Exifine^® (Tablets, Cream, Gel) Instructions for Use

ATC Code

D01BA02 (Terbinafine)

Active Substance

Terbinafine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antifungal drug

Pharmacotherapeutic Group

Antifungal agents used in dermatology; systemic antifungal agents

Pharmacological Action

Terbinafine belongs to the group of allylamines. It has a broad spectrum of antifungal action.

In low concentrations, it has a fungicidal effect on dermatophytes Trichophyton (T. rubrum, T. mentagrophytes, T. tonsurans, T. verrucosum, T. violaceum), Microsporum canis, Epidermophyton floccosum, mold fungi (for example, Aspergillus, Cladosporium, Scopulariopsis brevicaulis), yeast fungi, mainly Candida albicans, and some dimorphic fungi.

Depending on the type of fungus, it has a fungicidal or fungistatic effect on Candida fungi and their mycelial forms.

Terbinafine disrupts the early stage of the biosynthesis of the main component of the fungal cell membrane, ergosterol, by inhibiting the enzyme squalene epoxidase.

Squalene epoxidase is not associated with the cytochrome P450 system (CYP450), therefore Terbinafine does not affect the metabolism of hormones and drugs whose metabolism is associated with CYP450.

When taken orally, it accumulates in the skin, nails, and hair in an amount that has a fungicidal effect.

Systemic treatment of tinea versicolor caused by Malassezia furfur is ineffective.

Pharmacokinetics

When taken orally, it is well absorbed; half of the taken dose is absorbed in 0.8 hours; half of the taken dose is distributed in the body in 4.6 hours.

After 1-2 hours after oral administration of a single 250 mg dose, the C_max of the drug in blood plasma reaches 0.97 µg/ml.

Bioavailability is 80%.

Food intake does not affect the bioavailability of terbinafine.

Terbinafine is intensively bound to plasma proteins (99%), quickly spreads in tissues, penetrates into the dermal layer of the skin and nail plates.

It penetrates into the secretion of the sebaceous glands and accumulates in high concentrations in the hair follicles, hair, skin, and subcutaneous tissue.

Already after a few weeks of treatment, it accumulates in the nails in concentrations that provide a fungicidal effect.

T_1/2 is 16-18 hours.

T_1/2 of the terminal phase is 200-400 hours.

It is biotransformed in the liver to inactive metabolites: 80% of the taken dose is excreted in the urine in the form of metabolites, the rest (20%) with feces.

Does not accumulate in the body.

The age of patients does not affect the pharmacokinetics of terbinafine, but elimination may decrease in case of kidney or liver damage, leading to high concentrations of terbinafine in the blood.

It is excreted in breast milk.

Indications

• Mycoses of the scalp (trichophytosis, microsporosis);
• Mycoses of the skin and nails caused by Trichophyton (T. rubrum, T. mentagrophytes, T. verrucosum, T. violaceum), Microsporum (M. canis, M. gypseum) and Epidermophyton floccosum;
• Onychomycosis;
• Severe, widespread dermatomycoses of the smooth skin of the trunk and extremities requiring systemic treatment;
• Candidiasis of the skin and mucous membranes.

ICD codes

Dosage Regimen

Gel

Apply externally 1-2 times/day.

Adults and children 12 years and older: Before applying the cream, it is necessary to clean and dry the affected areas.

The cream is applied 1 or 2 times a day 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 areas where the cream is applied can be covered with gauze, especially at night.

Duration of treatment and frequency of drug application

Dermatomycosis of smooth skin and inguinal dermatomycosis (including dermatomycosis of the trunk, dermatomycosis of the shins): 1 week 2 times a day (morning and evening).

Dermatomycosis of the feet 1 week 2 times a day between the toes (morning and evening), 2 weeks 1 time a day (top and sides of the foot).

Fungal skin infections caused by yeast (skin candidiasis) 1 week 1 time a day.

Tinea versicolor 2 weeks 1 time a day.

If after 1-2 weeks of treatment there are no signs of improvement, the diagnosis should be verified.

Elderly patients (over 65 years)

No dose adjustment is required in the elderly.

Cream

For external use. Before applying Exifine^® preparation, it is necessary to clean and dry the affected areas.

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 areas where the cream is applied can be covered with gauze, especially at night.

Average duration and frequency of application

Dermatomycosis of the trunk, shins – 1 week 1 time/day;

Tinea cruris – 1-2 weeks 1 time per week.

Dermatomycosis of the feet – 1 week 1 time per day.

Skin candidiasis – 1-2 weeks 1 or 2 times/day.

Tinea versicolor – 2 weeks 1 or 2 times/day.

The duration of the treatment depends on the indication and the severity of the disease.

A decrease in the severity of clinical manifestations is noted in the first days of treatment.

For the prevention of recurrences of foot mycoses – 2-3 courses of 2 weeks each with a break of 7 days.

The dosing regimen of Exifine^® in elderly persons does not differ from that described above.

Tablets

The duration of the treatment course and the dosing regimen are set individually and depend on the localization of the process and the severity of the disease.

Onychomycosis

Usual dose: 250 mg once/day.

Duration of therapy is about 6-12 weeks.

For damage to the nails of the fingers and toes (except for the big toe), or in young patients, the duration of treatment may be less than 12 weeks.

For infection of the big toe, a 3-month course of treatment is usually sufficient.

In rare cases, with a slow rate of nail growth, longer treatment up to 6 or more months may be required.

Fungal skin infections.

Duration of treatment for interdigital, plantar or ‘sock-type’ localization of infection is 2-6 weeks, for mycoses of other body areas: shins – 2-4 weeks, trunk – 4 weeks, for mycoses caused by Candida – 2-4 weeks; for mycoses of the head caused by Microsporum canis – more than 4 weeks.

Children are usually prescribed 125 mg (1/2 tablet).

The duration of treatment for mycoses of the scalp is about 4 weeks, and may be longer when infected with Microsporum canis.

For body weight less than 20 kg – 62.5 mg (1/4 tablet) once/day, for body weight from 20 to 40 kg – 125 mg (1/2 tablet) once/day, for body weight more than 40 kg – 250 mg (1 tablet) once/day.

Elderly patients are prescribed the drug in the same doses as adults.

For severe impairment of liver and/or kidney function (creatinine clearance 50 ml/min or blood creatinine concentration more than 300 µmol/l) – 125 mg once/day.

Adverse Reactions

Adverse effects are usually of moderate and mild severity and are temporary.

From the digestive system often – feeling of a full stomach, dyspepsia, nausea, loss of appetite, abdominal pain, diarrhea; infrequently – taste disturbance, including loss, which recovers a few weeks after cessation of treatment; rarely – cholestasis, jaundice, hepatitis, asymptomatic increase in the level of liver transaminases.

Despite the unproven causal relationship of these disorders with the intake of terbinafine, in case of development of hepatobiliary dysfunction, treatment with Exifine^® should be discontinued.

From the CNS rarely – paresthesia, hypesthesia, dizziness; very rarely – depression, feeling of increased anxiety.

From the musculoskeletal system often – arthralgia, myalgia.

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

From the immune system often – urticaria, multiforme erythema, rarely systemic allergic reactions (serum sickness-like reactions, angioneurotic edema); very rarely – severe skin reactions (toxic epidermal necrolysis, Stevens-Johnson syndrome, photosensitivity).

If skin rashes progress, treatment with terbinafine should be discontinued.

Other often – headache, malaise, feeling of tiredness; very rarely – exacerbation of psoriasis, increased hair loss.

Contraindications

• Children under 2 years of age, because there is not enough data on the use of the drug in children with body weight less than 12 kg;
• Pregnancy;
• Breastfeeding period;
• Hypersensitivity to the components of the drug.

With caution hepatic and/or renal insufficiency; alcoholism; blood diseases; tumors; metabolic diseases; pathology of the vessels of the extremities, psoriasis.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

With caution.

For severe impairment of liver function – 125 mg once/day.

Use in Renal Impairment

With caution.

For severe impairment of kidney function (creatinine clearance 50 ml/min or blood creatinine concentration more than 300 µmol/l) – 125 mg once/day.

Pediatric Use

Contraindicated

• Children under 2 years of age, because there is not enough data on the use of the drug in children with body weight less than 12 kg.

Children are usually prescribed 125 mg (1/2 tablet).

The duration of treatment for mycoses of the scalp is about 4 weeks, and may be longer when infected with Microsporum canis.

For body weight less than 20 kg – 62.5 mg (1/4 tablet) once/day, for body weight from 20 to 40 kg – 125 mg (1/2 tablet) once/day, for body weight more than 40 kg – 250 mg (1 tablet) once/day.

Geriatric Use

Elderly patients are prescribed the drug in the same doses as adults.

Special Precautions

Irregular use of terbinafine or premature discontinuation of treatment leads to a recurrence of the disease.

The duration of therapy can also be influenced by factors such as the presence of concomitant diseases, the condition of the nails at the beginning of the treatment course.

If after 2 weeks of treatment of a skin infection there is no improvement in the condition, it is necessary to re-determine the causative agent of the disease and its sensitivity to the drug.

Systemic use for onychomycosis is justified only in case of total damage to most nails, the presence of severe subungual hyperkeratosis, and ineffectiveness of previous local therapy.

When treating onychomycosis, a clinical response is usually observed several months after mycological cure and the end of the treatment course, which is due to the rate of regrowth of a healthy nail.

Removal of nail plates during the treatment of onychomycosis of the hands for 3 weeks and onychomycosis of the feet for 6 weeks is not required.

In the presence of severe renal failure (creatinine clearance less than 50 ml/min or creatinine in the blood more than 300 µmol/l), in case of impaired liver function, the dose of terbinafine should be halved.

In the presence of liver disease, the clearance of terbinafine may be reduced.

In case of reduced liver function, half the adult dose is prescribed.

During treatment, it is necessary to monitor the level of liver transaminases in the blood serum.

In rare cases, after 3 months of treatment, cholestasis and hepatitis occur.

If signs of impaired liver function appear (weakness, persistent nausea, loss of appetite, abdominal pain, jaundice, dark urine or colorless stools), the drug should be discontinued.

Prescribing terbinafine to patients with psoriasis requires increased caution, because in very rare cases Terbinafine can provoke an outbreak of psoriasis.

When treating with terbinafine, general hygiene rules should be observed to prevent the possibility of re-infection through linen and shoes.

During treatment (every 2 weeks) and at the end of it, it is necessary to carry out antifungal treatment of shoes, socks and stockings.

Influence on the ability to drive vehicles and mechanisms

Terbinafine does not affect the ability to drive a car and perform work that requires increased concentration.

Overdose

Symptoms nausea, vomiting, pain in the lower abdomen, in the epigastric region.

Treatment gastric lavage followed by the administration of activated charcoal and/or symptomatic therapy

Drug Interactions

Practically does not affect the clearance of drugs metabolized with the participation of cytochrome P450 (for example, cyclosporine, terfenadine, tolbutamide, triazolam, oral contraceptives).

Inhibits CYP2D6 and prevents the metabolism of drugs such as tricyclic antidepressants and selective serotonin reuptake blockers (desipramine, fluvoxamine), beta-blockers (metoprolol, propranolol), antiarrhythmic drugs (flecainide, propafenone), MAO-B inhibitors (selegiline) and antipsychotics (chlorpromazine, haloperidol).

Drugs – inducers of CYP450 enzymes (for example, rifampicin) can accelerate the excretion of terbinafine from the body.

Drugs – inhibitors of CYP450 (for example, cimetidine) can slow down the metabolism and excretion of terbinafine from the body.

When using these drugs simultaneously, adjustment of the terbinafine dose may be required.

Violation of the menstrual cycle is possible with the simultaneous use of terbinafine and oral contraceptives.

Reduces the clearance of caffeine by 21% and prolongs its half-life by 31%.

Does not affect the clearance of antipyrine, digoxin, warfarin.

Ethanol and other hepatotoxic drugs increase the risk of developing a hepatotoxic effect.

Storage Conditions

Store in a dry place protected from light, out of reach of children, at a temperature up to 25°C (77°F).

Shelf Life

Shelf life – 3 years.

Dispensing Status

The drug is dispensed by prescription.

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.