Terbisil^® (Tablets, Cream) Instructions for Use

ATC Code

D01BA02 (Terbinafine)

Active Substance

Terbinafine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antifungal drug

Pharmacotherapeutic Group

Antifungal agent

Pharmacological Action

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

In low concentrations, it exerts a fungicidal effect on dermatophytes Trichophyton spp. (Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Trichophyton verrucosum, Trichophyton violaceum), Microsporum canis, Epidermophyton floccosum, and mold fungi (for example, Scopulariopsis brevicaulis).

On yeast fungi, mainly Candida albicans, and their mycelial forms, it exerts, depending on the fungal species, a fungicidal or fungistatic effect.

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

When used orally, it is not effective in the treatment of tinea versicolor caused by Pityrosporum ovale, Pityrosporum orbiculare, Malassezia furfur.

Pharmacokinetics

Absorption

When taken orally, it is well absorbed, with absorption exceeding 70%; the absolute bioavailability of terbinafine due to the first-pass effect is approximately 50%.

After a single oral dose of 250 mg, its C_max in plasma is reached within 1.5 hours and is 1.3 µg/ml.

AUC is 4.56 µg×h/ml; when taken simultaneously with food, AUC increases by 20%.

With long-term use, C_max increases by 25%, and AUC increases by 2.3 times.

Distribution

Plasma protein binding is 99%.

It is rapidly distributed in tissues, penetrates the dermal layer of the skin and nail plates.

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

Metabolism and Excretion

It undergoes significant metabolism; the resulting metabolites do not possess antifungal activity.

Renal excretion accounts for 70%.

The effective T_1/2 is 30 hours, the terminal T_1/2 is 200-400 hours (indicating prolonged excretion from the skin and adipose tissue).

It does not accumulate in the body.

Pharmacokinetics in Special Clinical Cases

The C_ss of terbinafine does not depend on age.

The age of patients does not affect the pharmacokinetics of terbinafine; however, elimination may decrease in cases of liver and kidney damage, leading to high concentrations of terbinafine in the blood.

The concentration of terbinafine in plasma does not depend on gender.

Indications

• Mycoses of the scalp (tinea capitis);
• Fungal diseases of the skin and nails (onychomycosis) caused by Trichophyton spp. (T. rubrum, T. mentagrophytes, T. verrucosum, T. violaceum), Microsporum spp. (M. canis, M. gypseum) and Epidermophyton floccosum;
• 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

Cream

For external use.

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.

Adults and children 12 years and older

Average duration of treatment and frequency of drug application

Dermatomycosis of the trunk, legs, inguinal dermatomycosis: 1 week, once daily.

Dermatomycosis of the feet 1 week, once daily.

Skin candidiasis 1-2 weeks, once or twice daily.

Tinea versicolor 2 weeks, once or twice daily.

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

In case of irregular treatment or premature discontinuation, there is a risk of recurrence of the infection.

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

In elderly patients, the dosage regimen of Terbisil^® cream does not differ from that described above.

The dosage regimen for children and adolescents from 12 to 18 years does not differ from the dosage regimen for adults.
Safety and efficacy in children under 12 years of age have not been established (see section “Contraindications”).

Tablets

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

The drug is taken orally, after meals.

Adults

The usual dose is 250 mg once daily.

Onychomycosis the duration of therapy is on average 6-12 weeks.

For involvement of fingernails and toenails (excluding the big toe), or in younger 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.

Some patients with reduced nail growth rate may require a longer treatment period.

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: legs – 2-4 weeks, trunk – 2-4 weeks; for mycoses caused by fungi of the genus Candida – 2-4 weeks; for mycoses of the scalp caused by fungi of the genus Microsporum – more than 4 weeks.

Children

Usually prescribed 125 mg.

For body weight from 20 to 40 kg– 125 mg once daily.

For body weight over 40 kg – 250 mg once daily.

The duration of treatment for scalp mycoses is about 4 weeks; for infection with Microsporum canis – treatment may be longer.

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

Patients with hepatic and renal impairment Terbisil^® is prescribed at a dose of 125 mg once daily.

Adverse Reactions

From the digestive system: frequently – feeling of stomach fullness, nausea, abdominal pain, diarrhea, decreased appetite; in isolated cases (0.1-1%) – taste disturbances, including loss of taste (recovery occurs within several weeks after discontinuation of treatment); rarely (0.01-0.1%) – hepatotoxic effect (increased activity of liver enzymes, liver failure).

From the CNS frequently – headache, dizziness.

From the hematopoietic system very rarely (<0.01%) – neutropenia, agranulocytosis, thrombocytopenia.

From the immune system rarely – anaphylactoid reactions, including angioedema, exacerbation of systemic lupus erythematosus.

From the skin and subcutaneous tissue frequently – rash, urticaria; very rarely – psoriasis-like skin rashes, exacerbation of psoriasis, Stevens-Johnson syndrome, toxic epidermal necrolysis, hair loss, acute generalized exanthematous pustulosis.

From the musculoskeletal system frequently – arthralgia, myalgia.

General reactions very rarely – fatigue.

Contraindications

• Acute or chronic liver diseases;
• Children under 2 years of age (efficacy and safety have not been established);
• Lactation period;
• Hypersensitivity to the active substance or to any excipient.

With caution pregnancy; renal failure; alcoholism; bone marrow depression; tumors; metabolic diseases; occlusive vascular diseases of the extremities.

Use in Pregnancy and Lactation

There are no data on the safety of terbinafine use during pregnancy. Therefore, Terbinafine should be used during pregnancy only if the intended benefit to the mother outweighs the potential risk to the fetus.

Terbinafine is excreted in breast milk. Its use during breastfeeding is contraindicated.

Use in Hepatic Impairment

Contraindicated in acute or chronic liver diseases.

Use in Renal Impairment

The drug should be prescribed with caution in renal failure.

Pediatric Use

The drug is contraindicated in children under 2 years of age (efficacy and safety have not been established).

Geriatric Use

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

Special Precautions

Unlike Terbisil^® cream, the tablets are not effective against tinea versicolor caused by the pathogen Malassezia furfur.

Irregular use of Terbisil^® or premature discontinuation of treatment may lead to 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 for onychomycosis.

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

Systemic use for onychomycosis is justified only in cases of total involvement of most nails, the presence of pronounced subungual hyperkeratosis, and ineffectiveness of previous local therapy.

In the treatment of onychomycosis, a clinical response, confirmed by laboratory tests, 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 liver disease, the clearance of terbinafine may be reduced.

During treatment, it is necessary to monitor the indicators of liver enzyme activity in the blood serum.

In rare cases, after 3 months of treatment, cholestasis and hepatitis may occur. If signs of impaired liver function appear (weakness, persistent nausea, loss of appetite, excessive abdominal pain, jaundice, dark urine, or discolored stools), the drug should be discontinued.

In severe renal impairment (creatinine clearance <50 ml/min or blood creatinine >300 µmol/l) and impaired liver function, the dose of Terbisil^® should be reduced by half.

Prescribing Terbisil^® to patients with psoriasis requires caution, as in very rare cases the drug may provoke an exacerbation of psoriasis.

During treatment with Terbisil^®, general hygiene rules should be observed to prevent the possibility of reinfection through underwear and shoes. During treatment (after 2 weeks) and at the end of it, antifungal treatment of shoes, socks, and stockings should be carried out.

Effect on ability to drive vehicles and mechanisms

There are no data indicating the effect of Terbisil^® on the ability to drive a car and perform work requiring increased concentration.

Overdose

Symptoms nausea, vomiting, headache, dizziness, pain in the epigastric region and lower abdomen, frequent urination.

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

Drug Interactions

It inhibits the isoenzyme CYP2D6 and impairs the metabolism of drugs such as tricyclic antidepressants and selective serotonin reuptake inhibitors (e.g., desipramine, fluvoxamine), beta-blockers (metoprolol, propranolol), antiarrhythmic drugs (flecainide, propafenone), MAO-B inhibitors (e.g., selegiline) and antipsychotic drugs (e.g., chlorpromazine, haloperidol).

Drugs that are inducers of cytochrome P450 isoenzymes (e.g., rifampicin) may accelerate the metabolism and excretion of terbinafine from the body.

Drugs that are inhibitors of cytochrome P450 isoenzymes (e.g., cimetidine) may slow down the metabolism and excretion of terbinafine from the body.

When these drugs are used concomitantly, dose adjustment of terbinafine may be required.

Menstrual cycle disturbances are possible with the simultaneous use of terbinafine and oral contraceptives.

Terbinafine reduces the clearance of caffeine by 19% and prolongs its T_1/2 by 31%.

It does not affect the clearance of phenazone, digoxin, warfarin.

When used concomitantly with ethanol or drugs that have a hepatotoxic effect, there is a risk of drug-induced liver damage.

Storage Conditions

The drug should be stored out of the reach of children, protected from light, at a temperature from 15°C (59°F) to 30°C (86°F).

Shelf Life

Shelf life – 5 years. Do not use after the expiration date printed on the packaging.

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.