Binafin (Tablets, Cream) Instructions for Use

ATC Code

D01AE15 (Terbinafine)

Active Substance

Terbinafine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

External antifungal drug

Pharmacotherapeutic Group

Antifungal agent

Pharmacological Action

An antifungal drug, which is an allylamine. It has a broad spectrum of action.

Active against fungi causing diseases of the skin, hair, and nails: Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Trichophyton verrucosum, Trichophyton violaceum, Microsporum canis, Epidermophyton floccosum, as well as yeast-like fungi of the genus Candida (including Candida albicans) and Pityrosporum.

At low concentrations, it has a fungicidal effect against dermatophytes, molds, and some dimorphic fungi. The effect on yeast-like fungi can be fungicidal or fungistatic, depending on the type of fungus.

Terbinafine specifically inhibits an early stage of sterol biosynthesis in the fungal cell. This leads to ergosterol deficiency and intracellular accumulation of squalene, which causes the death of the fungal cell. The action of terbinafine is carried out by inhibiting the enzyme squalene epoxidase in the fungal cell membrane. This enzyme is not related to the cytochrome P450 system. Terbinafine does not affect the metabolism of hormones or other drugs.

Pharmacokinetics

Absorption

After a single oral dose of 250 mg of terbinafine, C_max in plasma is reached after 2 hours and is 0.97 µg/ml. The half-absorption period is 0.8 hours. Food intake does not affect the bioavailability of terbinafine.

When the cream is applied topically, less than 5% of the dose is absorbed, thus the systemic exposure to the drug is minimal.

Distribution

Binding to plasma proteins is 99%. The half-distribution period is 4.6 hours. It quickly penetrates into the dermal layer of the skin and accumulates in the lipophilic stratum corneum. Terbinafine also penetrates into the secretion of the sebaceous glands, which within the first few weeks leads to the creation of high fungicidal concentrations in the hair follicles, nails, and in the skin rich in sebaceous glands.

Metabolism

Terbinafine is rapidly biotransformed in the liver with the active participation of isoenzymes CYP2C9, CYP1A2, CYP3A4, CYP2C8, CYP2C19 with the formation of inactive metabolites.

Excretion

Terbinafine is excreted in breast milk. It is excreted mainly in the urine as metabolites. T_1/2 is 17 hours. There is no evidence of drug accumulation in the body.

Pharmacokinetics in special clinical cases

No changes in C_ss of terbinafine depending on age were detected.

In patients with impaired liver or kidney function, the elimination rate of the drug may be slowed down, leading to higher plasma concentrations of terbinafine. In pharmacokinetic studies after a single dose of Binafin in patients with concomitant liver diseases, a possible decrease in terbinafine clearance by 50% was shown.

Indications

For tablets

• onychomycosis caused by dermatophyte fungi;
• Mycoses of the scalp;
• Mycoses of the skin of the trunk, shins, feet caused by dermatophytes and yeast-like fungi of the genus Candida in cases where the localization, severity and prevalence of the infection justify the appropriateness of oral therapy.

For cream

• Fungal infections of the skin caused by dermatophytes such as Trichophyton (including Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton verrucosum, Trichophyton violaceum, Trichophyton interdigitalis, Trichophyton tonsurans, Trichophyton gypseum), Microsporum canis and Epidermophyton floccosum;
• Yeast infections of the skin, mainly caused by Candida spp. (including Candida albicans);
• pityriasis versicolor, caused by Pityrosporum orbiculare (also known as Malassezia furfur).

Unlike Binafin in the form of a cream, the use of tablets for the treatment of pityriasis versicolor is ineffective.

ICD codes

Dosage Regimen

Cream

Children over 2 years of age are prescribed the drug in tablet form once a day. The single dose depends on the child’s body weight. The duration of therapy depends on the indications and severity of the disease.

Adults are prescribed the drug in tablet form at a dose of 250 mg once a day. The duration of therapy depends on the indications and severity of the disease.

*Complete disappearance of the manifestations of the infection and complaints associated with it may occur only a few weeks after mycological cure.

In onychomycosis, patients with a reduced nail growth rate may require longer treatment. The optimal clinical effect is observed several months after mycological cure and cessation of therapy. This is determined by the period of time required for the regrowth of a healthy nail.

For patients with impaired renal function (CrCl <50 ml/min or serum creatinine concentration greater than 300 µmol/l), the dose of the drug should be halved.

Since prospective clinical studies on the course use of Binafin in patients with concomitant chronic or active liver diseases have not been conducted, its prescription to this group of patients is not recommended.

Adults and children over 12 years of age are prescribed the drug in the form of a cream 1-2 times a day. Before applying the cream, it is necessary to clean and dry the affected areas of the skin. The cream is applied in a thin layer to the affected skin and adjacent areas and rubbed in gently. For infections accompanied by intertrigo (under the breasts, in the interdigital spaces, between the buttocks, in the groin area), the cream can be applied under a bandage, especially at night.

The average duration and frequency of cream application depend on the type of mycosis

A decrease in the severity of clinical manifestations is usually noted in the first days of treatment. In case of irregular use or premature discontinuation of treatment, there is a risk of disease recurrence. If no signs of improvement are noted after 2 weeks of treatment, the diagnosis should be verified.

For elderly patients, the drug is prescribed in the same doses as for adults, but when prescribing tablets, the presence of concomitant impaired liver or kidney function in patients of this age group should be taken into account.

Tablets

Children over 2 years of age are prescribed the drug in tablet form once a day. The single dose depends on the child’s body weight.

Adults are prescribed the drug in tablet form at a dose of 250 mg once a day. The duration of therapy depends on the indications and severity of the disease.

In onychomycosis, patients with a reduced nail growth rate may require longer treatment. The optimal clinical effect is observed several months after mycological cure and cessation of therapy. This is determined by the period of time required for the regrowth of a healthy nail.

Patients with impaired renal function (CrCl less than 50 ml/min or serum creatinine concentration greater than 300 µmol/l) should have the dose of the drug halved.

Since clinical studies on the course use of Binafin in patients with concomitant impaired liver function have not been conducted, its prescription to this group of patients is not recommended.

Adults and children over 12 years of age are prescribed the drug in the form of a cream 1-2 times a day. Before applying the cream, it is necessary to clean and dry the affected areas of the skin. The cream is applied in a thin layer to the affected skin and adjacent areas and rubbed in gently. For infections accompanied by intertrigo (under the breasts, in the interdigital spaces, between the buttocks, in the groin area), the cream can be applied under a bandage, especially at night.

The average duration and frequency of cream application depend on the type of mycosis

A decrease in the severity of clinical manifestations is usually noted in the first days of treatment. In case of irregular use or premature discontinuation of treatment, there is a risk of disease recurrence. If no signs of improvement are noted after 2 weeks of treatment, the diagnosis should be verified.

For elderly patients, the drug is prescribed in the same doses as for adults, but when prescribing tablets, the presence of concomitant impaired liver or kidney function in patients of this age group should be taken into account.

Adverse Reactions

From the digestive system frequently (1-10%) – dyspepsia, mild abdominal pain, feeling of stomach fullness, nausea, loss of appetite, diarrhea; sometimes (0.1-1%) – taste disturbance, including loss of taste (recovers a few weeks after cessation of treatment); rarely (0.01-0.1%) – hepatobiliary disorders, primarily associated with cholestasis. There are reports of cases of liver failure, some of which were fatal or required liver transplantation, however, in most cases, the patients had serious concomitant diseases and their connection with the use of Binafin was considered doubtful.

From the musculoskeletal system frequently (1-10%) – myalgia, arthralgia.

From the hematopoietic system very rarely – neutropenia, agranulocytosis, thrombocytopenia.

Local reactions rarely – hyperemia, sensation of itching or burning at the site of cream application, which rarely lead to the need to discontinue therapy.

Allergic reactions frequently (1-10%) – skin rash, urticaria; very rarely (<0.01%) – toxic epidermal necrolysis, Stevens-Johnson syndrome, anaphylactoid reactions. If a progressive skin rash develops, treatment with Binafin should be discontinued.

Other very rarely – alopecia (a causal relationship with the use of the drug has not been established).

Binafin is generally well tolerated. Side effects observed when taking Binafin are usually mild or moderate and are transient.

Contraindications

• Hypersensitivity to terbinafine or any other component of the drug.

Use in Pregnancy and Lactation

Use of the drug during pregnancy is possible only if the intended benefit to the mother outweighs the potential risk to the fetus.

Terbinafine is excreted in breast milk, therefore, if it is necessary to use the drug during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

Since clinical studies on the course use of Binafin in patients with concomitant impaired liver function have not been conducted, its prescription to this group of patients is not recommended.

Use in Renal Impairment

Patients with impaired renal function (CrCl <50 ml/min or serum creatinine concentration greater than 300 µmol/l) should have the dose of the drug halved.

Pediatric Use

Data on the use of Binafin tablets in children under 2 years of age (whose body weight is less than 12 kg) are not available. In children over 2 years of age, the tolerability of oral Binafin is good.

The use of Binafin cream in children under 12 years of age is not recommended.

Special Precautions

If during treatment with Binafin the patient develops symptoms of impaired liver function (weakness, nausea, lack of appetite, vomiting, jaundice, pain in the right hypochondrium, darkening of urine or lightening of stool), laboratory confirmation of impaired liver function (determination of ALT, AST levels) should be carried out and the drug should be discontinued. The patient should be warned about the need to consult a doctor if such symptoms appear.

Constant monitoring is necessary for patients receiving treatment with drugs that are predominantly metabolized with the participation of the isoenzyme CYP2D6 (including tricyclic antidepressants, beta-blockers, selective serotonin reuptake inhibitors and MAO-B inhibitors) simultaneously with Binafin, especially in cases where the concomitantly used drug has a narrow therapeutic range.

Terbinafine in the form of a cream is intended for external use only. Avoid getting the cream on the mucous membrane of the eyes.

Use in pediatrics

Data on the use of Binafin tablets in children under 2 years of age (whose body weight is less than 12 kg) are not available. In children over 2 years of age, the tolerability of oral Binafin is good.

The use of Binafin cream in children under 12 years of age is not recommended.

Effect on ability to drive vehicles and machinery

Data on the effect of Binafin on the ability to drive a car and work with machinery are not available.

Overdose

There are reports of several cases of Binafin overdose (the dose taken was up to 5 g).

Symptoms headache, nausea, pain in the epigastric region, dizziness.

Treatment gastric lavage followed by the use of activated charcoal. If necessary, symptomatic therapy is carried out.

There are no data on terbinafine overdose with topical application. However, if the drug is accidentally ingested, the same side effects as with an overdose of tablets can be expected.

Drug Interactions

Results of studies conducted in healthy volunteers show that Binafin has a slight ability to reduce or increase the clearance of drugs that are metabolized with the participation of the cytochrome P450 system (including cycloserine, tolbutamide, triazolam, oral contraceptives).

In vitro studies have revealed that Terbinafine inhibits CYP2D6-mediated metabolism. This may be clinically significant when co-administered with drugs that are metabolized by this enzyme; such as tricyclic antidepressants, beta-blockers, selective serotonin reuptake inhibitors and MAO-B inhibitors (especially in cases where the concomitantly used drug has a narrow therapeutic range).

In women simultaneously taking Binafin and oral contraceptives, in some cases, irregularity of the menstrual cycle was noted, although the frequency of these disorders remains within the limits observed in patients using only oral contraceptives.

The total clearance of terbinafine may be accelerated by drugs that accelerate metabolism (rifampicin) and may be slowed down by drugs that inhibit cytochrome P450 (cimetidine). If it is necessary to use these drugs simultaneously, adequate dose adjustment may be required.

Drug interactions of Binafin in the form of a cream have not been described.

Storage Conditions

Tablets should be stored in a dry place at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 3 years.

The cream should be stored out of the reach of children at a temperature from 2°C (35.6°F) to 30°C (86°F). The shelf life is 3 years.

Dispensing Status

The drug in tablet form is dispensed by prescription.

The drug in cream form is approved for use as an over-the-counter product.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.