Instructions for Terbinafine
Composition per 1 tablet: active substance: terbinafine hydrochloride (in terms of terbinafine) - 281.0 mg (250 mg); excipients: lactose monohydrate (milk sugar) 86 mg; hydroxypropyl cellulose 3.6 mg; potato starch 28.4 mg; croscarmellose sodium 8.4 mg; talcum powder 8.4 mg; magnesium stearate 4.2 mg.
Terbinafine is allylamine, which has a wide spectrum of action against fungi that cause diseases of the skin, hair and nails, including dermatophytes (Trychophyton rubrum, Trychophyton mentagrophytes, Trychophyton verrucosum, Trychophyton violaceum, Trychophyton tonsurans, Microsporum canis, Epidermophyton floc also yeast of the genus Candida (e.g. C. albicans) and Pityrosporum. In low concentrations, terbinafine has a fungicidal effect against dermatophytes, molds, and some dimorphic fungi.
Activity against yeast fungi, depending on their type, can be fungicidal or fungistatic. Terbinafine, inhibiting squalene epoxidase in the cell membrane of the fungus (not related to the cytochrome P450 system), specifically inhibits the early stage of sterol synthesis in the fungal cell, which leads to ergosterol deficiency, intracellular accumulation of squalene and death of the fungal cell.
When terbinafine is used orally in the skin, hair and nails, drug concentrations are created that provide a fungicidal effect. Pharmacokinetics After oral administration, terbinafine is well absorbed (more than 70%); the absolute bioavailability of terbinafine due to the “first pass” effect is approximately 50%.
After a single oral administration of terbinafine at a dose of 250 mg, its maximum plasma concentration (Cmax) is reached after 1.5 hours and is 1.3 μg / ml.
With the constant intake of terbinafine, its Cmax increased on average by 25% more, compared with a single dose; the area under the concentration-time curve (AUC) increased 2.3 times. Based on the increase in AUC, the effective half-life (30 hours) can be calculated.
Eating to a moderate extent affects the bioavailability of the drug (AUC increases by less than 20%), therefore, dose adjustment of terbinafine is not required when taken with food. Terbinafine largely binds to plasma proteins (99%). It quickly penetrates the dermal layer of the skin and concentrates in the lipophilic stratum corneum. Terbinafine also penetrates 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.
Terbinafine has also been shown to penetrate the nail plates in the first few weeks after starting therapy. Terbinafine is metabolized rapidly and substantially with the participation of at least seven isoenzymes of cytochrome P450, with the main role played by the isoenzymes CYP2C9, CYP1A2, CYP3A4, CYP2C8 and CYP2C19.
As a result of terbinafine biotransformation, metabolites are formed that do not have antifungal activity and are excreted mainly by the kidneys.
Repeated use of terbinafine, leading to an increase in its concentration in the blood serum, is accompanied by a three-phase excretion with a final half-life of about 16.5 days. No changes in the equilibrium concentration of terbinafine in plasma depending on age.
In pharmacokinetic studies of a single dose of Terbinafine Tablets 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 shown.
Terbinafine Side Effects:
Terbinafine Tablets is generally well tolerated. Side effects are usually mild or moderate and are transient. The frequency of side effects was evaluated 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 cannot be estimated based on available data).
Disorders from the blood and lymphatic system: infrequently - anemia; very rarely - neutropenia, agranulocytosis, pancytopenia, thrombocytopenia. Immune system disorders: very rarely - anaphylactoid reactions (including angioedema), skin and systemic lupus erythematosus (or their exacerbation), the frequency is unknown - anaphylactic reactions, a syndrome similar to serum sickness.
Mental disorders: often - depression; infrequently - anxiety. Disorders from the nervous system: very often - headache; often - dizziness, taste disturbances, up to their loss (usually recovery occurs within a few weeks after stopping treatment), infrequently - paresthesia, hypesthesia; frequency unknown - loss of smell, including for a long period of time, decrease in smell.
Violations of the organ of vision: infrequently - impaired vision; frequency unknown - blurred vision, decreased visual acuity. Hearing disorders and labyrinth disorders: infrequently - tinnitus; frequency unknown - hearing loss, hearing impairment. Disorders from the vessels: the frequency is unknown - vasculitis. Disorders from the gastrointestinal tract: very often - bloating, decreased appetite, dyspepsia, nausea, mild abdominal pain, diarrhea, the frequency is unknown - pancreatitis. Disorders from the liver and biliary tract: rarely
- hepatobiliary dysfunction (mainly of a cholestatic nature), including liver failure, including rare cases of severe liver failure (some fatal or requiring liver transplantation);
hepatitis, jaundice, cholestasis, increased activity of “liver” transaminases.
In most cases, when liver failure developed, patients had serious concomitant systemic diseases and the causal relationship of liver failure with Terbinafine Tablets was doubtful;
Disorders of the skin and subcutaneous tissue: very often
- rash, urticaria, infrequently
- photosensitivity reactions; rarely
- Stevens-Johnson syndrome, toxic epidermal necrolysis; acute generalized exanthematous pustulosis, erythema multiforme, toxic skin rash, exfoliative dermatitis, bullous dermatitis, psoriasis-like rashes or exacerbation of psoriasis, alopecia; unknown frequency
- A drug rash with eosinophilia and systemic symptoms (rash, swelling, fever, and swollen lymph nodes).
Disorders from the musculoskeletal and connective tissue: very often - arthralgia, myalgia, frequency unknown - rhabdomyolysis.
Common disorders: often - a feeling of fatigue, infrequently - an increase in body temperature, the frequency is unknown - a flu-like syndrome. Laboratory and instrumental data: infrequently - weight loss (secondary to impaired taste), frequency unknown - increased activity of creatine phosphokinase.
If any of the side effects indicated in the instructions are exacerbated, or if you notice any other side effects not listed in the instructions, inform your doctor.
Special conditions Terbinafine:
Irregular use or early termination of treatment will attempt to risk a relapse. Before starting the use of terbinafine in tablets, an analysis of liver function is necessary. Hepatotoxicity can occur in patients with previous liver disease, 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 who are prescribed the drug should be warned that they should immediately inform the attending physician about the occurrence of symptoms of persistent nausea, loss of appetite, feeling tired, vomiting, pain in the right hypochondrium, jaundice, dark urine or light stool . In the event of the 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 eosiophilia and systemic symptoms) were extremely rare with the use of Terbinafine Tablets.
When using the drug in tablets, extremely rare changes in the cellular composition of cropi were observed (neutropenia. Agranulocytosis, thrombocytopenia, pancytopenia).
In the case of the development of qualitative or quantitative changes on the part of blood cells, the cause of the disorders should be established and the question of reducing the dose of the drug or, if necessary, stopping the drug therapy should be considered. ''
Herbinafine inhibits the metabolism mediated by the enzyme 2D6 (CYP2D6), therefore, it is necessary to constantly monitor patients receiving, along with terbinafine, treatment with drugs predominantly metabolized with this enzyme (such as tricyclic antidepressants, bsta-blockers, selective serotonin reuptake inhibitors, anti class 1C and monoamine oxidase type B inhibitors)
if the drug used simultaneously has a small range of therapeutic concentration. Effect on the ability to drive vehicles and mechanisms: The effect of the drug on the ability to drive vehicles and work with mechanisms has not been studied.
When dizziness develops with drug therapy, patients should not drive vehicles
Mycoses caused by microorganisms sensitive to Terbinafine Tablets: - onychomycosis caused by dermatophytes; - mycoses of the scalp; - fungal infections of the skin - treatment of dermatomycosis of the trunk, legs, feet, as well as yeast infections of the skin caused by fungi of the genus Candida (for example, Candida albicans)
- in cases where the localization, severity or prevalence of infection determines the feasibility of oral therapy.
Contraindications hypersensitivity to terbinafine or to any other component of the drug; - children's age up to 3 years, with a body weight of less than 20 kg (there is no data on the use); - severe, chronic or active liver disease; - impaired renal function (creatinine clearance less than 50 ml / min or serum creatinine concentration more than 300 μmol / l), because the use of the drug in this category of patients is not well understood; - lactose intolerance, lactase deficiency and glucose-galactose malabsorption.
With caution. If you have one of these diseases, be sure to consult your doctor before using the drug. When using the drug, caution should be exercised in patients with impaired liver function.
Caution must be exercised when using the drug in patients with inhibition of bone marrow hematopoiesis, cutaneous lupus erythematosus, or systemic lupus erythematosus.
The drug should be used with caution in patients with concomitant diseases such as psoriasis or lupus erythematosus due to the possible exacerbation of these diseases.
Pregnancy and lactation Clinical experience with the use of terbinafine in pregnant women is limited, so the drug should not be used during pregnancy, unless the expected benefit to the mother from the therapy outweighs the potential risk to the fetus.
Terbinafine is excreted in breast milk, so the drug is contraindicated during breastfeeding.
Drug Interactions Terbinafine:
The effect of other drugs on terbinafine Plasma clearance of terbinafine can be accelerated under the influence of drugs - metabolic inducers, and suppressed under the influence of cytochrome P450 inhibitors.
If necessary, the simultaneous use of the above drugs and Terbinafine Tablets may require appropriate correction of the dosage regimen of the latter.
Cimetidine can enhance the action of terbinafine or increase its concentration in plasma. Cimetidine reduces terbinafine clearance by 33%. Fluconazole increases Cmax and AUC of terbinafine by 52% and 69%, respectively, due to inhibition of the isoenzyme CYP2C9 and CYP3A4.
A similar increase in the exposure of Terbinafine Tablets can occur with the use of other drugs that inhibit the CYP2C9 and CYP3A4 isoenzymes, for example, ketoconazole and amiodarone. Rifampicin can weaken the action of terbinafine or reduce its concentration in plasma. Rifampicin increases terbinafine clearance by 100%. The effect of terbinafine on other drugs
Terbinafine inhibits the metabolism mediated by the isoenzyme 2D6 (CYP2D6). These data may turn out to be clinically significant for those drugs that are metabolized primarily by this enzyme: tricyclic antidepressants, beta-blockers, selective serotonin reuptake inhibitors, antiarrhythmic drugs (class 1A, 1B and 1C) and monoamine oxidase inhibitors
In type, - if the drug used simultaneously has a small range of therapeutic concentration. Terbinafine Tablets reduces desipramine clearance by 82%.
In studies on healthy volunteers with an active metabolism of dextrofetorphan (an antitussive and a CYP2D6 substrate), terbinafine increased the metabolic coefficient of dextromethorphan / dextrorphan in urine by 16-97 times. Thus, terbinafine in individuals with high activity of the CYP2D6 isoenzyme can reduce the activity of the latter. Terbinafine reduces the clearance of caffeine when administered intravenously by 19%.
Drug interactions that do not have or have little effect Terbinafine has little potential to suppress or enhance the clearance of most drugs that are metabolized by the P450 cytochrome system (e.g. terfenadine, triazolam, tolbutamide or oral contraceptives), except for those metabolized by CYP2D6 . Terbinafine does not affect the clearance of phenazone or digoxin.
Terbinafine does not significantly affect the pharmacokinetics of fluconazole. There were no clinically significant interactions between terbinafine and the components of co-trimoxazole (trimethoprim and sulfamethoxazole), zidovudine, or theophylline. With the simultaneous administration of Terbinafine Tablets with oral contraceptives, a menstrual cycle is possible.
Terbinafine may decrease the concentration in the blood serum or the severity of the clinical effects of the following drugs. Terbinafine increases the clearance of cyclosporine by 15%.
Interaction with food and drinks Food slightly affects the bioavailability of terbinafine (increase in AUC <20%), which does not require a change in the dose of the drug.
The drug is taken orally, regardless of food intake, washed down 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 disease. Adults 250 mg 1 time per day. Infections of the skin Recommended treatment duration: foot dermatomycosis (interdigital, plantar or sock type) - 2-6 weeks; dermatomycosis of the trunk, lower legs - 2-4 weeks; skin candidiasis - 2-4 weeks.
The complete disappearance of the manifestations of infection and complaints associated with it can occur no earlier than a few weeks after mycological cure. Infections of hair and scalp
Recommended duration of treatment: scalp mycosis - 4 weeks. Mycosis of the scalp is observed mainly in children. Onychomycosis The duration of treatment in most patients is from 6 to 12 weeks.
With onychomycosis of the hands in most cases, 6 weeks of treatment are sufficient. With onychomycosis of the feet in most cases, 12 weeks of treatment is sufficient. Some patients who have a reduced nail growth rate may require longer treatment.
The optimal clinical effect is observed several months after mycological cure and cessation of therapy. This is determined by the period of time that is necessary for the growth of a healthy nail. Use in children There are no data on the use of the drug in children under the age of 3 years (whose body weight is usually less than 12 kg).
The use of the drug for treatment in children with body weight less than 20 kg is not recommended in view of the impossibility of an adequate dose selection. The use in children from 3 to 12 years old 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.
The duration of treatment and the dose depend on the body weight of the child. In children older than 3 years of age, the drug is prescribed 1 time per day. A 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 elderly patients need to change the dosage regimen of the drug or that they have side effects that differ from those in younger patients.
In the case of the use of the drug in tablets in this age group, the possibility of concomitant impaired liver or kidney function should be considered.
Overdose Symptoms Terbinafine:
epigastric pain and dizziness.
Recommended in case of overdose, treatment includes measures to remove the drug, primarily by prescribing activated carbon and gastric lavage; if necessary, carry out symptomatic and supportive therapy.