Butenafine

Butenafine is an antifungal agent belonging to the pharmacological class of Allylamine.

Butenafine has been approved to relieve symptoms and also for the treatment and maintenance of Tinea corporis/tinea cruris, Tinea pedis, Tinea versicolor.

The absorption of the drug through the skin into the bloodstream has not been quantified, and the volume of distribution and extent of protein binding are not available. Regarding metabolism, the primary metabolite identified in urine is formed through hydroxylation at the terminal t-butyl side-chain. Further research is needed to fully understand these pharmacokinetic aspects of the drug.

The common side effects involved in using Butenafine are redness, Burning, Stinging, Irritation, Itching at the application site, and Worsening of the skin condition.

Butenafine is available in the form of Cream.

Butenafine is approved in Germany, Japan, Malaysia, India, the U.K., the U.S., and China.

Butenafine belonging to the pharmacological class of Allyl Amine, acts as an antifungal agent.

Although the exact mechanism of action is not fully elucidated, it is hypothesized that butenafine, similar to allylamines, disrupts sterol biosynthesis, particularly ergosterol, by inhibiting squalene monooxygenase, an enzyme responsible for converting squalene to 2,3-oxide squalene. Ergosterol is crucial for the integrity of the fungal cell membrane, and its inhibition results in increased cellular permeability, leading to the leakage of cellular contents. Additionally, the inhibition of squalene monooxygenase leads to the accumulation of squalene, which, when present in high concentrations, is believed to directly contribute to the fungicidal effect by killing fungal cells.

Butenafine has been approved to relieve symptoms and also for the treatment and maintenance of Tinea corporis/tinea cruris, Tinea pedis, Tinea versicolor.

Cmax and Tmax for Butenafine were determined during a study involving healthy subjects. Two groups received different dosages: one group applied 6 grams of the cream to the dorsal skin, while the other applied 20 grams to various areas. After 14 days, the 6-gram group showed a Cmax of 1.4 ± 0.8 ng/mL with a Tmax of 15 ± 8 hours and an AUC0-24 hrs of 23.9 ± 11.3 ng-hr/mL. The 20-gram group showed a Cmax of 5.0 ± 2.0 ng/mL with a Tmax of 6 ± 6 hours and an AUC0-24 hrs of 87.8 ± 45.3 ng-hr/mL. Plasma butenafine HCl concentrations declined in a biphasic pattern with half-lives estimated at 35 hours and >150 hours, respectively.

Butenafine is found to be available in the form of Cream.

Butenafine can be used in the following treatment:

• Tinea corporis/tinea cruris
• Tinea pedis
• Tinea versicolor

Butenafine can help to relieve symptoms and also for the treatment and maintenance of Tinea corporis/tinea cruris, Tinea pedis, Tinea versicolor.

Butenafine is approved for use in the following clinical indications:

• Tinea corporis/tinea cruris
• Tinea pedis
• Tinea versicolor

Tinea infections:

• Tinea corporis/tinea cruris: Apply the 1% Cream topically to the affected and surrounding area(s) once daily until clinical resolution, which usually takes 1 to 3 weeks.
• Tinea pedis (labelled use)/tinea manuum (off-label use): Apply the 1% Cream topically to the affected and surrounding area(s) once or twice daily until 1 week after the clinical resolution, typically for a total of 2 weeks (twice daily) or 4 weeks (once daily).

Butenafine is available in the following dosage forms and strengths:

• Cream: 1%

• Dosage Adjustments in Kidney Patients:

For patients with a creatinine clearance (CrCl) of 50 mL/minute or higher, no dosage adjustment is needed.

For patients with a CrCl between 20 and less than 50 mL/minute, administer 50% of the usual dose.

For patients with a CrCl less than 20 mL/minute, using an alternative agent may be preferred (according to expert opinion) as it has not been adequately studied in this population. If necessary, administer 50% of the usual dose and closely monitor for adverse effects, such as gastrointestinal and hepatic issues.

• Dosage Adjustments in Hepatic Impairment Patients:

Not recommended for use in individuals with chronic or active liver disease.

• Dosage Adjustments in Pediatric Patients:
• For children aged 12 years and adolescents, the dosing should follow the same guidelines as for adults.

Tinea infections:

• Tinea corporis/tinea cruris: Apply the 1% Cream topically to the affected and surrounding area(s) once daily until clinical resolution, which usually takes 1 to 3 weeks.
• Tinea pedis (labelled use)/tinea manuum (off-label use): Apply the 1% Cream topically to the affected and surrounding area(s) once or twice daily until 1 week after the clinical resolution, typically for a total of 2 weeks (twice daily) or 4 weeks (once daily).
• Tinea versicolor: Apply the 1% Cream topically to the affected area(s) and immediate surrounding skin once daily for 2 weeks.

There is no specific food warning related to the use of butenafine. However, it is generally recommended to follow the prescribed instructions for the application of butenafine cream and to avoid ingesting the cream. If any accidental ingestion occurs, seeking medical advice is advised.

The dietary restriction should be individualized as per patient requirements.

Butenafine may be contraindicated under the following conditions:

• Butenafine, 1%, should not be used by individuals who have a known or suspected sensitivity to Butenafine, 1%, or any of its components, as it is contraindicated in such cases.

The treating physician must closely monitor the patient and keep pharmacovigilance as follows:

• Butenafine, 1%, should not be used for ophthalmic, oral, or intravaginal purposes.
• General Precautions: Butenafine, 1%, is intended for external use only. If any irritation or sensitivity occurs during its use, treatment should be stopped, and appropriate therapy should be considered.
• Caution for Infants and Children: To prevent accidental exposure, extra care should be taken while applying Butenafine, 1%, to infants and children below 12 years of age, as this population has not been specifically tested with the cream.
• Caution for Patients Sensitive to Allylamine Antifungals: Physicians should exercise caution when prescribing Butenafine, 1%, to patients known to be sensitive to allylamine antifungals, as cross-reactivity may occur.

It is generally advisable to limit or to avoid alcohol consumption while on Butenafine. Alcohol can strain the liver, and since Butenafine is metabolized in the liver, excessive alcohol consumption might increase the risk of liver damage.

The excretion of butenafine HCl in human milk is not known. Since many drugs are excreted in the human milk, caution should be exercised when prescribing Butenafine, 1%, to nursing women.

Pregnancy:

Pregnancy Category C

Subcutaneous administration of butenafine at doses up to 25 mg/kg/day during organogenesis in rats (equivalent to 0.5 times the maximum recommended human dose for tinea versicolor based on body surface area comparisons) did not result in teratogenic effects.During an oral embryofetal development study conducted on rabbits, no abnormalities were observed in external, visceral, or skeletal structure when given a dose of up to 400 mg butenafine HCl/kg/day during organogenesis. This dose is equivalent to 16 times the maximum recommended human dose for tinea versicolor based on body surface area comparisons. Similarly, in an oral peri- and post-natal developmental

study conducted on rats, there were no harmful effects on postnatal survival, the development of the F1 generation, or their future maturation and fertility when given a dose of up to 125 mg butenafine HCl/kg/day, which is equivalent to 2.5 times the maximum recommended human dose for tinea versicolor based on the body surface area comparisons.

Nevertheless, there are currently no adequate and well-controlled studies conducted in pregnant women with topically applied butenafine. As animal reproduction studies may not always predict human response, this drug should only be used during pregnancy if clearly needed.

There is no specific food warning related to the use of butenafine. However, it is generally recommended to follow the prescribed instructions for the application of butenafine cream and to avoid ingesting the cream. If any accidental ingestion occurs, seeking medical advice is advised.

The adverse reactions related to Butenafine can be categorized as follows:

Common:

• Redness
• Burning
• Stinging
• Irritation
• Itching at the application site
• Worsening of the skin condition

A thorough assessment of potential drug interactions between Butenafine, 1%, and other medications has not been conducted.

The following are the side effects involving Butenafine:

• Redness
• Burning
• Stinging
• Irritation
• Itching at the application site
• Worsening of the skin condition

The use of Butenafine should be prudent in the following group of special populations:

Pregnancy:

Pregnancy Category C

Subcutaneous administration of butenafine at doses up to 25 mg/kg/day during organogenesis in rats (equivalent to 0.5 times the maximum recommended human dose for tinea versicolor based on body surface area comparisons) did not result in teratogenic effects. During an embryofetal development study in rabbits, up to 400 mg of butenafine HCl/kg/day was administered during organogenesis. This dose is equivalent to 16 times the maximum recommended human dose for tinea versicolor based on body surface area comparisons. The study showed no treatment-related external, visceral, or skeletal malformations or variations

. Additionally, in a peri- and post-natal developmental study in rats, up to 125 mg of butenafine HCl/kg/day was administered. This dose is equivalent to 2.5 times the maximum recommended human dose for tinea versicolor based on body surface area comparisons. The study showed no adverse effects on postnatal survival, the development of the F1 generation, or their subsequent maturation and fertility.

Nevertheless, there are currently no adequate and well-controlled studies conducted in pregnant women with topically applied butenafine. As animal reproduction studies may not always predict human response, this drug should only be used during pregnancy if clearly needed.

Lactation:

The excretion of butenafine HCl in human milk is not known. As many drugs are excreted in human milk, caution is to be exercised when prescribing Butenafine, 1%, to nursing women.

Pediatric:

The safety and effectiveness of this medication have not been studied in pediatric patients under the age of 12 years, as tinea versicolor is rare in this age group.

Geriatric Use:

No relevant data has been found.

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Butenafine.

As of now, there have been no reported cases of overdosage of butenafine HCl in humans.

Pharmacodynamics:

Butenafine is a synthetic antifungal agent that belongs to the allylamine class of antifungals. Although the exact mechanism of action is not fully understood, it is believed that butenafine exerts its antifungal effects by modifying cellular membranes, leading to increased membrane permeability and inhibition of fungal growth. Butenafine is particularly effective against dermatophytes and demonstrates superior fungicidal activity compared to other antifungal agents like terbinafine, naftifine, tolnaftate, clotrimazole, and bifonazole. Additionally, it shows good activity against Candida albicans, surpassing the efficacy of terbinafine and naftifine. Butenafine also exhibits low MICs (minimum inhibitory concentrations) against Cryptococcus neoformans and Aspergillus spp.

Pharmacokinetics:

During a study involving healthy individuals, Butenafine was topically applied once daily for 14 days. The participants were divided into two groups: one group applied 6 grams of the cream to the dorsal skin (3,000 cm2) of 7 subjects, while the other group applied 20 grams to the arms, trunk, and groin areas (10,000 cm2) of 12 subjects. After 14 days, the 6-gram group showed a mean peak plasma concentration (Cmax) of 1.4 ± 0.8 ng/mL, with a mean time to peak concentration (Tmax) of 15 ± 8 hours, as well as a mean area under the plasma concentration-time curve (AUC0-24 hrs) of 23.9 ± 11.3 ng-hr/mL. In contrast, the 20-gram group showed a mean Cmax of 5.0 ± 2.0 ng/mL, with a mean Tmax of 6 ± 6 hours and a mean AUC0-24 hrs of 87.8 ± 45.3 ng-hr/mL. The plasma butenafine HCl concentration exhibited a biphasic pattern with estimated half-lives of 35 hours and >150 hours, respectively.

After 72 hours of the last dose application, the mean plasma concentrations is found to be decreased to 0.3 ± 0.2 ng/mL for the 6-gram group and 1.1 ± 0.9 ng/mL for the 20-gram group. However, even 7 days after the last dose application, low levels of butenafine HCl remained in the plasma, with mean concentrations of 0.1 ± 0.2 ng/mL for the 6-gram group and 0.7 ± 0.5 ng/mL for the 20-gram group. The total amount or percentage of butenafine HCl absorbed into the systemic circulation through the skin was not measured. The primary metabolite in urine resulted from hydroxylation at the terminal t-butyl side-chain.

In separate studies conducted on patients with tinea pedis and tinea cruris, butenafine HCl cream, 1%, was applied once daily for 4 weeks and 2 weeks, respectively. Blood samples were collected at different time points post-treatment. The plasma butenafine HCl concentration ranged from undetectable to about 0.3 ng/mL in tinea pedis patients and from undetectable to 2.52 ng/mL in tinea cruris patients. After four weeks of treatment discontinuation, the plasma butenafine HCl concentration ranged from undetectable to around 0.28 ng/mL in tinea cruris patients.

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