (3%)
Treatment Effectiveness

Effective treatment is a negative KOH preparation and negative dermatophyte culture, erythema, scaling, and pruritus grades of 0 or 1 (absent or nearly absent).

207 (54%)11 (6%)203 (51%)15 (7%)
Mycological Cure

Mycological cure is defined as negative KOH and dermatophyte culture.

250 (65%)25 (14%)235 (59%)22 (10%)

How Supplied



How Supplied

Naftifine Hydrochloride Gel USP, 2% is a colorless to yellow gel supplied in collapsible tubes in the following size:

45g – NDC 51672-1376-6

60g – NDC 51672-1376-3


Storage And Handling



Storage

Store at 20° to 25°C (68° to 77°F); [see USP Controlled Room Temperature].


17 Patient Counseling Information



  • Inform patients that naftifine hydrochloride gel is for topical use only. Naftifine hydrochloride gel is not intended for ophthalmic, oral, or intravaginal use.
  • Patients should be directed to contact their physician if irritation develops with the use of naftifine hydrochloride gel.

Principal Display Panel - 60 G Tube Carton



NDC 51672-1376-3

60 g

Naftifine Hydrochloride
Gel USP, 2%

FOR TOPICAL USE ONLY. NOT FOR OPHTHALMIC USE, ORAL OR INTRAVAGINAL USE

Rx only

Keep this and all medications out of the reach of children.

TARO


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