ATC Class:D01AE23
VA Class:DE102
Butenafine hydrochloride is a synthetic benzylamine antifungal agent.1, 2, 3, 4, 5, 7, 8, 9, 10, 11
Butenafine hydrochloride is used topically for the treatment of certain dermatophytoses, including tinea corporis (body ringworm), tinea cruris (jock itch), and tinea pedis (athlete's foot), caused by Epidermophyton floccosum , Trichophyton mentagrophytes , T. rubrum , or T. tonsurans .1, 7, 8, 9, 18 The drug may be used topically for self-medication for the treatment of these dermatophyte infections.18
Topical butenafine should not be used for the treatment of dermatophyte infections of the scalp or nails.18
Efficacy of topical butenafine has only been established in immunocompetent patients to date.1
Butenafine hydrochloride is as active as clotrimazole,3, 4, 5, 11 tolnaftate,4, 5, 7, 11 terbinafine,6 or naftifine4, 5, 9, 11 against experimentally induced T. mentagrophytes in guinea pigs.
Tinea Corporis and Tinea Cruris
Tinea corporis and tinea cruris generally can be effectively treated using a topical antifungal; however, an oral antifungal may be necessary if the disease is extensive, dermatophyte folliculitis is present, the infection is chronic or does not respond to topical therapy, or the patient is immunocompromised because of coexisting disease or concomitant therapy.12, 13, 14, 15, 16
Many clinicians consider topical imidazole-derivative azole antifungals (e.g., clotrimazole, econazole, ketoconazole, miconazole, oxiconazole, sulconazole) or topical allylamine antifungals (e.g., naftifine, terbinafine) the drugs of first choice for the topical treatment of tinea corporis or tinea cruris,13, 17 although other antifungals (e.g., ciclopirox olamine, butenafine hydrochloride, tolnafate, undecylenic acid) also can be effective in the treatment of these infections.12, 13, 14, 15, 16
In a placebo-controlled study in patients with tinea corporis, butenafine hydrochloride 1% cream applied once daily for 2 weeks resulted in a mycologic cure in 88% of patients both at the completion of therapy and 4 weeks later; the corresponding mycologic cure rates for vehicle placebo were 28 and 17%, respectively.1
In a clinical study in patients with tinea cruris, 2 weeks of therapy with butenafine hydrochloride 1% cream applied once daily resulted in a mycologic cure in 78% of patients at the completion of therapy and 81% 4 weeks later; the corresponding response rates for vehicle placebo were 11 and 13%, respectively.8
Uncomplicated interdigital and vesiculobullous forms of tinea pedis generally can be treated effectively using a topical imidazole-derivative azole antifungal (e.g., clotrimazole, econazole, ketoconazole, miconazole, oxiconazole, sulconazole), an allylamine antifungal (e.g., naftifine, terbinafine), or other topical antifungal such as ciclopirox olamine, butenafine hydrochloride, tolnaftate, or undecylenic acid.12, 13, 14, 15, 16 However, an oral antifungal usually is necessary for the treatment of hyperkeratotic areas on the palms and soles,13, 16 and for chronic moccasin-type (dry-type) tinea pedis,12, 13, 15 and for the treatment of tinea unguium (fingernail or toenail dermatophyte infections, onychomycosis).12, 13, 15
In a clinical trial in patients with interdigital tinea pedis, 4 weeks of once-daily therapy with butenafine hydrochloride 1% cream or vehicle placebo resulted in mycologic cure in 88 or 45% of patients, respectively, at the completion of therapy and in 88 or 33% of patients, respectively, 4 weeks later.7 In other placebo-controlled trials involving patients with interdigital tinea pedis (patients with either chronic moccasin-type tinea pedis or onychomycosis were excluded), mycologic cure was achieved in 89 or 57% of patients after 4 weeks of therapy with butenafine hydrochloride 1% cream or placebo, respectively, and in 90 and 38% of patients, respectively, 4 weeks later.1 The mycologic response to a 1-week regimen involving twice-daily application of butenafine hydrochloride was slightly less than that reported with a 4-week, once-daily regimen.1 In 2 placebo-controlled trials involving patients with interdigital tinea pedis (patients with chronic moccasin-type tinea pedis were excluded but patients with onychomycosis were not excluded), 1 week of therapy with butenafine hydrochloride 1% cream administered twice daily resulted in a mycologic cure in 44% of patients at the end of treatment and 79% 5 weeks later; the corresponding mycologic cure rates in those receiving vehicle placebo were 28 and 20%, respectively.1 In another study in patients with interdigital tinea pedis, 1 week of therapy with butenafine hydrochloride 1% cream administered twice daily resulted in mycologic cure in 61% 1 week after the completion of therapy and 74% 4 weeks later; the corresponding response rates for vehicle placebo were 35 and 22%, respectively.9
Butenafine hydrochloride is used topically for the treatment of pityriasis (tinea) versicolor, a superficial infection caused by Malassezia furfur ( Pityrosporum orbiculare or P. ovale ).1
Efficacy of topical butenafine has only been established in immunocompetent patients to date.1
Pityriasis versicolor generally can be treated topically with an imidazole-derivative azole antifungal (e.g., clotrimazole, econazole, ketoconazole, miconazole, oxiconazole, sulconazole), an allylamine antifungal (e.g., terbinafine), ciclopirox olamine, or certain other topical therapies (e.g., selenium sulfide 2.5%).12, 15, 19, 20 However, an oral antifungal (e.g., itraconazole, ketoconazole) may be indicated, with or without a topical antifungal, in patients who have extensive or severe infections or who fail to respond to or have frequent relapses with topical therapy.
In clinical studies in patients with pityriasis (tinea) versicolor receiving 2 weeks of therapy with butenafine hydrochloride 1% cream, “effective treatment” (defined as negative mycology [observation of no fungal forms or of yeast only in lesion scrapings prepared with potassium hydroxide] and a total signs-and-symptoms score [on a scale from 0 to 3] for erythema, scaling, and pruritus of 1 or less) was reported in 54-64% of patients at the end of therapy and in 43-55% of patients at the end of the study (6 weeks after completion of therapy); the corresponding effective treatment rates for those receiving vehicle placebo were 39-40% and 26-36%, respectively.1 Complete cure (defined as negative mycology and a total signs-and-symptoms score of 0) was reported at the end of therapy in 34-47% of patients receiving butenafine compared with 28-29% of those receiving vehicle placebo.1 Complete cure rates at the end of the study did not differ between patients receiving butenafine or vehicle placebo (35-51 or 23-36%, respectively).1
Butenafine hydrochloride is applied topically to the skin as a 1% cream.1, 18
Butenafine cream should not be applied to eyes.1, 18 Contact with the mouth, eyes, and other mucous membranes should be avoided.1, 18
Butenafine should not be applied to scalp or nail infections.18
Prior to application of the cream, the affected areas should be cleansed with soap and water and dried thoroughly.1, 18 The cream is then applied and massaged gently into the affected areas.1, 18 Hands should be washed after the application process.1, 18
Occlusive dressings or wrappings should not be used.1
When used for the treatment of interdigital tinea pedis (athlete's foot), special attention should be paid to applying to spaces between the toes.18 In addition, patients with tinea pedis should wear well-fitting, ventilated shoes and change their shoes and socks at least once daily.18
Tinea Corporis and Tinea Cruris
For the topical treatment of tinea corporis (body ringworm) or tinea cruris (jock itch), including self-medication , in adults and children 12 years of age or older, a sufficient amount of butenafine hydrochloride 1% cream should be applied to the cleansed affected area and immediately surrounding skin once daily for 2 weeks.1, 18
If clinical improvement does not occur after the treatment period, the diagnosis and therapy should be reevaluated.1
For the topical treatment of interdigital tinea pedis (athlete's foot), including self-medication , in adults and children 12 years of age or older, a sufficient amount of butenafine hydrochloride 1% cream should be applied to the cleansed affected area and immediately surrounding skin twice daily (morning and night) for 7 days or once daily for 4 weeks.1, 18 Some evidence suggests that the 1-week regimen is less effective than the 4-week regimen for the treatment of tinea pedis.1 (See Uses.) This difference in efficacy should be considered when selecting a dosage regimen for the treatment of tinea pedis in patients at risk for the development of bacterial cellulitis of the lower extremity associated with interdigital cracking/fissuring.1
If clinical improvement does not occur after the treatment period, the diagnosis and therapy should be reevaluated.1
For the topical treatment of pityriasis (tinea) versicolor in adults and children 12 years of age or older, a sufficient amount of butenafine hydrochloride 1% cream should be applied to the cleansed affected area and immediately surrounding skin once daily for 1-2 weeks.1
If clinical improvement does not occur after the treatment period, the diagnosis and therapy should be reevaluated.1
Known hypersensitivity to butenafine or any ingredient in the formulation.1
For external use only.1, 18 Use only for topical application to the skin; not for ophthalmic or intravaginal use.1, 18
Avoid contact with eyes, nose, mouth, and other mucous membranes.1
If contact with the eye(s) occurs, the eye(s) should be washed with large amounts of water.18 The patient should consult a clinician if ocular irritation persists.18
Do not use for scalp or nail infections.18
If irritation or sensitivity occurs, discontinue drug and initiate appropriate therapy.1
Contact dermatitis has been reported rarely.1
Use with caution in patients hypersensitive to allylamine antifungals (e.g., naftifine, terbinafine) since cross-sensitivity may occur.1
Selection and Use of Antifungals
Prior to initiation of butenafine treatment, the diagnosis should be confirmed by direct microscopic examination of scrapings from infected tissue mounted in potassium hydroxide (KOH) or by culture using an appropriate medium.1
Category B.1 (See Users Guide.)
Not known whether butenafine is distributed into milk following topical administration.1 Use with caution and avoid applying the drug to the breast of nursing women.1
Safety and efficacy not established in children younger than 12 years of age.1, 18 Use in children 12-16 years of age is supported by evidence from adequate and well-controlled studies in adults.1
Burning/stinging, itching, and worsening of condition reported in 1% of patients in clinical studies.1
Butenafine hydrochloride is a synthetic benzylamine antifungal agent.1, 2, 3, 4, 5, 7, 8, 9, 10, 11 Butenafine is structurally and pharmacologically5 related to allylamine antifungals (e.g., naftifine, terbinafine).1, 4, 7, 8, 9, 10, 11
The exact mechanism of action of butenafine's antifungal activity has not been fully determined.1 Butenafine presumably exerts its antifungal activity by altering cellular membranes, resulting in increased membrane permeability, and growth inhibition.1, 2, 3, 11 Although the exact mechanism of action of butenafine has not been fully determined, it has been suggested that the antifungal activity of the drug may result from interference with ergosterol synthesis.1, 2, 4, 7, 8, 9, 11 The drug appears to interfere with sterol biosynthesis by inhibiting the enzyme squalene monooxygenase (squalene 2,3-epoxidase),10 which results in decreased amounts of sterols, especially ergosterol,2, 4, 8, 9, 11 and a corresponding accumulation of squalene (the usual substrate of the enzyme) in the cells.7, 11 Butenafine, like allylamine derivatives, appears to affect sterol biosynthesis at an earlier stage than do imidazole derivatives.1, 4, 7, 8, 9, 11
Butenafine may be fungicidal in certain concentrations or against susceptible organisms (e.g., dermatophytes).1, 4, 5, 7, 8, 9, 10, 11 Butenafine is active in vitro against Epidermophyton floccosum , Microsporum canis ,4, 5, 11 Trichophyton mentagrophytes , T. rubrum ,1, 3, 4, 5, 11 Malassezia furfur ( Pityrosporum orbiculare or P. ovale ),1 and Sporothrix schenckii .2 The drug also is active against some yeasts, including Candida albicans and C. parapsilosis .2, 7, 11
Importance of completing full course of treatment, even if symptoms improve.1, 18
Importance of contacting clinician if improvement does not occur by end of prescribed treatment period.1
Importance of notifying clinician if condition worsens or treated area shows signs of increased irritation, redness, itching, burning, blistering, swelling, or oozing.1, 18
Importance of applying to affected areas as directed and avoiding contact with eyes, nose, mouth, or other mucous membranes.1, 18
Advise patients to wash their hands after touching the affected areas so that the infection is not spread to other areas of the body or to other individuals.1, 18
For patients with tinea pedis (athlete's foot), importance of wearing well-fitting, ventilated shoes and changing socks at least once daily.18
Importance of not using occlusive dressings, unless otherwise directed by clinician.1
Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs.1
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Additional Information
Overview® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Topical | Cream | 1% | Lotrimin® Ultra® | Schering-Plough |
Mentax® | Mylan |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions January 1, 2008. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Bertek Pharmaceuticals Inc. Mentax® (butenafine HCl) cream, 1% prescribing information. Morgantown, WV; 2001 Jun 6.
2. Iwatani W, Arika T, Yamaguchi H. Two mechanisms of butenafine action in Candida albicans. Antimicrob Agents Chemother. 1993; 37:785-8.
3. Arika T, Hase T, Yokoo M. Anti- Trichophyton mentagrophytes activity and percutaneous permeation of butenafine in guinea pigs. Antimicrob Agents Chemother . 1993; 37:363-5. [PubMedCentral][PubMed 8452371]
4. Arika T, Yokoo M, Hase T et al. Effects of butenafine hydrochloride, a new benzylamine derivative, on experimental dermatophytosis in guinea pigs. Antimicrob Agents Chemother . 1990; 34:2250-53. [PubMedCentral][PubMed 2073116]
5. Arika T, Yokoo M, Maeda T et al. Effects of butenafine hydrochloride, a new benzylamine derivative, on experimental tinea pedis in guinea pigs. Antimicrob Agents Chemother . 1990; 34:2254-5. [PubMedCentral][PubMed 2073117]
6. Uchida K, Kudoh M, Yamaguchi H. A study on effectiveness of treatment and prevention of relapse using topical administration of terbinafine in a guinea pig model for tinea pedis. Jpn J Antibiot . 1994; 47:1407-12. [PubMed 7807700]
7. Tschen E, Elewski B, Gorsulowsky et al. Treatment of interdigital tinea pedis with a 4-week once-daily regimen of butenafine hydrochloride 1% cream. J Am Acad Dermatol . 1997; 36:S9-14. [PubMed 9039199]
8. Lesher JL, Babel DE, Stewart DM et al. Butenafine 1% cream in the treatment of tinea cruris: a multicenter, vehicle-controlled, double-blind trial. J Am Acad Dermatol . 1997; 36:S20-4. [PubMed 9039201]
9. Savin R, De Villez RL, Elewski B et al. One-week therapy with twice-daily butenafine 1% cream versus vehicle in the treatment of tinea pedis: a multicenter, double-blind trial. J Am Acad Dermatol . 1997; 36:S15-19.
10. Odom RB. Update on topical therapy for superficial fungal infections: focus on butenafine. J Am Acad Dermatol . 1997; 36:S1-2.
11. Brennan B, Leyden JL. Overview of topical therapy for common superficial fungal infections and the role of new topical agents. J Am Acad Dermatol . 1997; 36:53-8. [PubMed 8996261]
12. Gupta AK, Einarson TR, Summerbell RC et al. An overview of topical antifungal therapy in dermatomycoses: a North American perspective. Drugs . 1998; 55:645-74. [PubMed 9585862]
13. Piérard GE, Arrese JE, Piérard-Franchimont C. Treatment and prophylaxis of tinea infections. Drugs . 1996; 52:209-24. [PubMed 8841739]
14. Lesher JL. Recent developments in antifungal therapy. Dermatol Clin . 1996; 14:163-9. [PubMed 8821170]
15. Hay RJ. Dermatophytosis and other superficial mycoses. In: Mandel GL, Douglas RG Jr, Bennett JE, eds. Principles and practices of infectious disease. 4th ed. New York: Churchill Livingston; 1995: 2375-86.
16. Drake LA, Dincehart SM, Farmer ER et al. Guidelines of care for superficial mycotic infections of the skin: tinea corporis, tinea cruris, tinea faciei, tinea manuum, and tinea pedis. J Am Acad Dermatol . 1996; 34:282-6. [PubMed 8642094]
17. Reviewers' comments (personal observations) on Sulconazole 84:04.08.
18. Schering-Plough. Lotrimin® Ultra® (butenafine hydrochloride) 1% cream prescribing information. Memphis, TN; 2001.
19. Assaf RR. The superficial mycoses. Dermatol Clin . 1996; 14:57-67. [PubMed 8821158]
20. Drake LA, Dinehart SM, Farmer ER. Guidelines of care for superficial mycotic infections of the skin: pityriasis (tinea) versicolor. J Am Acad Dermatol . 1996; 34:287-9. [PubMed 8642095]