Butenafine is a topical antifungal indicated for the treatment of tinea corporis, tinea cruris, tinea pedis, and tinea versicolor. Butenafine use for tinea versicolor was not studied in immunocompromised persons. It is not for use on the nails or scalp or for vaginal yeast infections. Butenafine is a member of the class of antifungal compounds known as benzylamines which are structurally related to the allylamines. The benzylamine derivatives, like the allylamines, act at an earlier step in the ergosterol biosynthesis pathway than the azole class of antifungal drugs. Butenafine blocks the biosynthesis of ergosterol, an essential component of fungal cell membrane, by inhibiting the epoxidation of squalene by squalene monooxygenase. Cross reactivity may occur in persons who are known to be sensitive to allylamine antifungals. The most frequently reported adverse events in uncontrolled clinical trials include contact dermatitis, erythema, pruritus, and skin irritation.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Topical Administration
Cream/Ointment/Lotion Formulations
-For external use only.
-Avoid contact with the eyes, nose, mouth, or other mucus membranes.
-Cleanse the affected skin with soap and water and dry the affected area(s) thoroughly before application.
-Wash hands after applying the medication.
-Avoid use of occlusive dressings.
-For tinea pedis, change shoes and socks at least once daily. Wear well-fitting, ventilated shoes.
In uncontrolled clinical trials, the most frequently reported adverse events (less than 2%) in subjects treated with butenafine include contact dermatitis, erythema, pruritus, and skin irritation. In controlled clinical trials, approximately 1% of subjects reported dermatologic adverse events, including burning/stinging, itching, and worsening of the condition. If irritation or sensitivity develops with the use of butenafine, discontinue treatment and institute appropriate therapy.
Butenafine is contraindicated in persons who have a known or suspected hypersensitivity to the butenafine or any of its components.
Butenafine is for external use only. It is not for ophthalmic administration, oral administration, or vaginal administration. Avoid contact of butenafine with the eyes, nose, mouth, or other mucous membranes. If accidental ocular exposure occurs, rinse the eye(s) thoroughly with water.
Do not use butenafine for onychomycosis, tinea capitis, or vaginal candidiasis.
Use butenafine with caution during pregnancy. There are no adequate and well-controlled studies that have been conducted with topical butenafine during human pregnancy. In studies performed in rats and rabbits utilizing oral terbinafine at doses that were up to 16-times the maximum recommended human dose for tinea versicolor based on body surface area (BSA) comparisons, no treatment-related external, visceral, skeletal malformations or variations or treatment-related effects on postnatal survival, development of the F1 generation or their subsequent maturation and fertility were observed. Additionally, teratogenicity was not observed in rats after administration of subcutaneous butenafine during organogenesis at doses equivalent to 0.5-times the maximum recommended human dose for tinea versicolor based on BSA comparisons.
It is not known if butenafine is excreted in human milk. Because many drugs are excreted in human milk, use caution when using butenafine during breast-feeding.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Epidermophyton floccosum, Malassezia furfur, Trichophyton mentagrophytes, Trichophyton rubrum, Trichophyton tonsurans
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
This drug may also have activity against the following microorganisms: Candida albicans, Candida sp., Microsporum canis, Trichophyton violaceum
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.
For the treatment of tinea corporis, tinea cruris, and tinea versicolor:
Topical dosage:
Adults: Apply to the affected skin area(s) and immediately surrounding skin once daily for 2 weeks. If no improvement is seen within 2 weeks, reassess diagnosis.
Children and Adolescents 12 to 17 years: Apply to the affected skin area(s) and immediately surrounding skin once daily for 2 weeks. If no improvement is seen within 2 weeks, reassess diagnosis.
For the treatment of interdigital tinea pedis:
Topical dosage:
Adults: Apply to the affected skin area(s) between and around the toes once daily for 4 weeks or twice daily for 7 days (morning and night). Effectiveness on the bottom or sides of the foot is unknown.
Children and Adolescents 12 to 17 years: Apply to the affected skin area(s) between and around the toes once daily for 4 weeks or twice daily for 7 days (morning and night). Effectiveness on the bottom or sides of the foot is unknown.
Maximum Dosage Limits:
-Adults
2 applications/day topically.
-Geriatric
2 applications/day topically.
-Adolescents
2 applications/day topically.
-Children
12 years: 2 applications/day topically.
1 to 11 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Butenafine products.
Butenafine is a benzylamine derivative antifungal that acts by inhibiting the epoxidation of squalene, thus blocking the biosynthesis of ergosterol, an essential component of fungal cell membranes. Depending on the concentration of the drug and the fungal species tested, butenafine may be fungicidal or fungistatic.
Butenafine is administered topically. Low concentrations of butenafine may persist in the plasma for 4 weeks or more after last application. The primary metabolite found in the urine is formed through hydroxylation at the terminal t-butyl side-chain.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Topical Route
There is some systemic absorption after topical application of butenafine; however, the total dose (% dose) absorbed through the dermis into the systemic circulation has not been quantified. In 11 subjects with tinea pedis, butenafine 1% cream was applied 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 after dosing at 1, 2, and 4 weeks after treatment. The plasma butenafine concentration ranged from undetectable to 0.3 ng/mL. In 24 subjects with tinea cruris, butenafine 1% cream was applied to cover the affected and immediately surrounding skin area once daily for 2 weeks (mean average daily dose: 1.3 +/- 0.2 g), and a single blood sample was collected between 0.5 and 65 hours after the last dose. The plasma butenafine concentration ranged from undetectable to 2.52 ng/mL. At 4 weeks after treatment discontinuation, the plasma butenafine concentration ranged from undetectable to 0.28 ng/mL. In another study in healthy subjects, 6 g of butenafine 1% cream was applied once daily to the dorsal skin (3,000 cm2) and 20 g was applied once daily to the arms, trunk, and groin areas (10,000 cm2) for 14 days. After 14 days, the 6-g dose group (n = 7) had a mean peak plasma concentration (Cmax) of 1.4 +/- 0.8 ng/mL, a mean time to peak plasma concentration (Tmax) of 15 +/- 8 hours, and a mean systemic exposure (AUC) of 23.9 +/- 11.3 ng x hour/mL. For the 20-g dose group (n = 12), the mean Cmax was 5 +/- 2 ng/mL, mean Tmax was 6 +/- 6 hours, and mean AUC was 87.8 +/- 45.3 ng x hour/mL. A biphasic decline of plasma butenafine concentrations was observed with the half-lives estimated to be 35 hours and more than 150 hours, respectively. Low concentrations (mean 0.1 +/- 0.2 ng/mL for the 6-g dose group and 0.7 +/- 0.5 ng/mL for the 20-g dose group) of butenafine were found in the systemic circulation at 7 days after last application.