Mentax® Cream, 1%, contains the synthetic antifungal agent, butenafine hydrochloride. Butenafine is a member of the class of antifungal compounds known as benzylamines which are structurally related to the allylamines.

Butenafine HCl is designated chemically as N-4-tert-butylbenzyl-N-methyl-1- naphthalenemethylamine hydrochloride. The compound has the empirical formula C₂₃H₂₇N•HCl, a molecular weight of 353.93, and the following structural formula:

Butenafine HCl is a white, odorless, crystalline powder. It is freely soluble in methanol, ethanol, and chloroform, and slightly soluble in water. Each gram of Mentax® Cream, 1%, contains 10 mg of butenafine HCl in a white cream base of purified water USP, propylene glycol dicaprylate, glycerin USP, cetyl alcohol NF, glyceryl monostearate SE, white petrolatum USP, stearic acid NF, polyoxyethylene (23) cetyl ether, benzyl alcohol NF, diethanolamine NF, and sodium benzoate NF.

Last updated on RxList: 4/3/2009

Mentax® (butenafine HCl cream), 1%, is indicated for the topical treatment of the following dermatologic infections: tinea (pityriasis) versicolor due to M. furfur (formerly P. orbiculare), interdigital tinea pedis (athlete's foot), tinea corporis (ringworm) and tinea cruris (jock itch) due to E. floccosum, T. mentagrophytes, T. rubrum, and T. tonsurans. Butenafine HCl cream was not studied in immunocompromised patients. (See DOSAGE AND ADMINISTRATION Section).

Patients with tinea (pityriasis) versicolor should apply Mentax® once daily for two weeks. In the treatment of interdigital tinea pedis, Mentax® should be applied twice daily for 7 days OR once daily for 4 weeks (NOTE: in separate clinical trials, the 7-day dosing regimen was less efficacious than the 4-week regimen (see Clinical Studies Section). While the clinical significance of this difference is unknown, these data should be carefully considered before selecting the dosage regiment for patients at risk for the development of bacterial cellulitis of the lower extremity associated with interdigital cracking/fissuring).

Patients with tinea corporis or tinea cruris should apply Mentax® once daily for two weeks.

Sufficient Mentax® Cream should be applied to cover affected areas and immediately surrounding skin of patients with tinea versicolor, interdigital tinea pedis, tinea corporis, and tinea cruris. If a patient shows no clinical improvement after the treatment period, the diagnosis and therapy should be reviewed.

Mentax® (butenafine HCl cream) Cream, 1%, is supplied in tubes in the following sizes:

15-gram tube (NDC 62794-151-02)
30-gram tube (NDC 62794-151-03)

STORE BETWEEN 5°C and 30°C (41° and 86°F).

Manufactured by: DPT Laboratories San Antonio, TX 78215. Distributed by: Bertek Pharmaceuticals Inc. Morgantown, WV 26505. June 6, 2001.

Last updated on RxList: 4/3/2009

In controlled clinical trials, 9 (approximately 1%) of 815 patients treated with Mentax® Cream, 1%, reported adverse events related to the skin. These included burning/stinging, itching, and worsening of the condition. No patient treated with Mentax® Cream, 1%, discontinued treatment due to an adverse event. In the vehicle-treated patients, two of 718 patients discontinued because of treatment-site adverse events, one of which was severe burning/stinging and itching at the site of application.

In uncontrolled clinical trials, the most frequently reported adverse events in patients treated with Mentax® Cream, 1%, were: contact dermatitis, erythema, irritation, and itching, each occurring in less than 2% of patients.

In provocative testing in over 200 subjects, there was no evidence of allergic contact sensitization for either the cream or the vehicle base for Mentax® Cream, 1%.

Potential drug interactions between Mentax® (butenafine HCl cream) Cream, 1%, and other drugs have not been systematically evaluated.

Last updated on RxList: 4/3/2009

Mentax® (butenafine HCl cream) Cream, 1%, is not for ophthalmic, oral, or intravaginal use.

General

Mentax® Cream, 1%, is for external use only. If irritation or sensitivity develops with the use of Mentax® Cream, 1%, treatment should be discontinued and appropriate therapy instituted. Diagnosis of the disease should be confirmed either by culture on an appropriate medium, [except M. furfur (formerly P. orbiculare)] or by direct microscopic examination of infected superficial epidermal tissue in a solution of potassium hydroxide.

Patients who are known to be sensitive to allylamine antifungals should use Mentax® (butenafine HCl cream) Cream, 1%, with caution, since cross-reactivity may occur.

Use Mentax® Cream, 1%, as directed by the physician, and avoid contact with the eyes, nose, and mouth, and other mucous membranes.

Carcinogenesis, Mutagenesis, Impairment of Fertlity

Long-term studies to evaluate the carcinogenic potential of Mentax® Cream 1% have not been conducted. Two in vitro assays (bacterial reverse mutation test and chromosome aberration test in Chinese hamster lymphocytes) and one in vivo study (rat micronucleus bioassay) revealed no mutagenic or clastogenic potential for butenafine.

In subcutaneous reproductive studies in rats at 25 mg/kg/day (6 times the maximum possible systemic dose) in humans based on a mg/m² comparison) dose level, butenafine did not produce any adverse effects on male or female fertility.

Pregnancy

Teratogenic effects: Pregnancy Category B

Subcutaneous or topical doses of butenafine (25 to 50 mg/kg/day) (equivalent to 5 to 20 times the maximum possible systemic dose in humans based on a mg/m² comparison) were not teratogenic in rats and rabbits. In an oral teratogenicity study in rabbits (80, 200, and 400 mg butenafine HCl/kg/day) (equivalent to 3 to 16 times the maximum possible systemic dose in humans based on a mg/m² comparison), no treatment-related external, visceral, or skeletal malformations or variations were observed. There are, however, no adequate and well-controlled studies that have been conducted with topically applied butenafine in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known if butenafine HCl is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised in prescribing Mentax® Cream, 1%, to a nursing woman. Nursing mothers should avoid application of Mentax® Cream, 1%, to the breast.

Pediatric Use

Safety and efficacy in pediatric patients below the age of 12 years have not been studied. Use of Mentax® Cream, 1%, in pediatric patients 12 to 16 years of age is supported by evidence from adequate and well-controlled studies of Mentax® Cream, 1%, in adults.

Last updated on RxList: 4/3/2009

Overdosage of butenafine HCl in humans has not been reported to date.

Mentax® (butenafine HCl cream) Cream, 1%, is contraindicated in individuals who have known or suspected sensitivity to Mentax® Cream, 1%, or any of its components.

Last updated on RxList: 4/3/2009

Pharmacokinetics

In one study conducted in healthy subjects for 14 days, 6 grams of Mentax® Cream, 1%, was applied once daily to the dorsal skin (3,000 cm²) of 7 subjects, and 20 grams of the cream was applied once daily to the arms, trunk and groin areas (10,000 cm²) of another 12 subjects. After 14 days of topical applications, the 6-gram dose group yielded a mean peak plasma butenafine HCl concentration, Cmax, of 1.4 ± 0.8 ng/mL, occurring at a mean time to the peak plasma concentration, Tmax, of 15 ± 8 hours, and a mean area under the plasma concentration-time curve, AUC_{0-24 hrs} of 23.9 ± 11.3 ng-hr/mL. For the 20-gram dose group, the mean Cmax was 5.0 ± 2.0 ng/mL, occurring at a mean Tmax of 6 ± 6 hours, and the mean AUC_{0-24 hrs} was 87.8 ± 45.3 ng-hr/mL. A biphasic decline of plasma butenafine HCl concentrations was observed with the half-lives estimated to be 35 hours and > 150 hours, respectively.

At 72 hours after the last dose application, the mean plasma concentrations decreased to 0.3 ± 0.2 ng/mL for the 6-gram dose group and 1.1 ± 0.9 ng/mL for the 20-gram dose group. Low levels of butenafine HCl remained in the plasma 7 days after the last dose application (mean: 0.1 ± 0.2 ng/mL for the 6-gram dose group, and 0.7 ± 0.5 ng/mL for the 20-gram dose group). The total amount (or % dose) of butenafine HCl absorbed through the skin into the systemic circulation has not been quantitated. It was determined that the primary metabolite in urine was formed through hydroxylation at the terminal t-butyl side-chain.

In 11 patients with tinea pedis, Mentax® Cream, 1%, was applied by the patients to cover the affected and immediately surrounding skin area once daily for 4 weeks and a single blood sample was collected between 10 and 20 hours following dosing at 1, 2 and 4 weeks after treatment. The plasma butenafine HCl concentration ranged from undetectable to 0.3 ng/mL.

In 24 patients with tinea cruris, Mentax® Cream, 1%, was applied by the patients to cover the affected and immediately surrounding skin area once daily for 2 weeks (mean average daily dose: 1.3 ± 0.2 g). A single blood sample was collected between 0.5 and 65 hours after the last dose, and the plasma butenafine HCl concentration ranged from undetectable to 2.52 ng/mL (mean ± SD: 0.91 ± 0.15 ng/mL). Four weeks after cessation of treatment, the plasma butenafine HCl concentration ranged from undetectable to 0.28 ng/mL.

Microbiology

Butenafine HCl is a benzylamine derivative with a mode of action similar to that of the allylamine class of antifungal drugs. Butenafine HCl is hypothesized to act by inhibiting the epoxidation of squalene, thus blocking the biosynthesis of ergosterol, an essential component of fungal cell membranes. The benzylamine derivatives, like the allylamines, act an earlier step in the ergosterol biosynthesis pathway than the azole class of antifungal drugs. Depending on the concentration of the drug and the fungal species tested, butenafine HCl may be fungicidal or fungistatic in vitro. However, the clinical significance of these in vitro data is unknown.

Butenafine HCl has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS section:

Epidermophyton floccosum
Malassezia furfur
Trichophyton mentagrophytes
Trichophyton rubrum
Trichophyton tonsurans

Clinical Studies

Interdigital Tinea Pedis

Once Daily Four Week Dosing

In the following data presentations, patients with interdigital tinea pedis in the absence of moccasin-type tinea pedis and onychomycosis were studied. The term “Mycological Cure” is defined as both negative KOH and culture. The term “Effective Treatment” refers to patients who had a “Mycological Cure” and an Investigator's Global of either “Excellent” (80% to 99% improvement) or “Cleared” (100% improvement). The term “Overall Cure” refers to patients who had both a “Mycological Cure” and an Investigator's Global Assessment of “Cleared”(100% improvement).

Data from the two controlled studies in which Mentax® Cream, 1%, was used once daily for 4 weeks have been combined in the table below. Patients were treated for 4 weeks and evaluated 4 weeks post-treatment. In the “per protocol” analysis shown in the table below, statistical significance (Mentax® vs. vehicle) was assessed 4 weeks post-treatment.

Interdigital Tinea Pedis: 4-Week Dosing Regimen

Patient Outcome Category	WEEK 4 (End of Treatment)		WEEK 8 (4 Weeks Post-Treatment)
	Butenafine	Vehicle	Butenafine	Vehicle
Mycological Cure	89% (83/93)	57% (51/90)	90% (66/73)	38% (25/66)
Effective Treatment	57% (53/93)	28% (25/90)	74% (54/73)	26% (17/66)
Overall Cure	15% (14/93)	8% (7/90)	25% (18/73)	9% ( 6/66)

Twice-Daily One Week Dosing

In the following data presentations, patients with interdigital tinea pedis in the absence of moccasin-type tinea pedis were studied. Patients with concurrent onychomycosis were not excluded. The term “Mycological Cure” is defined as both negative KOH and culture. The term “Effective Treatment” refers to patients who had a “Mycological Cure” and an Investigator's Global of either “Excellent” (90% to 99% improvement) or “Cleared” (100% improvement). The term “Overall Cure” refers to patients who had both a “Mycological Cure” and an Investigator's Global Assessment of “Cleared” (100% improvement).

Data from the two controlled studies in which Mentax® Cream, 1%, was used twice daily for 1 week have been combined in the table below. Patients were treated for 1 week and evaluated 5 weeks post-treatment. In the “modified-intent-to-treat” analysis shown in the table below, statistical significance (Mentax® vs. vehicle) was assessed 5 weeks post-treatment.

Interdigital Tinea Pedis: 1-Week Dosing Regimen

Patient Outcome Category	WEEK 1 (End of Treatment)		WEEK 6 (5 Weeks Post-Treatment)
	Butenafine	Vehicle	Butenafine	Vehicle
Mycological Cure	44% (111/253)	28% (75/265)	79% (200/253)	20% (54/265)
Effective Treatment	5% (12/253)	3% (7/265)	38% (95/253)	7% (18/265)
Overall Cure	0.4% (1/253)	0.4% (1/265)	*15% (37/253)	0.7% (2/265)
* The Overall Cure Rate of 15% is calculated from a 9% rate in one trial and a 20% rate in the second trial.

Tinea Corporis and Tinea Cruris

In the following data presentations, patients with tinea corporis or tinea cruris were studied. The term “Mycological Cure” is defined as both negative KOH and culture. The term “Effective Treatment” refers to patients who had a “Mycological Cure” and an Investigator's Global of either “Excellent” (90% to 99% improvement) or “Cleared” (100% improvement). The term “Overall Cure” refers to patients who had both a “Mycological Cure” and an Investigator's Global Assessment of “Cleared”(100% improvement).

Separate studies compared Mentax® Cream to vehicle applied once daily for 2 weeks in the treatment of tinea corporis and tinea cruris. Patients were treated for 2 weeks and evaluated 4 weeks post-treatment. All subjects with a positive baseline exam (including positive culture and KOH) and who were dispensed medication were included in the “modified intent-to-treat” analysis shown in the table below. Statistical significance (Mentax® vs. vehicle) was achieved for all patient outcome categories at Week 2 (end of treatment) and Week 6 (4 weeks post-treatment).

Tinea Corporis

Patient Outcome Category	WEEK 2 (End of Treatment)		WEEK 6 (4 Weeks Post-Treatment)
	Butenafine	Vehicle	Butenafine	Vehicle
Mycological Cure	88% (37/42)	28% (10/36)	88% (37/42)	17% (6/36)
Effective Treatment	60% (25/42)	17% (6/36)	81% (34/42)	14% (5/36)
Overall Cure	31% (13/42)	3% (1/36)	67% (28/42)	14% (5/36)

Tinea Cruris

Patient Outcome Category	WEEK 2 (End of Treatment)		WEEK 6 (4 Weeks Post-Treatment)
	Butenafine	Vehicle	Butenafine	Vehicle
Mycological Cure	78% (29/37)	11% (4/38)	81% (30/37)	13% (5/39)
Effective Treatment	57% (21/37)	8% (3/39)	73% (27/37)	5% (2/39)
Overall cure	32% (12/37)	8% (3/39)	62% (23/37)	3% (1/39)

Tinea (pityriasis) versicolor

In the following data presentations, patients with tinea (pityriasis) versicolor were studied. The term “Negative Mycology” is defined as absence of hyphae in a KOH preparation of skin scrapings, i.e.; no fungal forms seen or the presence of yeast cells (blastospores) only. The term “Effective Treatment” is defined as Negative Mycology plus total signs and symptoms score (on a scale from zero to three) for erythema, scaling, and pruritus equal to or less than 1 at Week 8. The term “Complete Cure” refers to patients who had negative mycology plus sign/symptoms scores of zero for erythema, scaling, and pruritus.

Two separate studies compared Mentax® Cream to vehicle applied once daily for 2 weeks in the treatment of tinea (pityriasis) versicolor. Patients were treated for 2 weeks and were evaluated at the following weeks post-treatment: 2 (Week 4) and 6 (Week 8). All subjects with a positive baseline KOH and who were dispensed medications were included in the “intent-to-treat” analysis shown in the table below. Statistical significance (Mentax® vs. vehicle) was achieved for Effective Treatment, but not Complete Cure at 6 weeks post-treatment in Study 31. Marginal statistical significance (p = 0.051) (Mentax® vs. vehicle) was achieved for Effective Treatment but not Complete Cure at 6 weeks post-treatment in Study 32. Data from these two controlled studies are presented in the table below.

Tinea Veriscolor

Proportion (%) of responders in pivotal clinical trials (all randomized patients)
Patient Response Category	Week@	Study 31		Study 32
		Butenafine	Vehicle	Butenafine	Vehicle
Complete Cure *	2	41/87 (47%)	11/40 (28%)	29/85 (34%)	12/41 (29%)
	4	43/86 (50%)	15/42 (36%)	36/83 (43%)	13/41 (32%)
	8	44/87 (51%)	15/42 (36%)	30/86 (35%)	10/43 (23%)
Effective Treatment**	2	56/87 (64%)	16/40 (40%)	46/85 (54%)	16/41 (39%)
	4	50/86 (58%)	19/42 (45%)	45/83 (54%)	16/41 (39%)
	8	48/87 (55%)	15/42 (36%)	37/86 (43%)	11/43 (26%)
Negative Mycology ***	2	57/87 (66%)	20/40 (50%)	57/85 (67%)	21/41 (51%)
	4	51/86 (59%)	20/42 (48%)	52/83 (63%)	18/41 (44%)
	8	48/87 (55%)	15/42 (36%)	43/86 (50%)	12/43 (28%)
@ Week 2 (end of treatment), Week 4 (2 weeks post-treatment), and Week 8 (6 weeks post-treatment) * Negative Mycology plus absence of erythema, scaling, and pruritus ** Negative Mycology plus no or minimal involvement of erythema, scaling, or pruritus *** Absence of hyphae in a KOH preparation of skin scrapings, i.e., no fungal forms seen or the presence of yeast cells (blastospores) only

Tinea (pityriasis) versicolor is a superficial, chronically recurring infection of the glabrous skin caused by Malassezia furfur (formerly Pityrosporum orbiculare). The commensal organism is part of the normal skin flora. In susceptible individuals the condition may give rise to hyperpigmented or hypopigmented patches on the trunk which may extend to the neck, arms and upper thighs. Treatment of the infection may not be immediately result in restoration of pigment to the affected sites. Normalization of pigment following successful therapy is variable and may take months, depending upon individual skin type and incidental sun exposure. The rate of recurrence of infection is variable.

Last updated on RxList: 4/3/2009

The patient should be instructed to:

1. Use Mentax® Cream, 1%, as directed by the physician. The hands should be washed after applying the medication to the affected area(s). Avoid contact with the eyes, nose, mouth, and other mucous membranes. Mentax® Cream, 1%, is for external use only.
2. Dry the affected area(s) thoroughly before application, if you wish to apply Mentax® Cream, 1%, after bathing.
3. Use the medication for the full treatment time recommended by the physician, even though symptoms may have improved. Notify the physician if there is no improvement after the end of the prescribed treatment period, or sooner, if the condition worsens (see below).
4. Inform the physician if the area of application shows signs of increased irritation, redness, itching, burning, blistering, swelling, or oozing.
5. Avoid the use of occlusive dressings unless otherwise directed by the physician.
6. Do not use this medication for any disorder other than that for which it was prescribed.

Last updated on RxList: 4/3/2009

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

BUTENAFINE CREAM - TOPICAL

(byou-TEN-uh-feen)

COMMON BRAND NAME(S): Mentax

USES: This medication is used to treat a variety of fungal skin infections such as ringworm, athlete's foot, and jock itch. This medication is also used to treat a skin condition known as pityriasis (tinea versicolor), a fungal infection that causes a lightening or darkening of the skin of the neck, chest, arms, or legs. Butenafine is an antifungal that works by preventing the growth of fungus.

Do not use this medication for the treatment of fungal nail infections.

HOW TO USE: Use this medication on the skin only. Clean and thoroughly dry the area to be treated. Apply a thin layer of the medication to and around the affected area and gently rub in, usually 1 to 2 times daily as directed on the product package. If you are uncertain about any of the information, consult your doctor or pharmacist. If your doctor has prescribed this medication to you, then use as directed. Wash your hands after using unless the area to be treated includes the hands. Do not wrap, cover, or bandage the area unless directed to do so by your doctor.

Do not apply the medication in the eyes, nose, or mouth, inside the vagina, or on the scalp. If you do get the medication in those areas, flush with plenty of water.

The dosage and length of treatment depends on the type of infection being treated.

Do not apply more often or use longer than directed. This may increase the risk of side effects.

Use this medication regularly to get the most benefit from it. To help you remember, use it at the same time(s) each day.

Continue to use this medication until the full treatment period is finished, even if symptoms disappear after a few days. Stopping the medication too early may result in a return of the infection.

Inform your doctor if your condition worsens or does not improve after the treatment period.

SIDE EFFECTS: Burning, irritation, redness, or itching at the application site may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

If your doctor has prescribed this medication, remember that he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: blistering/swelling/oozing at the application site.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using this medication, tell your doctor or pharmacist if you are allergic to butenafine; or to allylamine antifungals (e.g., naftifine, terbinafine); or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: athlete's foot on the bottom/side of the foot.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: If you are taking this medication under your doctor's direction, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: drugs that weaken the immune system (e.g., cyclosporine, corticosteroids such as prednisone).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: This medication may be harmful if swallowed. If overdose or swallowing is suspected, contact your local poison control center or emergency room immediately. US residents should call the US National Poison Hotline at 1-800-222-1222. Canada residents should call a provincial poison control center.

NOTES: Do not share this medication with others.

If your doctor has directed you to use this medication, use it for your current condition only. Do not use it later for another infection unless told to do so by your doctor. A different medication may be necessary in that case.

If you are treating athlete's foot, make sure to wear well-fitting, ventilated shoes. Also, change shoes and socks at least once daily.

When this medication is used to treat pityriasis, your normal skin color may not return immediately. It may take several months after treatment is completed for your natural skin color to return.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature away from light and heat. Consult your pharmacist or product labeling for exact temperature range. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.