Terbinafine - instructions for use, doses, side effects, contraindications

Excipients: lactose monohydrate (sugar milk) 43 mg or 86 mg; hydroxypropylcellulose 1.8 mg or 3.6 mg; potato starch 14.2 mg or 28.4 mg; croscarmellose sodium 4.2 mg or 8.4 mg; talc 4.2 mg or 8.4 mg; magnesium stearate 2.1 mg or 4.2 mg.

Description:Tablets white or white with a yellowish hue of color, flat-cylindrical shape with a facet and a risk.

Pharmacotherapeutic group:antifungal agent

ATX: & nbsp

D.01.A.E.15 Terbinafine

Pharmacodynamics:

Terbipaffin is an allylamine that has a broad spectrum of action against fungi that cause skin, hair and nail diseases, including dermatophytes (Trychophyton rubrum, Trychophyton mentagrophytes, Trychophyton vcrrucosum, Trychophyton violaceum, Trychophyton tonsurans, Microsporum canis, Epidermophyton floccosum), as well as yeast fungi of the genus Candida (e.g., C. albicans) and Pityrosporum. In low concentrations terbipafin has a fungicidal effect against dermatophytes, molds and some dimorphic fungi. Activity with respect to yeast fungi, depending on their type, may be fungicidal or fungistatic.

Terbipafin, inhibiting squalepepoxidase in the cell membrane of the fungus (ns related to the cytochrome P450 system), specifically inhibits the early stage of the synthesis of sterols in the fungal cell, which leads to ergosterol deficiency, intracellular squalene accumulation and fungal cell death.

When terbinafine is applied inside the skin, hair and nails, the concentrations of the drug are created to ensure fungicidal action.

Pharmacokinetics:

After oral administration terbinafine well absorbed (more than 70%); The absolute bioavailability of terbinafine due to the "first pass" effect is approximately 50%. After a single administration of terbinafine inwards at a dose of 250 mg, its maximum plasma concentration (Stach) is reached after 1.5 hours and is 1.3 μg / ml. With a constant intake of terbinafine, his Stach increased by an average of 25% more than in a single dose; the iodine area of the concentration-time curve (AUC) has increased by 2.3 times. Based on the increase AUC, you can calculate the effective half-life (30 hours).

Food intake moderately affects the bioavailability of the drug (AUC increases by less than 20%), so there is no need to adjust the dose of terbinafine with simultaneous intake with food.

Terbinafine is largely associated with blood plasma proteins (99%). It quickly penetrates the dermal layer of the skin and is concentrated in the lipophilic stratum corneum. Terbinafine also penetrates into the secretion of the sebaceous glands, which leads to the creation of high concentrations in the hair follicles, hair and in the skin, rich in sebaceous glands. It is also shown that terbinafine penetrates the nail plate in the first few weeks after the initiation of therapy.

Terbinafine is metabolized rapidly and to a significant extent with the participation of at least seven isoenzymes of cytochrome P450, with the main role being played by isozymes CYP2C9, CYP1A2, CYP3A4, CYP2C8 and CYP2C19. As a result of the biotransformation of terbinafine, metabolites are formed that do not possess antifungal activity and are excreted mainly by the kidneys.

Multiple application of terbinafine, leading to an increase in its serum concentration, is accompanied by a three-phase excretion with a finite half-life of about 16.5 days.

There were no changes in the equilibrium concentration of terbinafine in plasma, depending on age.

In pharmacokinetic studies of a single dose of terbinafine in patients with concomitant impairment of renal function (creatinine clearance <50 mL / min) and with liver diseases, the possibility of reducing the clearance of the drug by 50% was demonstrated.

Indications:

Mycosis caused by microorganisms sensitive to terbinafine:

- onychomycosis caused by dermatophytes;

- mycoses of the scalp;

- fungal infections of the skin - treatment of dermatomycosis of the trunk, shins, feet, as well as yeast infections of the skin caused by fungi of the genus Candida (eg, Candida albicans) - In those cases where the localization, severity or prevalence of infection determines the advisability of oral therapy.

Contraindications:

- hypersensitivity to catabinabin or to any other component of the drug;

- children under 3 years old, with a body weight of less than 20 kg (no data on the application);

- severe, chronic or active liver disease;

- renal dysfunction (creatinine clearance less than 50 ml / min or creatinine concentration in the blood serum of more than 300 μmol / l), t. the use of the drug in this category of patients has not been sufficiently studied;

- lactose intolerance, lactase deficiency and glucose-galactose malabsorption.

Carefully:

If you have one of these diseases, always consult a doctor before using the drug.

When using the drug, care must be taken for patients with impaired liver function.

Care must be taken when using the drug in patients with oppression of bone marrow hematopoiesis, cutaneous lupus erythematosus or systemic lupus erythematosus.

The drug should be used with caution in patients with such concomitant diseasesas psoriasis or lupus erythematosus due to possible exacerbation of these diseases.

Pregnancy and lactation:

Clinical experience with the use of terbinafine in pregnant women is limited, so do not use the drug during pregnancy, except when the expected benefit to the mother from the therapy exceeds the potential risk to the fetus.

Terbinaphy is excreted in breast milk, so the drug is contraindicated in the period of breastfeeding.

Dosing and Administration:

The drug is taken orally, regardless of food intake, with a small amount of water. It is advisable to take the drug at the same time. The duration of treatment depends on the indication and severity of the course of the disease.

Adults

250 mg once a day.

Infections of the skin

Recommended duration of treatment: dermatomycosis of the feet (interdigital, plantar or but type of socks) - 2-6 weeks; dermatomycosis of the trunk, shins - 2-4 weeks; Candidiasis of the skin - 2-4 weeks. Complete disappearance of manifestations of infection and complaints associated with it can occur no earlier than a few weeks after mycological cure.

Hair and scalp infections

Recommended duration of treatment: mycosis of the scalp - 4 weeks. Mycoses of the scalp are mainly seen in children.

Onychomycosis

Duration of treatment is in most patients from 6 to 12 weeks. When oiichomycosis of brushes in most cases, 6 weeks of treatment is sufficient. When onychomycosis of the feet in most cases, 12 weeks of treatment are sufficient. Some patients who have a reduced rate of nail growth may need longer treatment. The optimal clinical effect is observed several months after mycological cure and discontinuation of therapy. This is determined by the heme period of time, which is necessary for the growth of a healthy nail.

Use in children

Data on the use of the drug in children under 3 years of age (whose body weight is usually less than 12 kg) is not available. The use of the drug for treatment in children weighing less than 20 kg is not recommended in view of the inability to adequately select a dose. The use in children from 3 to 12 lay with a body weight of more than 20 kg is advisable only if the positive expected effect of therapy exceeds the potential risk of side effects. Duration of treatment and dose depend on the weight of the child.In children older than 3 years, the drug is prescribed 1 time per day. Single dose is: for children with a body weight of 20 to 40 kg - 125 mg (1/2 tablet 250 mg); more than 40 kg - 250 mg.

Use in elderly patients

There is no reason to assume that for patients of advanced age it is required to change the dosage regimen of the drug or that they have side effects,from those in patients of younger age. In case of use in this age group of the drug in tablets, the possibility of concomitant impairment of liver or kidney function should be considered.

Side effects:

Terbinafine as a whole is well tolerated. Side effects are usually mild or moderate and are transient. The frequency of side effects was estimated as follows: very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); Very rarely (<1/10000), the frequency is unknown (the incidence of side effects can not be estimated based on available data). Violations from the blood and lymphatic system: infrequently, anemia; very rarely - neutropsy, agranulocytosis, pancytopenia, thrombocytopenia.

Immune system disorders: very rarely - anaphylactoid reactions (including angioedema), cutaneous and systemic lupus erythematosus (or their exacerbation), frequency is unknown - anaphylactic reactions, a syndrome similar to serum sickness. Disorders of the psyche: often - depression; infrequent anxiety.

Impaired nervous system: very often - headache; often - dizziness, taste disorders, up to their loss (usually the recovery occurs within a few weeks after cessation of treatment), infrequently - paresthesia, hyiesthesia; frequency is unknown - loss of smell, including for a long period of time, a decrease in smell.

Disorders from the side of the organ of vision: infrequently - impaired vision; frequency unknown - blurred vision, decreased visual acuity.

Hearing disorders and labyrinthine disturbances: infrequently, noise in the ears; frequency unknown - hearing loss, hearing loss.

Vascular disorders: frequency is unknown - vasculitis.

Disorders from the gastrointestinal tract: very often - bloating, decreased appetite, dyspepsia, nausea, mild abdominal pain, diarrhea, frequency unknown - pancreatitis.

Disorders from the liver and bile ducts: rarely hepatobiliary dysfunction (mainly of a cholestatic nature), including hepatic insufficiency, including rare cases of severe hepatic insufficiency (some with fatal outcome or requiring liver transplantation); hepatitis, jaundice, holsstasis, increased activity of "liver" transaminases. In most cases, when hepatic insufficiency developed, patients had serious comorbid conditionsdark diseases and the causal relationship of hepatic insufficiency with terbinafine was questionable;

Disturbances from the skin and subcutaneous tissues: very often - a rash, urticaria, infrequently - photosensitivity reactions; very rarely - Stevens-Johnson syndrome, toxic epidermal pecrolisis; acute generalized exanthematous pustulosis, erythema multiforme, toxic skin rash, exfoliative dermatitis, bullous dermatitis, psoriasis-like rashes or exacerbation of psoriasis, alopecia; frequency unknown - drug rash with eosinophilia and systemic symptoms (rash, swelling, fever, and enlarged lymph nodes).

Disturbances from the musculoskeletal and connective tissue: very often - arthralgia, myalgia, the frequency is unknown - rhabdomyolysis.

General disorders: often - a feeling of fatigue, infrequently - fever, frequency is unknown - flu-like syndrome.

Laboratory and instrumental data: infrequently - weight loss (secondary to the violation of taste sensations), the frequency is unknown - increased activity of krsatinphosphokinase.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:Symptoms: headache, nausea, epigastric pain and dizziness. Recommended in case of an overdose treatment includes measures to remove the drug, primarily by prescribing activated charcoal and washing the stomach; if necessary, conduct symptomatic and supportive therapy.

Interaction:

The effect of other drugs on terbinafine

The plasma clearance of terbinafine can be accelerated under the influence of drugs - inducers of metabolism, and suppressed under the influence of inhibitors of cytochrome P450.If it is necessary to simultaneously apply the above drugs and terbinafine, a corresponding correction of the dosage regimen of the latter may be required. Cimetidine can enhance the action of terbinafine or increase its concentration in the plasma. Cimetidine reduces terbinafine clearance by 33%.

Fluconazole increases C max and AUC terbinafine by 52% and 69%, respectively, due to oppression of the isoenzyme CYP2C9 and CYP3A4. Such an increase in terbinafine exposure may occur with the use of other isozyme inhibitory drugs CYP2C9 and CYP3A4, for example ketoconazole and amiodarone.

Rifampicin can relax the action of terbinafine or reduce its concentration in the plasma. Rifampicin increases the terbinafine clearance by 100%.

The effect of terbinafine on other drugs

Terbinafine inhibits metabolism mediated by isoenzyme 2D6 (CYP2D6). These data may be clinically relevant for those drugs that are metabolized predominantly by this enzyme: tricyclic antidepressants, run-adrenoblockers, selective serotonin reuptake inhibitors, antiarrhythmics (1A, 1B and 1C class) and monoamine oxidase B type inhibitors, if the concomitant drug has a small range of therapeutic concentration.

Terbinafine reduces the clearance of desipramip by 82%.

In studies on healthy volunteers with active metabolism of dextrofetorphan (an antitussive agent and a substrate CYP2D6) terbinafine increased the metabolic coefficient of dextromethorphan / dextrorphan in urine 16-97 times. In this way, terbinafine in persons with high isofermptic activity CYP2D6 can reduce the activity of the latter.

Terbinafine reduces caffeine clearance by intravenous administration at 19%.

Drug Interactions, not rendering or having an insignificant influence

Terbinafine has little potential for suppressing or enhancing the clearance of most drugs that are metabolized by the cytochrome P450 system (eg, terfenadine, triazolam, tolbutamide or oral contraceptives), except for those that are metabolized with CYP2D6. Terbinafine does not affect the clearance of phenazone or digoxin.

Terbinafine has no significant effect on the pharmacokinetics of fluconazole.There were no clinically significant interactions between terbinafine and cotrimoxazole components (trimethoprim and sulfamethoxazole), zidovudine, or theophylline.

With the simultaneous administration of terbinafine with oral contraceptives, a menstrual cycle disorder is possible.

Terbinafine may reduce serum concentrations or the severity of the clinical effects of the following drugs Terbinafine increases the clearance of cyclosporine by 15%.

Interaction with food and beverages

Food has a slight effect on the bioavailability of terbinafine (an increase AUC<20%), that does not require a change in the dose of the drug.

Special instructions:

Irregular application or early termination of treatment will attempt to develop a recurrence of the disease.

Before the application of terbinafine in tablets, it is necessary to perform an analysis of liver function. Hepatotoxicity can occur both in patients with previous liver diseases, and without them. During therapy, a periodic study of liver function is recommended (4-6 weeks after the start of treatment). Treatment should immediately be discontinued in case of increased activity of "liver" samples.Patients prescribing the drug should be warned that it is necessary to immediately inform the attending physician of the appearance of such symptoms as persistent nausea, loss of appetite, a feeling of fatigue, vomiting, pain in the right hypochondrium, jaundice, dark urine or light feces . In case of appearance of such symptoms, it is necessary to immediately stop taking the drug and conduct a study of liver function.

Serious skin reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms) were extremely rare when terbinafine was used.

When using the drug in tablets, extremely rare changes in the cellular composition of the crope (neutropenia, agranulocytosis, thrombocytopenia, pancytopenia) were noted. In the case of qualitative or quantitative changes in the blood constituents, the cause of the impairment should be established and the issue of reducing the dose of the drug or, if necessary, discontinuing the therapy with the drug should be considered.

'Herbathin suppresses metabolism mediated by enzyme 2D6 (CYP2D6), therefore, continuous monitoring of patients receiving concurrently with terbinafine treatment with drugs predominantly metabolized with the participation of this enzyme (such as tricyclic antidepressants, бста-адреноблокаторы, selective serotonin reuptake inhibitors, antiarrhythmic drugs of the class 1C and type B monoamine oxidase inhibitors) in the case where the concomitant drug has a small range of therapeutic concentration.

Effect on the ability to drive transp. cf. and fur:The effect of the drug on the ability to drive vehicles and work with mechanisms has not been studied. When dizziness develops against the background of drug therapy, patients should not drive vehicles and / or work with mechanisms.

Form release / dosage:

Tablets 125 mg and 250 mg

For 7 or 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 14, 28, 50 or 100 tablets in cans of polymeric.

Each bank or 2, 4 contour cell packs of 7 tablets or 2, 3, 5, 10 contour cell packs of 10 tablets together with instruction but use are swept into a pack of cardboard box.

Packaging:(10) - packings cellular planimetric (10) - packs cardboard
(10) - packings, cellular, outline (2) - packs, cardboard
(10) - packings, cellular, outline (3) - packs, cardboard
(10) - packings, cellular planimetric (5) - packs cardboard
(100) - polymer cans (1) - packs of cardboard
(14) - polymer cans (1) - packs cardboard
(28) - polymer cans (1) - cardboard packs
(50) - polymer cans (1) - cardboard packs
(7) - packings, cellular, outline (2) - packs, cardboard
(7) - packings, cellular, outline (4) - packs, cardboard

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children

Shelf life:

3 thYes.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002844

Date of registration:27.01.2015

The owner of the registration certificate:MEDISORB, CJSC MEDISORB, CJSC Russia

Manufacturer: & nbsp

MEDISORB, CJSC Russia

Information update date: & nbsp18.09.2015

Illustrated instructions

Instructions

Terbinafine (Terbinafine)