Composition, form of production and packaging
Tablets are almost white, round, biconvex, with a smooth surface on both sides.
1 tab.
terbinafine (in the form of hydrochloride) 250 mg
[PRING] microcrystalline cellulose, sodium carboxymethyl starch, povidone K-30, magnesium stearate, silicon dioxide colloid.
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
Terbinafine belongs to the group of allylamines, it has a wide spectrum of action against fungi that cause skin, hair and nail diseases, including dermatophytes such as Trichophyton (eg T. rubrum, T. mentagrophytes, T. verrucosum, T. tonsurans, T. violaceum), Microsporum (eg M. canis), Epidermophyton floccosum, and yeast fungi of the genus Candida (for example, C. Albicans) and Pityrosporum. At low concentrations terbinafine 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.
Terbinafine specifically suppresses the early stage of biosynthesis of sterols in the fungal cell. This leads to a deficiency of ergosterol and to intracellular accumulation of squalene, which causes death of the fungal cell. The action of terbinafine is carried out by inhibiting the enzyme squalene epoxidase in the cell membrane of the fungus. This enzyme does not belong to the cytochrome P450 system.
When the appointment of Terbifin В® inside the skin, hair and nails are created drug concentrations that 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 administration of terbinafine inwards at a dose of 250 mg, its C max is reached after 1.5 hours and is 1.3 Ојg / ml. With a constant intake of terbinafine, its C maxincreased by an average of 25% more than in a single dose; AUC increased by 2.3 times. Based on the increase in AUC, it is possible to calculate the effective T 1/2(30 hours). Food intake has an insignificant effect on the bioavailability of the drug (AUC increases by less than 20%), so there is no need to adjust the dose of Terbifin В® while taking 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 the secretion of 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 plates 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 the 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 in 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 Terbifin В® in patients with concomitant renal impairment (creatinine clearance <50 ml / min) and with liver diseases, the possibility of reducing the clearance of the drug by 50% was demonstrated.
INDICATIONS
- Mycosis of the scalp;
- onychomycosis caused by mushrooms dermatophytes;
- fungal infections of the skin - treatment of dermatomycosis of the trunk, legs, feet, and yeast infections of the skin caused by fungi of the genus Candida (eg Candida albicans) - in cases where the localization, severity or prevalence of infection determine the advisability of oral therapy.
DOSING MODE
The duration of the course of treatment and the dosage regimen is determined individually and depends on the localization of the process and the severity of the disease. Adults and children weighing more than 40 kg are usually prescribed inside after eating 1 tablet (250 mg) once a day.
Infections of the skin
Recommended duration of treatment:
Dermatomycosis of the foot (interdigital, plantar or as a socks): 2-6 weeks.
Dermatomycosis of the trunk, legs: 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. With onychomycosis, brushes in most cases are sufficient for 6 weeks of treatment. In the onychomycosis of 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 time period that is necessary for the growth of a healthy nail.
Application in the elderly
There is no reason to assume that for elderly people, it is required to change the dosage regimen of the drug or that they have side effects that differ from those in younger patients. 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 EFFECT
Terbifin В® is generally well tolerated. Side effects are usually mild or moderate and are transient. Below are the undesirable phenomena that were observed during clinical trials or after the drug was released to the market.
When assessing the incidence of side effects, the following grades are used: "very often" (V 1/10), "often" (from V 1/100 <1/10), "sometimes" (V 1/1000 <1/100), "Rarely" (V 1/10000 <1/1000), "very rare" (V 1/10000), including isolated messages.
From the hemopoietic system: very rarely - neutropenia, agranulocytosis, thrombocytopenia, increased activity of "liver" transaminases, lymphopenia.
From the immune system: very rarely - anaphylactoid reactions (including angioedema), cutaneous and systemic lupus erythematosus.
From the nervous system: often - headache; sometimes - a violation of taste, including their loss, usually the recovery occurs within a few weeks after discontinuation of treatment). There are separate reports of cases of long-term disturbances of taste sensations. In some cases, while taking the drug, a decrease in food intake was noted, which led to a significant reduction in weight.
On the part of the liver: rarely - hepatobiliary dysfunction (predominantly of the cholestatic nature), including very rare cases of severe hepatic insufficiency (some with fatal outcome or requiring liver transplantation).
From the gastrointestinal tract: very often - a feeling of overflow of the stomach, loss of appetite, indigestion, nausea. Slight abdominal pain, diarrhea.
From the skin and subcutaneous tissue: very often - not severe skin reactions (rash, urticaria), very rarely - serious skin reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis); psoriasis-like rashes on the skin or exacerbation of psoriasis. Very rarely there were cases of hair loss, although the cause-and-effect relationship of this phenomenon with taking the drug is not established.
In the event that a progressive skin rash develops, treatment with Terbifin should be discontinued.
From the musculoskeletal system: very often - arthralgia, myalgia.
Other: very rarely - a feeling of fatigue.
CONTRAINDICATIONS
- children with body weight less than 40 kg;
- chronic or active liver disease;
- severe renal failure (CC less than 50 ml / min);
severe hepatic impairment;
- Hypersensitivity to terbinafine or any other component that is part of the drug.
With caution: with kidney failure, alcoholism, oppression of bone marrow hematopoiesis, tumors, metabolic diseases, occlusive diseases of the vessels of the extremities.
It is not recommended to prescribe Terbifin В® to patients with chronic or active liver disease. Before the appointment of Terbifin in tablets, it is necessary to determine whether the patient has previous liver disease. Hepatotoxicity can occur both in patients with previous liver diseases, and without them. Patients who are prescribed Terbifin В® should be warned that it is necessary to immediately inform the attending physician of the appearance of symptoms such as persistent nausea, lack of appetite, 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.
PREGNANCY AND LACTATION
The data of experimental studies do not give grounds to assume the presence of undesirable phenomena with respect to fertility and toxic effects on the fetus. Since the clinical experience with the use of Terbifin В® in pregnant women is very limited, the drug should not be used during pregnancy, unless the expected benefit from therapy exceeds the potential risk.
Terbinafine is excreted in breast milk, so women who receive Terbifin В® inside should not breast-feed.
APPLICATION FOR FUNCTIONS OF THE LIVER
Carefully with renal failure.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in chronic or active liver disease, with severe hepatic insufficiency.
Before the appointment of Terbifin in tablets, it is necessary to determine whether the patient has previous liver disease. Hepatotoxicity can occur both in patients with previous liver diseases, and without them. Patients who are prescribed Terbifin В® should be warned that it is necessary to immediately inform the attending physician of the appearance of symptoms such as persistent nausea, lack of appetite, 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.
APPLICATION FOR CHILDREN
Contraindicated in children weighing up to 40 kg.
APPLICATION IN ELDERLY PATIENTS
There is no reason to assume that for elderly people, it is required to change the dosage regimen of the drug or that they have side effects that differ from those in younger patients. 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.
SPECIAL INSTRUCTIONS
It has been shown that terbinafine inhibits metabolism mediated by the enzyme 2D6 (CYP2D6). Therefore, continuous monitoring of patients receiving concomitantly metabolized with terbifin В® with this enzyme (such as tricyclic antidepressants, beta-adrenoblockers, selective serotonin reuptake inhibitors, class 1C antiarrhythmics, and monoamine oxidase B type inhibitors) should be performed in case the drug used simultaneously has a small range of therapeutic concentration.
Irregular application or early termination of treatment increases the risk of relapse. If after 2 weeks of treatment there is no improvement, it is necessary to re-determine the causative agent of the disease and its sensitivity to the drug.
Before and during the treatment, monitoring of liver function parameters is necessary.
In the process of treatment, it is necessary to follow the general rules of hygiene to prevent reinfection (through / underwear, shoes).
Impact on the ability to drive vehicles and manage mechanisms
Data on the effect of Terbifin В® on the ability to drive a car and control mechanisms are absent.
OVERDOSE
There are reports of several cases of overdose (the accepted dose of the drug was up to 5 g), with headache, nausea, epigastric pain and dizziness.
The recommended treatment in case of an overdose treatment includes an activity to remove the drug, primarily by prescribing activated charcoal and washing the stomach; if necessary, conduct symptomatic and supportive therapy.
DRUG 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 simultaneous application of the above mentioned preparations and Terbifin В® is required, an appropriate 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%.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
The results of studies conducted in vitro and in healthy volunteers show that terbinafine has little potential to suppress or enhance the clearance of most drugs that are metabolized by the cytochrome P450 system (eg, terfenadine, triazolam, tolbutamide or oral contraceptives) which are metabolized with the participation of CYP2D6.Terbinafine does not affect the clearance of the antipyrine or digoxin. There have been reports of several cases of menstrual irregularity in patients taking Terbifin В®together with oral contraceptives, although the frequency of these disorders does not exceed the average frequency of such disorders in patients taking only oral contraceptives.
Terbinafine can enhance the effect of caffeine or increase its concentration in the plasma. Terbinafine reduces caffeine clearance by 20%. In vivo and in vitro studies, terbinafine has been shown to inhibit metabolism mediated by the 2D6 enzyme (CYP2D6). These data can be clinically significant for those drugs that are metabolized primarily by this enzyme: tricyclic antidepressants, beta-adrenoblockers. Selective serotonin reuptake inhibitors, class 1C antiarrhythmics and type B monoamine oxidase inhibitors, if the concomitant drug has a small range of therapeutic concentration. Terbinafine reduces the clearance of desipramine by 82%.
Ethanol and other hepatotoxic drugs increase the risk of hepatotoxicity.
Terbinafine can weaken the action of cyclosporine and reduce its concentration in the plasma. Terbinafine increases the clearance of cyclosporine by 15%.
TERMS OF RELEASE FROM PHARMACY
On prescription.
TERMS AND CONDITIONS OF STORAGE
Store in a dark place at a temperature of no higher than 25 В° C. Keep out of the reach of children. Shelf life - 3 years.
