Terbinafin

General characteristics. Structure:

Active agent: a terbinafina of a hydrochloride in terms of тербинафин 125 mg and 250 mg;

excipients: hypro rod (hydroxypropyl cellulose), calcium stearate, silicon dioxide colloid (aerosil), croscarmellose sodium (primelloza), cellulose microcrystallic.

Description: Tablets of color, white or white with a yellowish shade, ploskotsilindrichesky, with a facet and risky.

Pharmacological properties:

Pharmacodynamics. Terbinafin treats group of allylamines, possesses a wide range of antifungal action. In low concentration renders fungicidal action on Trychophyton dermatophytes (T. rubrum,

T. mentagrophytes, T. tonsurans, T.verruсosum, T.violaceum), Microsporum canis, Epidermophyton floccosum, mold mushrooms (e.g. Scopulariopsis brevicaulis), barmy mushrooms, mainly Candida albicans. On Candida spp mushrooms. and renders their mitselialny forms depending on a species of a mushroom fungicidal or a fungistasis.

Terbinafin breaks an early stage of biosynthesis of the main component of a cellular membrane of a mushroom of ergosterol by skvalenepoksidaza enzyme inhibition.

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

Pharmacokinetics. At oral administration it is well absorbed, in 0,8 hours a half of the accepted dose is absorbed; in 4,6 hours a half of the accepted dose is distributed in an organism. In 1–2 hours after intake of a single dose of 250 mg the maximum concentration of drug in a blood plasma reaches 0,97 mkg/ml. Bioavailability makes 80%. Meal does not influence bioavailability of a terbinafin.

Terbinafin intensively contacts proteins of a blood plasma (99%), is quickly distributed in fabrics, gets into a thermal layer of skin and nail plates. Gets into a secret of sebaceous glands and collects in high concentration in hair follicles, in hair, skin and hypodermic cellulose.

The elimination half-life makes 16–18 h, an elimination half-life of a terminal phase — 200–400 h.

It Biotransformirutsya in a liver to inactive metabolites. Kidneys in the form of metabolites remove 80% of the accepted dose, other part (20%) is removed through intestines.

Does not kumulirut in an organism. The age of patients does not influence pharmacokinetics of a terbinafin, however elimination can decrease at damages of kidneys or a liver, resulting in high concentration of a terbinafin in blood.

It is allocated with breast milk.

Indications to use:

- Mycoses of a pilar part of the head (trichophytosis, microsporia).
- The fungus diseases of skin and nails (onychomycoses) caused by Trychophyton (T. rubrum, T. mentagrophytes, T. verrucosum, T. violaccum), Microsporum (M. сanis, M. gypseum) and Epidermophyton floccosum.
- 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:

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.

Adult:

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

Onychomycoses: 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.

To children:

Usually appoint 125 mg. Duration of treatment of mycoses of a pilar part of the head makes about 4 weeks, at Microsporum canis infection — can be longer.

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.

The elderly patient drug is appointed in the same doses, as the adult.

To patients with a liver and renal failure тербинафин appoint in a dose 125 mg once a day.

Features of use:

Irregular use of a terbinafin or the premature termination of treatment can lead to a disease 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 the onychomycosis the clinical answer confirmed laboratory it is usually observed in several months after mycologic treatment and the termination of a course of treatment that it 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, appetite loss, 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.

Side effects:

Dispepsichesky disturbances (loss of appetite, nausea, diarrhea, feeling of overflow of a stomach, abdominal pain); skin allergic reactions (urticaria, rash); musculoskeletal reactions (arthralgia, mialgiya), aggravation of a current of a system lupus erythematosus.

Disturbances of flavoring feelings, including their loss (recovery happens within several weeks after the treatment termination).

Extremely seldom (with a frequency of 0,01-0,1%) the hepatotoxic action (increase in activity of "hepatic" transaminases, a liver failure) is observed.

Malignant exudative erythema (Stephens-Johnson's syndrome), toxic epidermal necrolysis (Lyell's disease), psoriazopodobny enanthesis, exacerbation of psoriasis, anaphylactoid reactions, agranulocytosis or thrombocytopenia, neutropenia, lymphopenia.

Interaction with other medicines:

Inhibits an isoenzyme of CYP2P6 and interferes with metabolism of such drugs as tricyclic antidepressants and selective serotonin reuptake inhibitors (for example, desipramine, флувоксамин), beta adrenoblockers (метопролол, propranolol), antiarrhythmic means (флекаинид, пропафенон), type monoamine oxidase inhibitors B (for example, селегилин) and antipsychotic (for example, Chlorpromazinum, a haloperidol) means.

Medicines — inductors of isoenzymes of P450 cytochrome (for example, rifampicin) can accelerate removal of a terbinafin from an organism.

Medicines — 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 drugs 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 the period of its semi-removal for 31%. Does not influence clearance of phenazone, digoxin, warfarin.

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

Contraindications:

Hypersensitivity to drug components; chronic or active diseases of a liver, a 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), the lactation period, pregnancy.

With care:
Renal failure (with clearance of creatinine less than 50 ml/min.), alcoholism, oppression of a marrowy hemopoiesis, a tumor, metabolism disease, occlusal diseases of vessels of extremities.

Pregnancy and lactation:
Reception of a terbinafin during pregnancy is contraindicated due to the lack of enough data on its safety during pregnancy. Terbinafin is allocated with breast milk therefore its appointment is contraindicated during breastfeeding.

Overdose:

Symptoms: nausea, vomiting, a headache, dizziness, pains in the lower part of a stomach, in epigastric area, the speeded-up urination.

Treatment: a gastric lavage with the subsequent purpose of absorbent carbon and/or symptomatic therapy.

Storage conditions:

List B. 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 4 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets of 125 mg and 250 mg.

On 7 or 10 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.

On 1, 2, 3, 4 blister strip packagings together with the application instruction place in a pack from a cardboard.