Expiration date: 12/2025

Structure and Composition:

Tablets. 1 tablet contain terbinafine (in hydrochloride salt form) 250 mg

Excipients: magnesium stearate, silica colloidal anhydrous sodium starch glycolate methylhydroxypropylcellulose MCC

in blister 7 or 14 pieces. 1 a cardboard pack (7 and 14 pcs.) or 2 (14 pcs.) blisters.

Description pharmaceutical form:

Round biconvex tablets from white to white with a yellowish shade, bevelled on one side there is the risk and the inscription «Lamisil 250" (in a circle). The surface is smooth or slightly rough.

Pharmacokinetics:

After oral administration, terbinafine is well absorbed (> 70%) the absolute bioavailability of terbinafine as a result of first-pass effect of about 50%. After receiving a single oral dose of terbinafine 250 mg its Cmax achieved in 1.5 hours, and the plasma is 1.3 g / ml. In its continuous admission terbinafine Cmax increased on average by 25%, compared to the single dose AUC increased by 2.3 times. Based on the increased AUC, we can calculate the effective T1 / 2 -. 30 hours Ingestion marginally affects the bioavailability (AUC is increased by at least 20%), and therefore does not require dosage adjustment Lamisil drug when taken with food.

Terbinafine largely bound to plasma proteins (99%). It quickly penetrates the dermal layer of the skin, and concentrates in the lipophilic stratum corneum. Terbinafine is also penetrates the sebum, which results in a high concentration in the hair follicles, the hair and the skin rich in sebaceous glands. We also show that terbinafine penetrates the nail plate in the first few weeks after beginning therapy.

Terbinafine is metabolised rapidly and substantially, with the participation of at least 7 of cytochrome P450 isoenzymes, with the main role is played isoenzymes CYP2C9, CYP1A2, CYP3A4, CYP2C8 and CYP2C19. The resulting biotransformation terbinafine metabolites formed without having antifungal activity and can be output primarily with urine.

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

In pharmacokinetic studies, a single dose of the drug Lamisil in patients with underlying renal impairment (Cl creatinine <50 ml / min) and liver diseases was shown to reduce the possibility of Cl product by 50%.

Description of the pharmacological actions:

Terbinafine is an allylamine which has a broad spectrum of activity against fungi which cause diseases of the skin, hair and nails, including dermatophytes, such as by Trichophyton (eg T. rubrum, T. mentagrophytes, T. verrucosum, T. tonsurans, T. violaceum), Microsporum (eg M. canis), Epidermophyton floccosum, and yeasts of the genus Candida (eg C. albicans ) and Pityrosporum. At low concentrations of terbinafine has fungicidal activity against dermatophytes, molds and certain dimorphic fungi. Activity against yeast fungi, depending on their type, may be a fungicidal or fungistatic.

Terbinafine specifically inhibits the early stage of the biosynthesis of sterols in fungal cells. This leads to a deficiency of ergosterol and to an intracellular accumulation of squalene, which causes death of fungal cells. Terbinafine action effected by inhibition of the enzyme squalene epoxidase in the cell membrane of the fungus. This enzyme does not belong to the cytochrome P450 system.

When assigning Lamisil drug into the skin, hair and nails are drug concentration providing fungicidal activity.

Indications:

• onychomycosis caused by dermatophytes fungi
  
• fungal infections of the scalp
  
• fungal skin infections - treatment of tinea of ??the body, legs, feet, and yeast infections of the skin caused by fungi of the genus Candida (eg Candida albicans) - in cases where localization, severity or prevalence of infection determine the feasibility of oral therapy.
  

Note: Unlike the drug Lamisil topical Lamisil drug for oral administration is not effective in pityriasis versicolor.

Contraindications:

Increased sensitivity to terbinafine or to any ingredient of the drug.

Carefully:

renal impairment (Cl creatinine less than 50 mL / min or serum creatinine concentration in the serum of more than 300 umol / L) - for use of the drug are poorly understood, it is not recommended in these patients

chronic or active liver disease - before prescribing the drug Lamisil tablets is necessary to determine whether the patient's previous liver disease. Hepatotoxicity may occur in patients with liver diseases previous or without them. Patients who are prescribed the drug Lamisil should be warned that you should immediately inform your doctor about the origin of the intake of these symptoms the drug as persistent nausea, anorexia, fatigue, vomiting, pain in the right upper quadrant, jaundice, dark urine or light cal. In the event of such symptoms should immediately stop taking the drug and to conduct a study of liver function.

Application of pregnancy and breastfeeding:

These experimental studies do not suggest the presence of adverse events in relation to fertility and of toxic effects on the fetus. Since clinical experience with the drug Lamisil in pregnant women is very limited, you should not use the drug during pregnancy except in cases where the expected benefits of therapy outweighs the potential risk.

Terbinafine is excreted in breast milk, therefore women receiving the drug Lamisil inside, should not breastfeed.

Side effect:

Lamisil drug was generally well tolerated. Side effects are usually mild or moderately expressed and are transient in nature. Below are the adverse events observed in clinical trials or after the drug on the market.

In assessing the incidence of adverse events following grading used: very common (& ge1 / 10), often (& ge1 / 100, <1/10), sometimes (& ge1 / 1000, <1/100), rarely (& ge / 10,000, <1 / 1000), very rare (<1/10000), including isolated reports.

From hemopoiesis system: very rarely - neutropenia, agranulocytosis, pancytopenia. In very rare cases, the use of the drug noted the development of qualitative or quantitative changes of blood cells (neutropenia, agranulocytosis, thrombocytopenia, pancytopenia). In the case of qualitative or quantitative changes in the blood cells must determine the cause of disturbances and consider lowering the dose of the drug or, if necessary, on the termination of therapy with Lamisil.

Immune system: very rare - anaphylactoid reactions (including angioedema), cutaneous and systemic lupus erythematosus.

From the nervous system: often - headache sometimes - taste disturbance, including their loss (typically recovery occurs within a few weeks after cessation of treatment) is very rare - dizziness, paraesthesia, hypoesthesia. There are some reports of cases of prolonged taste disturbance. In some cases in patients receiving the drug showed a decrease in food intake, which resulted in a significant reduction in weight.

On the part of the hepatobiliary system: rarely - hepatobiliary dysfunction (primarily cholestatic nature), including very rare cases of serious liver failure (some with a fatal outcome, or requiring liver transplant). In most cases, when developed liver failure, patients had serious concomitant systemic disease and the causal link of liver failure with taking Lamisil was uncertain drug.

From the digestive system: very often - a sense of fullness, loss of appetite, dyspepsia, nausea, mild abdominal pain, diarrhea.

Skin and subcutaneous tissue: very often - not heavy skin reactions (rash, urticaria) are very rare - serious skin reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis), psoriasiform rash or exacerbation of psoriasis. Very rarely, there have been cases of hair loss, although a causal link with the administration of the drug has not been established. If progressive skin rash develops, treatment should be discontinued.

From the musculoskeletal system: very often - arthralgia, myalgia.

Other: very rarely - fatigue.

Drug Interactions:

Effect of other medicinal products on terbinafine. Plasma Cl terbinafine may be accelerated under the influence of drugs - inducers of metabolism and suppressed under the influence of inhibitors of cytochrome P450. If necessary, the simultaneous application of the above drugs and Lamisil medication and may require appropriate correction dosing regime of the latter.

Cimetidine may increase the effects of terbinafine or increase its concentration in plasma. Cimetidine reduces the Cl of terbinafine by 33%.

Rifampicin may impair the action of terbinafine or reduce its concentration in plasma. Rifampicin increases Cl terbinafine by 100%.

Effect of terbinafine on other drugs. Studies conducted in vitro and in healthy volunteers show that terbinafine has little capacity to inhibit or enhance Cl most drugs that are metabolized by the participation of cytochrome P450 (eg terfenadine, triazolam, tolbutamide or oral contraceptives), except that metabolized by the CYP2D6.

Terbinafine does not affect Cl antipyrine or digoxin.

There are reports of several cases of violation of the menstrual cycle in patients taking the drug Lamisil together with oral contraceptives, although the incidence of these disorders is not higher than the average rate of such disorders in patients taking only oral contraceptives.

Terbinafine may increase the effects of caffeine or increase its concentration in plasma. Terbinafine Cl reduces caffeine with a / in the introduction of 19%.

In studies in vivo and in vitro have shown that terbinafine inhibits metabolism mediated by the enzyme 2D6 (CYP2D6). These data may be clinically important for those drugs that are metabolized primarily by the enzyme: tricyclic antidepressants, beta-blockers, selective serotonin reuptake inhibitor, antiarrhythmic drug classes (1A, 1B and 1C) and MAO inhibitors in type - in the case, if the drug is used at the same time has a small range of therapeutic concentrations.

Terbinafine reduces the Cl desipramine by 82%.

Terbinafine may weaken the effect of cyclosporine, and reduce its concentration in plasma. Terbinafine Cl cyclosporin increases by 15%.

Dosage and administration:

Inside.

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

Children

Data on the use of the drug in children younger than 2 years (body weight which is usually less than 12 kg) are not available.

The drug is administered 1 time per day. Single dose depends on the body weight and is: for children weighing less than 20 kg - 62.5 mg of 20 to 40 kg - 125 mg 40 kg - 250 mg. In children older than 2 years tolerability of the drug Lamisil oral good.

Adults

The recommended dose - 250 mg 1 time per day.

Infections of the skin

The recommended duration of treatment: Tinea pedis (interdigital, plantar or by type of socks) - 2-6 weeks ringworm of the body, legs - 2-4 weeks of skin candidiasis - 2-4 weeks.

Complete disappearance of the manifestations of infection and complaints associated with it, may occur no earlier than a few weeks after mycological cure.

Infections hair and scalp

The recommended duration of treatment: fungal infection of the scalp - 4 weeks. Fungal infections of the scalp mostly seen in children.

Onychomycosis

The duration of treatment in most patients - from 6 to 12 weeks. In onychomycosis brushes in most cases enough to 6 weeks of treatment. In onychomycosis stop in most cases enough to 12 weeks of treatment. Some patients who have a decreased rate of nail growth, may require longer treatment. The optimal clinical effect is seen some months after mycological cure and cessation of therapy. This is determined by the period of time that is required for regrowth of healthy nail.

The use in the elderly. There is no reason to assume that the elderly need to change the drug dosage regimen, or that they have marked side effects that differ from those of younger patients. In the case of use in this age group of the drug in tablets should consider the possibility of concomitant abnormal liver or renal function.

Overdose:

Symptoms: There are reports of a few cases of overdose (accepted dose was 5 g), in which the observed headache, nausea, epigastric pain and dizziness.

Treatment: symptomatic and supportive therapy, for the removal of the drug activities, primarily through the appointment of activated charcoal and gastric lavage.

Special instructions:

It was shown that terbinafine inhibits metabolism mediated by the enzyme 2D6 (CYP2D6). It is therefore necessary to carry out continuous monitoring of patients receiving simultaneously with the drug Lamisil treatment with drugs predominantly metabolized with the participation of the enzyme (such as tricyclic antidepressants, beta-blockers, selective serotonin reuptake inhibitors, antiarrhythmic drugs class 1C and MAO inhibitors type B) in the case of if the drug is used at the same time has a small range of therapeutic concentrations.

Effects on ability to drive vehicles and / or operate machinery. Influence of Lamisil drug on the ability to drive vehicles and operate machinery has not been studied. With the development of dizziness on the background of drug therapy, patients should not drive vehicles and / or operate machinery.