butenafine
Regulatory sources consulted
Approved indications
- Interdigital tinea pedis, tinea cruris, and tinea corporis.
Clinical warnings
- For external use only; do not use on nails, scalp, mouth, eyes, or for vaginal yeast infections. Effectiveness on the bottom or sides of the foot is unknown. — openFDA Butenafine hydrochloride cream 1% set ID 0841f741-6409-4d93-a6a7-901808f77bcd
- Stop use and ask a clinician if excessive irritation develops or the condition worsens. — openFDA Butenafine hydrochloride cream 1% set ID 0841f741-6409-4d93-a6a7-901808f77bcd
Pregnancy and lactation
The matching local label does not provide a specific pregnancy or breastfeeding recommendation.
Recent literature (PubMed)
Dermatophytosis remains one of the most common superficial fungal infections worldwide, and antifungal-resistant strains have recently emerged as an increasing clinical concern. In Japan, the prevalence of terbinafine-resistant Trichophyton species is currently estimated to be 2%, with most isolates harboring squalene epoxidase (SQLE) gene mutations such as Leu393Phe and Phe397Leu. This review summarizes recent epidemiological findings and representative clinical cases to illustrate the practical management strategies for antifungal-resistant dermatophytosis in Japan. Three illustrative cases were presented. Case 1 involved Trichophyton interdigitale carrying a Phe397Leu mutation that was unresponsive to terbinafine but was successfully treated with topical efinaconazole and luliconazole. Case 2 described a cluster infection of terbinafine-resistant Trichophyton rubrum (Leu393Phe) in a group home, where oral fosravuconazole achieved complete cure. Case 3 reported five soldiers with terbinafine-resistant dermatophytosis caused by Phe397Leu or Phe415Ile mutations, which were likely associated with prolonged topical SQLE inhibitor use. Resistance is often induced by the long-term or intermittent application of SQLE inhibitors, including over-the-counter topical terbinafine and butenafine. For suspected terbinafine-resistant infections, non-SQLE azoles, such as luliconazole and lanoconazole, are recommended because of their 10- to 100-fold increased activity against Trichophyton species. Oral fosravuconazole and topical agents such as 10% efinaconazole or 5% luliconazole have proven effective for onychomycosis. Ongoing surveillance, appropriate antifungal stewardship, and timely adjustment of treatment regimens are essential to prevent the further spread of antifungal-resistant dermatophytosis.
Allylamines, naftifine and terbinafine, and the benzylamine, butenafine, are antifungal agents with activity on the fungal cell membrane. These synthetic compounds specifically inhibit squalene epoxidase, a key enzyme in fungal sterol biosynthesis. This results in a deficiency in ergosterol, a major fungal membrane sterol that regulates membrane fluidity, biogenesis, and functions, and whose damage results in increased membrane permeability and leakage of cellular components, ultimately leading to fungal cell death. With the fungal cell membrane being predominantly made up of lipids including sterols, these lipids have a vital role in the pathogenesis of fungal infections and the identification of improved therapies. This review will focus on the fungal cell membrane structure, activity of allylamines and benzylamines, and the mechanistic damage they cause to the membrane. Furthermore, pharmaceutical preparations and clinical uses of these drugs, mainly in dermatophyte infections, will be reviewed.
Objective: To systematically review literature enabling the comparison of the efficacy of pharmaceutical treatments for tinea pedis in adults. Design: Systematic review of randomised controlled trials (RCTs) with mycological cure as the primary outcome. Secondary outcomes did include the clinical assessment of resolving infection or symptoms, duration of treatment, adverse events, adherence, and recurrence. Eligibility Criteria: Study participants suffering from only tinea pedis that were treated with a pharmaceutical treatment. The study must have been conducted using an RCT study design and recording age of the participant > 16 years of age. Results: A total of seven studies met the inclusion criteria, involving 1042 participants. The likelihood of resolution in study participants treated with terbinafine was RR 3.9 (95% CI: 2.0−7.8) times those with a placebo. Similarly, the allylamine butenafine was effective by RR 5.3 (95% CI: 1.4−19.6) compared to a placebo. Butenafine was similarly efficacious to terbinafine RR 1.3 (95% CI: 0.4−4.4). Terbinafine was marginally more efficacious than itraconazole, RR 1.3 (95% CI: 1.1−1.5). Summary/Conclusion: Topical terbinafine and butenafine treatments of tinea pedis were more efficacious than placebo. Tableted terbinafine and itraconazole administered orally were efficacious in the drug treatment of tinea pedis fungal infection. We are concerned about how few studies were available that reported the baseline characteristics for each treatment arm and that did not suffer greater than 20% loss to follow-up. We would like to see improved reporting of clinical trials in academic literature. Registration name: Treatment’s for athlete’s foot—systematic review with meta-analysis [CRD42020162078].