Butenafine - Drug Monograph

Introduction

Butenafine hydrochloride is a synthetic benzylamine antifungal agent used topically for the treatment of various superficial fungal infections. First approved by the FDA in the 1990s, it belongs to the allylamine class of antifungals and demonstrates broad-spectrum activity against dermatophytes, yeasts, and other fungi. Butenafine is available in various formulations including creams, gels, and sprays, typically in 1% concentration.

Mechanism of Action

Butenafine exerts its antifungal effect through inhibition of squalene epoxidase, a key enzyme in the ergosterol biosynthesis pathway. This inhibition leads to accumulation of squalene and depletion of ergosterol in fungal cell membranes. Ergosterol is an essential component of fungal cell membranes, and its deficiency results in increased membrane permeability and disruption of cellular functions, ultimately leading to fungal cell death. Butenafine demonstrates both fungicidal and fungistatic activity depending on the concentration and fungal species.

Indications

FDA-approved indications:

• Tinea pedis (athlete's foot)
• Tinea corporis (ringworm)
• Tinea cruris (jock itch)
• Tinea versicolor (caused by Malassezia furfur)

Off-label uses:

• Cutaneous candidiasis
• Onychomycosis (as adjunctive therapy)

Dosage and Administration

• Apply a thin layer to affected area once or twice daily
• Tinea pedis: Apply twice daily for 7 days or once daily for 4 weeks
• Tinea corporis/cruris: Apply once daily for 2 weeks
• Tinea versicolor: Apply once daily for 2 weeks

• Clean and dry affected area before application
• Wash hands after application unless treating hands
• For intertriginous areas, apply sparingly

• Pediatric use: Safety established in children ≥12 years
• Geriatric use: No dosage adjustment required
• Renal/hepatic impairment: No specific recommendations (minimal systemic absorption)

Pharmacokinetics

Contraindications

• Hypersensitivity to butenafine or any component of the formulation
• History of allergic reactions to other allylamine antifungals

Warnings and Precautions

• For external use only; avoid contact with eyes, nose, mouth, and other mucous membranes
• Discontinue if irritation or hypersensitivity develops
• Not for ophthalmic use
• Use with caution in patients with pre-existing skin conditions or compromised skin barrier
• Superinfections with nonsusceptible organisms may occur
• Pregnancy Category B: Use only if clearly needed (limited human data)
• Lactation: Caution advised; unknown if excreted in human milk

Drug Interactions

• No clinically significant systemic drug interactions documented (due to minimal absorption)
• Theoretical potential for interactions with other topically applied medications
• Avoid concurrent use with other topical products that may cause skin irritation

Adverse Effects

• Application site reactions: burning, stinging, itching
• Local irritation: erythema, dryness
• Contact dermatitis

• Skin cracking
• Blistering
• Swelling
• Allergic reactions

• Severe hypersensitivity reactions
• Skin discoloration

Monitoring Parameters

• Clinical response: improvement in signs and symptoms
• Local skin reactions: erythema, irritation, pruritus
• Signs of superinfection
• Patient compliance with treatment regimen
• Resolution of infection at follow-up (typically 2-4 weeks post-treatment)

Patient Education

• Use medication exactly as prescribed; complete full course of treatment
• Wash hands before and after application
• Keep affected areas clean and dry
• Avoid tight-fitting clothing over treated areas
• Do not cover treated area with occlusive dressings unless directed
• Report any signs of worsening condition or skin irritation
• Store at room temperature; avoid extreme temperatures
• Do not share medication with others
• Continue treatment for prescribed duration even if symptoms improve
• Seek medical attention if no improvement after 4 weeks of treatment

References

1. Gupta AK, Shear NH. Butenafine: a review of its antifungal activity and clinical efficacy in the management of superficial fungal infections. Drugs. 1997;53(5):862-872. 2. FDA Prescribing Information: Butenafine Hydrochloride Cream. 3. Elewski BE. Mechanisms of action of systemic antifungal agents. J Am Acad Dermatol. 1993;28(5 Pt 1):S28-S34. 4. Lesher JL Jr. Butenafine hydrochloride: a new benzylamine antifungal. J Am Acad Dermatol. 1997;37(2 Pt 1):S15-S19. 5. McClellan KJ, Wiseman LR, Markham A. Butenafine: a review of its antimicrobial activity and therapeutic use in superficial mycoses. Drugs. 1999;58(2):375-390. 6. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 14th Edition. 7. ClinicalTrials.gov: Butenafine efficacy studies.