Allylamine which has a broad spectrum of activity against fungi which cause diseases of the skin, hair and nails, including dermatophytes such as primobolan depot 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,primobolan depot 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 primobolan depot system.When assigning primobolan depot inside the skin, hair and nails are drug concentration providing fungicidal activity.
After oral administration, terbinafine is well absorbed (> 70%); the absolute bioavailability of terbinafine due to the effect of “first pass” is about 50%. After receiving a single oral dose of terbinafine 250 mg its maximum concentration is reached after 1.5 hours in plasma (Cmax) and is 1.3 ug / ml. When it postoyannno receiving terbinafine Cmax increased on average by 25%, compared to a single dose; AUC increased 2.3-fold. Based on the increased AUC, we can calculate the effective half-life (30 hours). Ingestion marginally affects drug bioavailability (AUC is increased by at least 20%), and therefore requires no dose adjustment Lamizila® while taking 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 primobolan depot 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 primobolan depot and substantially, with the participation of at least seven isoenzymes of cytochrome P450, 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, single dose Lamizila® in patients with underlying renal impairment (creatinine clearance <50 mL / min) and liver disease have shown the possibility of reducing the clearance of the drug by 50%.
- Onychomycosis caused by dermatophytes fungi.
- Fungal infections of the scalp.
- Fungal skin infections – treatment of primobolan depot tinea of the body, legs, feet, and yeast infections of the skin caused by fungi of the genus of Candida (eg, of Candida albicans) – in cases where localization, severity or prevalence of infection determine the feasibility of oral therapy.Note: unlike Lamizila® topical terbinafine oral not effective in pityriasis versicolor.CONTRAINDICATIONS
Increased sensitivity to terbinafine or to any ingredient of the drug.
Terbinafine is not recommended for patients with chronic or active liver disease. Prior to his appointment Lamizila® tablets need 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 terbinafine should be warned that you should immediately inform your doctor of the occurrence primobolan depot in patients receiving the drug symptoms such as persistent nausea, anorexia, fatigue, vomiting, right upper quadrant pain, 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.
Pregnancy and lactation
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 Lamizila® 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 terbinafine into, should not breastfeed.
DOSAGE AND ADMINISTRATION
The duration of treatment depends on the indication and the severity of the disease.
Data on the use of the drug in children primobolan depot 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; from 20 to 40 kg – 125 mg; 40 kg – 250 mg. In children older than 2 years Lamizila® tolerability of oral good.
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.
Tinea torso, legs: 2-4 weeks.
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:
Mycosis of the scalp:. 4 weeks
Fungal infections of the scalp mostly seen in children.
The duration of treatment in most patients is 6 to 12 weeks. When onychomycosis brushes in most cases enough to 6 weeks of treatment. When onihomi goat-stop in most cases quite 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.
Use in patients with impaired renal function
Patients with renal impairment (creatinine clearance less than 50 mL / min and concentration of serum creatinine 300 umol / L), the dose should be reduced by 2 times.
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.
Terbinafine 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 often” (> 1/10), “often” (from> / 100 <1/10), “sometimes” (> 1/1000 <1/100), ” rarely “(> 1/10000 <1/1000),” very rarely “(<1/10000), including isolated posts.
From hemopoiesis system: very rarely – neutropenia, agranulocytosis, thrombocytopenia.
Immune system: very rare – anaphylactoid reactions (including angioedema), cutaneous and systemic lupus erythematosus
From the nervous system: often – headache; sometimes primobolan depot – a violation of taste sensations, including their loss (typically recovery occurs within a few weeks after cessation of treatment). 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.
Liver: rare – 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 reception Lamizila® was questionable.
On the part of the gastrointestinal tract (GIT): 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) very seldom – 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 Lamizilom®.
From the musculoskeletal system: very often – arthralgia, myalgia.
Other: very rarely – fatigue.
There are reports of a few cases of overdose (accepted dose was 5 g), in which the observed headache, nausea, epigastric pain and dizziness.
Recommended in case of overdose, treatment includes measures to eliminate the drug, primarily by the appointment of activated charcoal and gastric lavage; if necessary, symptomatic and supportive therapy.
interaction with other medicinal products and other forms of
Effect of other medicinal products on terbinafine
The plasma clearance of 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 Lamizila® 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 clearance of terbinafine by 33%.
Rifampicin may impair the action of terbinafine or reduce its concentration in plasma. Rifampicin increased the clearance of terbinafine by 100%.
Effect of terbinafine on other drugs
Studies conducted in vitro and in healthy primobolan depot volunteers show that terbinafine has little capacity to inhibit or enhance the clearance of most drugs that are metabolized by the participation of cytochrome P450 (eg, terfenadine, triazolam, tolbutamide or oral contraceptives), except for those which are metabolized by the CYP2D6.
Terbinafine does not influence the clearance of antipyrine or digoxin.
There are reports of several cases of violation of the menstrual cycle in patients taking terbinafine, 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 decreases the clearance of caffeine administered intravenously by 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 drugs of class 1C and inhibitors mono-oxidase type B – in case applied simultaneously preparation It has a small range of therapeutic concentrations.