Lamisil, tablets 250 mg 14 pcs

LAMISIL is a broad spectrum antifungal, fungistatic, fungicidal.

Pharmacodynamics

Terbinafine is an allylamine, which has a broad spectrum of action against fungi that cause skin, hair and nail diseases, including dermatophytes.Dermatophytes, such as T. rubrum, T. mentagrophytes, T. verrucosum, T. tonsurans, T. violaceum, Microsporum (such as M. canis), Epidermophyton floccosum, as well as yeasts of the Candida (such as C. albicans) and Pityrosporum. In low concentrations, terbinafine has fungicidal effect against dermatophytes, molds and some dimorphic fungi. Activity against yeast fungi, depending on their species, may be fungicidal or fungistatic.

Terbinafine specifically inhibits the early stage of sterol biosynthesis in the fungus cell. This leads to a deficit of ergosterol and to intracellular accumulation of squalene, which causes cell death of the fungus. The action of terbinafine is performed by inhibiting the squaleneepoxidase enzyme in the cell membrane of the fungus. This enzyme does not belong to the cytochrome P450 system.

When Lamisil® is administered orally, concentrations of the drug are created in the skin, hair and nails to provide fungicidal action.

Pharmacokinetics

After oral administration, terbinafine is well absorbed (>70%); the absolute bioavailability of terbinafine due to the first-pass effect is approximately 50%. After a single oral dose of 250 mg terbinafine, its Cmax in plasma is reached after 1.5 hours and is 1.3 µg/ml. When terbinafine was taken continuously, its Cmax increased by an average of 25% compared to a single dose; the AUC increased 2.3-fold. Based on the increase in AUC, an effective T1/2 can be calculated – 30 h. Food intake has little effect on bioavailability of the drug (AUC increased by less than 20%), therefore no correction of the dose of Lamisil® preparation is required in case of concomitant use with food.

Terbinafine is largely bound to blood plasma proteins (99%). It quickly penetrates through the dermal layer of the skin and concentrates in the lipophilic stratum corneum. Terbinafine also penetrates into the sebaceous gland secretion, resulting in high concentrations in hair follicles, hair and sebaceous gland-rich skin. Terbinafine has also been shown to penetrate the nail plates in the first few weeks of therapy.

Terbinafine is metabolized rapidly and to a significant extent with the participation of at least 7 cytochrome P450 isoenzymes, with CYP2C9, CYP1A2,CYP3A4, CYP2C8 and CYP2C19 playing a major role. As a result of biotransformation of terbinafine metabolites are formed that have no antifungal activity and are excreted mainly with the urine.

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

In pharmacokinetic studies of a single dose of Lamisil® in patients with concomitant renal dysfunction (creatinine Cl

Indications

Active ingredient

Composition

1 tablet contains:

Active substance:

Terbinafine (in the form of hydrochloride)250 mg;

Associates:

magnesium stearate;

colloidal anhydrous silicon dioxide;

methylhydroxypropylcellulose;

sodium glycolate starch;

MCC.

How to take, the dosage

Ingestion.

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

In children

There are no data on the use of the drug in children under 2 years of age (body weight usually less than 12 kg).

The drug is prescribed once a day. The single dose depends on body weight and is as follows: for children with body weight less than 20 kg – 62.5 mg; from 20 to 40 kg – 125 mg; over 40 kg – 250 mg. In children over 2 years old the tolerability of oral Lamisil® is good.

Adults

The recommended dose is 250 mg once daily.

Infections of the skin

Recommended duration of treatment: dermatomycosis of the feet (interfinger, plantar or sock type) – 2-6 weeks; dermatomycosis of the trunk, shins – 2-4 weeks; skin candidiasis – 2-4 weeks.

The complete disappearance of manifestations of infection and complaints associated with it may occur not earlier than a few weeks after mycological cure.

Hair and scalp infections

The recommended duration of treatment: scalp mycosis – 4 weeks. Mycoses of the scalp are observed mainly in children.

Onychomycosis

The duration of treatment in most patients is 6 to 12 weeks. With onychomycosis of the hands, 6 weeks of treatment is sufficient in most cases. For onychomycosis of the feet, 12 weeks of treatment is sufficient in most cases. Some patients with reduced nail growth rate may require longer treatment. The optimal clinical effect is seen several months after mycological cure and discontinuation of therapy. This is determined by the period of time needed for the healthy nail to grow back.

Application in the elderly. There is no reason to believe that the dosing regimen should be changed in elderly patients or that they have different side effects than younger patients. The possibility of concomitant hepatic or renal dysfunction should be considered when using the drug in this age group in tablets.

Interaction

The effect of other drugs on terbinafine. Plasma Cl of terbinafine may be accelerated under the influence of drugs – metabolism inducers, and suppressed under the influence of cytochrome P450 inhibitors. If it is necessary to use the above mentioned drugs and Lamisil® simultaneously it may be necessary to adjust the dosage regimen of the latter accordingly.

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

Rifampicin may decrease the effect of terbinafine or decrease its plasma concentration. Rifampicin increases Cl terbinafine by 100%.

The effect of terbinafine on other drugs. The results of studies conducted in vitro and in healthy volunteers show that terbinafine has little potential to inhibit or increase Cl of most drugs that are metabolized with participation of cytochrome P450 system (such as terfenadine, triazolam, tolbutamide or oral contraceptives), except for those that are metabolized with CYP2D6.

Terbinafine has no effect on Cl antipyrine or digoxin.

There have been reports of several cases of menstrual irregularities in patients taking Lamisil® together with oral contraceptives, although the incidence of these irregularities is not higher than the average incidence in patients taking oral contraceptives alone.

Terbinafine may increase the effect of caffeine or increase its plasma concentrations. Terbinafine reduces the Cl of caffeine by 19% when administered by IV.

It has been shown in in vivo and in vitro studies that terbinafine inhibits the metabolism mediated by the enzyme 2D6 (CYP2D6). These data may be clinically relevant for those drugs which are metabolized predominantly by this enzyme: tricyclic antidepressants, beta-adreno-blockers, selective serotonin reuptake inhibitors, antiarrhythmic class (1A, 1B and 1C) drugs and MAO type B inhibitors – if the drug used simultaneously has a low therapeutic concentration range.

Terbinafine reduces Cl desipramine by 82%.

Terbinafine may weaken the effect of cyclosporine and decrease its plasma concentration. Terbinafine increases the Cl of cyclosporine by 15%.

Contraindications

Hypersensitivity to terbinafine or any other ingredient of the drug.

Side effects

Hematopoietic system: very rarely – neutropenia, agranulocytosis, pancytopenia. In very rare cases during drug administration qualitative or quantitative changes in blood cells (neutropenia, agranulocytosis, thrombocytopenia, pancytopenia) have been observed. In case of qualitative or quantitative changes of blood cells the cause of disorders should be determined and the decision to reduce the drug dose or, if necessary, to discontinue therapy with Lamisil® should be considered.

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

Nervous system disorders: often – headache; sometimes – disorders of the sense of taste, including their loss (usually recovering within a few weeks after discontinuation of treatment); very rarely – dizziness, paresthesia, hypoesthesia. There are individual reports of cases of prolonged disorders of the sense of taste. In some cases during the treatment of the drug a decrease in food intake was noted, which led to a significant weight loss.

Hepatobiliary system disorders: rare – hepatobiliary dysfunction (mainly of cholestatic nature), including very rare cases of severe liver failure (some with fatal outcome or requiring liver transplantation). In most cases where liver failure developed, patients had severe underlying systemic diseases and the causal relationship of liver failure to Lamisil® administration was questionable.

Digestive system disorders: very common – feeling of stomach fullness, loss of appetite, dyspepsia, nausea, mild abdominal pain, diarrhea.

Skin and subcutaneous tissue: very common – mild skin reactions (rash, urticaria); very rare – serious skin reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis); psoriasis-like skin rashes or exacerbation of psoriasis. Very rare cases of hair loss have been reported, although a causal relationship of this phenomenon with taking the drug has not been established. If a progressive skin rash develops, treatment should be discontinued.

Skeletal-muscular system disorders: very often – arthralgia, myalgia.

Others: very rare – feeling of fatigue.

Overdose

Symptoms: there have been reports of several cases of overdose (the taken dose of the drug was up to 5 g) in which headache, nausea, epigastric pain and dizziness were noted.

Treatment: symptomatic and supportive therapy, measures for elimination of the drug, primarily by prescription of activated charcoal and gastric lavage.

Similarities