Terbinafin

General characteristics. Structure:

Active ingredient: 0,25 g of a terbinafin a hydrochloride in terms of тербинафин.

Excipients: cellulose microcrystallic — 0,08 g, a hypro rod (hydroxypropyl cellulose) — 0,025g, croscarmellose sodium — 0,025 g, silicon dioxide colloid — 0,01 g, calcium stearate — 0,005 g, lactoses monohydrate — before receiving a tablet weighing 0,5 g.

Antifungal drug with pronounced fungicidal action.

Pharmacological properties:

Pharmacodynamics. Terbinafin represents allylamine which possesses a broad spectrum of activity concerning the mushrooms causing diseases of skin, a hair and nails, including dermatophytes. In low concentration has fungicidal effect on Trychophyton spp dermatophytes. (T. rubrum, T. mentagrophytes, T. verrucosum, T. tonsurans, T. violaceum), Microsporum canis, Epidermophyton floccosum, mold mushrooms (for example, Aspergillus, Cladosporium, Scopulariopsis brevicaulis), barmy mushrooms, mainly Candida albicans. In low concentration тербинафин has fungicidal effect concerning dermatophytes, mold and some dimorphous mushrooms. Activity concerning barmy mushrooms, depending on their look, can be fungicidal or fungistatic.

Terbinafin specifically suppresses an early stage of biosynthesis of sterols in a mushroom cell. It leads to deficit of ergosterol and to intracellular accumulation of squalene that causes death of a cell of a mushroom. Action of a terbinafin is carried out by skvalenepoksidaza enzyme inhibition in a cellular membrane of a mushroom. This enzyme does not belong to system of P450 cytochrome. Terbinafin does not exert impact on metabolism of hormones or other medicines.

At Terbinafin's reception inside in skin, hair and nails the concentration of drug providing fungicidal action are created.

At oral administration it is not effective at treatment multi-colored depriving, the caused Pityrosporum ovale, Pityrosporum orbiculare (Malassezia furfur).

Pharmacokinetics. After a single dose of a terbinafin inside in a dose of 250 mg its maximum concentration in plasma is reached in 2 hours and makes (Cmax) - 0,97 mkg/ml. The period of semi-absorption makes 0,8 hours, the semi-distribution period — 4,6 hours. Communication with proteins of a blood plasma - 99%. At a concomitant use with food dose adjustment of drug is not required.

Terbinafin quickly gets through skin and collects in sebaceous glands. High concentration are created in hair follicles and hair, in several weeks of use gets into nail plates. Collects in a corneous layer of skin (concentration increases by 10 times for the 2nd day after reception of 250 mg, by 70 times — for the 12th day) and nails (speed of diffusion exceeds nail growth rate) in the concentration providing fungicidal action.

Terbinafin is metabolized in a liver with formation of inactive metabolites. The elimination half-life makes 16-18 hours. An elimination half-life of a terminal phase — 200-400 hours. It is removed generally by kidneys (70%) in the form of metabolites, and also through skin. Any proofs of cumulation of drug in an organism are not available. It is allocated with breast milk. Changes of equilibrium concentration of a terbinafin in plasma depending on age are not revealed, but patients with a renal failure or a liver can have a slowed-down drug removal speed that results in higher concentration of a terbinafin in blood.

Indications to use:

- the fungus diseases of skin and nails (onychomycoses) caused by Trychophyton spp. (T. rubrum, T. mentagrophytes, T. verrucosum, T. tonsurans, T. violacium), Microsporum spp. (M. canis, M. gypseum) and Epidermophyton floccosum;
- mycoses of a pilar part of the head (trichophytosis, microsporia);
- the heavy, widespread dermatomycoses of smooth skin of a trunk and extremities demanding system treatment;
- candidiases of skin and mucous membranes.

Route of administration and doses:

Adult: Inside, after food. Usual dose: 250 mg of 1 times a day.

To children is more senior than 3 years: at body weight from 20 to 40 kg — 125 mg of 1 times a day; At body weight more than 40 kg — 250 mg of 1 times a day.

Duration of a course of treatment and the mode of dosing are established in an individual order and depend on localization of process and disease severity.

Onychomycosis: therapy duration on average 6-12 weeks. At damage of nails of fingers of brushes and feet (except for a foot thumb), or at young age of the patient duration of treatment can be less than 12 weeks. At an infection of a thumb of foot of usually rather 3-month course of treatment.

Longer term of treatment can be required by some patients at whom the growth rate of nails is reduced.

Fungal infections of skin: treatment duration at interdigital, bottom or as "socks" of localization of an infection makes 2-6 weeks; at mycoses of other body parts: shins — 2-4 weeks, trunks — 2-4 weeks; at the mycoses caused by sort Candida mushrooms — 2-4 weeks; at the mycoses of a pilar part of the head caused by sort Microsporum mushrooms — more than 4 weeks.

Duration of treatment of mycoses of a pilar part of the head makes about 4 weeks, at Microsporum canis infection — can be longer.

The elderly patient drug is appointed in the same doses, as the adult. To patients with a liver or renal failure — 125 mg once a day.

Features of use:

Irregular use or the early end of treatment increases risk of development of a recurrence.
Such factors as existence of associated diseases, condition of nails at onychomycoses at the beginning of a course of treatment also can influence duration of therapy.

If in 2 weeks of treatment of a skin infection improvement of a state is not noted, it is necessary to define repeatedly an infestant and its sensitivity to drug. 

System use at an onychomycosis is justified only in case of total defeat of the majority of nails, existence of the expressed hyponychial hyperkeratosis, inefficiency of the previous local therapy.

At treatment of an onychomycosis the clinical answer confirmed laboratory is usually observed in several months after mycologic treatment and the termination of a course of treatment that is caused by the speed of growth of a healthy nail. 

Removal of nail plates at treatment of an onychomycosis of brushes within 3 weeks and an onychomycosis of feet within 6 weeks is not required.

In the presence of a liver disease the clearance of a terbinafin can be reduced.

During treatment it is necessary to carry out control of indicators of activity of "hepatic" transaminases in blood serum.

In rare instances in 3 months of treatment there is a cholestasia and hepatitis. At emergence of signs of an abnormal liver function (weakness, persistent nausea, a loss of appetite, an excessive abdominal pain, jaundice, darkening of urine or the decoloured chair) drug should be cancelled.

Purpose of a terbinafin sick psoriasis demands care since it seldom or never тербинафин can provoke an exacerbation of psoriasis.

At treatment terbinafiny it is necessary to follow the general rules of hygiene for prevention of a possibility of repeated infection through linen and footwear. In the course of treatment (in 2 weeks) and at the end of it it is necessary to make antifungal processing of footwear, socks and stockings.

Influence on control of vehicles and mechanisms. There are no data on Terbinafin's influence on ability to control of vehicles and mechanisms.

Use at pregnancy and in the period of a lactation. As researches on safety of use of Terbinafin for pregnant women were not conducted, it is not necessary to appoint drug at pregnancy. Terbinafin is allocated with breast milk therefore its appointment is contraindicated during breastfeeding.

Side effects:

Frequency: very often — more than 1/10, it is frequent — more than 1/100 and less than 1/10, infrequently — more than 1/1000 and less than 1/100, is rare — more than 1/10000 and less than 1/1000, is very rare — less than 1/10000, including separate cases.

From the alimentary system: very often — feeling of overflow of a stomach, a loss of appetite, dyspepsia, nausea, abdominal pain, diarrhea; seldom — disturbance of function of a liver; very seldom — a liver failure, up to a lethal outcome.

From bodies of a hemopoiesis: very seldom — a neutropenia, an agranulocytosis, thrombocytopenia, a pancytopenia.

Allergic reactions: very seldom — anaphylactoid reactions (including a Quincke's disease).

From a nervous system: often — a headache; infrequently — taste disturbance, including an ageusia.
From integuments: very often — skin reactions (including rash, urticaria); very seldom — Stephens-Johnson's syndrome, a toxic epidermal necrolysis, pso-riazopodobny rash, an exacerbation of the available psoriasis, an alopecia.

From a musculoskeletal system: very often — an arthralgia, a mialgiya.

Others: very seldom — fatigue; skin lupus erythematosus, hard currency or their aggravation.

Interaction with other medicines:

Inhibits an isoenzyme of CYP2D6 and breaks metabolism of such drugs as tricyclic antidepressants and selective serotonin reuptake inhibitors (for example, desipramine, флувоксамин), beta adrenoblockers (метопролол, propranolol), antiarrhythmic means (флекаинид, пропафенон), monoamine oxidase inhibitors B (for example, селегилин) and antipsychotic (for example, Chlorpromazinum, a haloperidol) means.

Medicinal drugs inductors of isoenzymes of P450 cytochrome (for example, rifampicin) can accelerate metabolism and removal of a terbinafin from an organism. Medicinal drugs-inhibitors of isoenzymes of P450 cytochrome (for example, Cimetidinum) can slow down metabolism and removal of a terbinafin from an organism. At simultaneous use of these prepart dose adjustment of a terbinafin can be required.

Disturbance of a menstrual cycle at a concomitant use of a terbinafin and oral contraceptives is possible.

Terbinafin reduces clearance of caffeine by 21% and prolongs time of its semi-removal for 31%. Does not influence clearance of phenazone, digoxin, warfarin.

At combined use with the ethanol or drugs possessing a hepatotoxic action there is a risk of development of medicinal damage of a liver.

Contraindications:

- hypersensitivity to a terbinafin or other components of drug;
- chronic or active diseases of a liver;
- chronic renal failure (clearance of creatinine less than 50 ml/min.);
- children's age (up to 3 years) and with body weight to 20 kg (for this dosage form);
- lactation period;
- deficit of lactase, lactose intolerance, glyukozogalaktozny malabsorption.

It is necessary to be careful at:
- a renal failure (with clearance of creatinine more than 50 ml/min.);
- alcoholism;
- oppression of a marrowy hemopoiesis;
- tumors;
- metabolism diseases;
- occlusal diseases of vessels of extremities;
- skin lupus erythematosus or system lupus erythematosus.

Overdose:

Symptoms: a headache, dizziness, nausea, vomiting, pain in epigastric area, the speeded-up urination, rash.

Treatment: actions for drug removal (gastric lavage, reception of absorbent carbon); if necessary — a symptomatic maintenance therapy.

Storage conditions:

In the dry, protected from light place at a temperature not over 25 ºС. To store in the place, unavailable to children. Period of validity: 3 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets on 250 mg. On 7 or 10 tablets in a blister strip packaging from a film of polyvinyl chloride and aluminum foil. 1, 2 or 4 blister strip packagings on 7 tablets or 1, 2 or 3 blister strip packagings on 10 tablets together with the application instruction in a pack from a cardboard.