1 tablet contains terbinafina (hydrochloride) 250 mg
other ingredients:cellulose microcrystalline, starch maize, silica colloidal anhydrous, hypromellose, talc, magnesium stearate.The
basic physico-chemical properties:round flat tablets from white to yellowish-white.The
Antifungal drugs for use in dermatology. Antifungal drugs for systemic use. Terbinafine.
ATC Code D01B A02.The
Terbinafine is allylamine, which is a broad spectrum antifungal activity in infections of the skin, hair and nails caused by dermatophytes such asTrichophyton(e.g.T. rubrum, T. mentagrophytes, T. verrucosum, T. tonsurans, T. violaceum), Microsporum(e.g.Microsporum canis), Epidermophyton floccosumand yeast fungi of the genusCandida(e.g.Candida albicans) andPityrosporum. At low concentrations terbinafine has fungicidal action against dermatophytes, molds and certain dimorphic fungi. Activity against yeasts, depending on their type, may be fungicidal or fungistatic.
Terbinafine specifically promotes early stage of the biosynthesis of sterols in the fungal cell. This leads to a deficiency of ergosterol and to an intracellular accumulation of squalene, which causes the death of the fungus cell. The action of terbinafine by inhibiting the enzyme skvalenepoksidazu in the cell membrane of the fungus. This enzyme does not belong to the cytochrome P450.
when ingestion, the drug accumulates in the skin in concentrations that ensure the fungicidal effect of the drug.
After taking the terbinafine is well absorbed (> 70%); the bioavailability of terbinafine is the result of first-pass metabolism is approximately 50%. A single oral dose of 250 mg of terbinafine showed an average value of maximum concentrations in blood plasma - 1.30 mg/ml 1.5 hours after taking the drug. In the equilibrium state compared to a single dose, the maximum concentration of terbinafine was on average 25% higher, and the plasma AUC increased 2.3 times. The effective half-life (~ 30 hours) can be calculated on the basis of increasing the plasma AUC. The meal has a mild effect on the bioavailability of terbinafine (an increase in AUC by at least 20%), but not enough to require dose adjustment.
Terbinafine binds strongly to plasma proteins. It diffuses rapidly through the dermis and concentrates in the lipophilic stratum corneum.
Terbinafin also excels with the secret of the skin glands and thus reaches high concentrations in the hair follicles, hair and skin. It is also proved that terbinafine is distributed in the nail plates during the first weeks after the start of therapy. Terbinafine is metabolized rapidly and extensively with the participation of at least seven CYP isoenzymes with significant contributions from CYP2C9, CYP1A2, CYP3A4, CYP2C8 and CYP2C19. As a result of biotransformation terbinafina metabolites are formed, which do not have antifungal activity and are excreted mainly in the urine. The half-life period is 17 hours. Evidence of accumulation of drug in the body was not.
changes in the pharmacokinetics of the drug, depending on the age of the patient is not observed, but the rate of withdrawal of the drug from the body may be reduced in patients with impaired renal or liver function, which leads to increased levels of terbinafina in the blood.
the Bioavailability of terbinafine is not dependent on food intake.
studies of pharmacokinetics of single doses of the drug involving patients with renal impairment (creatinine clearance
Fungal infections of the skin and nails caused byTrichophyton(e.g.T. rubrum, T. mentagrophytes, T. verrucosum, T. violaceum),Microsporum canisandEpidermophyton floccosum:The
Hypersensitivity to terbinafine or any of the excipients of the drug.The
the Influence of other medicinal products on terbinafine
Clearance of terbinafine in plasma can be elevated by drugs that induce the metabolism, and can be reduced by drugs which inhibit cytochrome P450. If necessary, concomitant treatment with such drugs dosing Terminara need to adjust accordingly.
Drugs that may increase the effect or plasma concentrations of terbinafine
Cimetidine decreased the clearance of terbinafine by 30%.
fluconazole increased the indices Cmaxand AUC of terbinafine by 52% and 69%, respectively, due to inhibition of enzymes CYP2C9 and CYP3A4. The same increase is possible with the simultaneous application terbinafina drugs that inhibit CYP2C9 and CYP3A4, such as ketoconazole and amiodarone.
Drugs that may reduce the effect or plasma concentrations of terbinafine
Rifampicin increased the clearance of terbinafine by 100%.
the Effect of terbinafine on other drugs
Research conductedin vitrowith the participation of healthy volunteers show that terbinafine has little capacity to suppress or enhance the clearance of drugs metabolized with participation of cytochrome P450 (e.g. terfenadine, triazolam, tolbutamide or oral contraceptives), with the exception of those drugs that are metabolized with the participation of CYP2D6.
Terbinafin does not affect the clearance of antipyrine or digoxin.
No effect of terbinafine on the pharmacokinetics of fluconazole has not been observed. Besides, there has not been a clinically significant interaction between terbinafine and the concomitant used drugs with a possible interaction potential such as co-trimoxazole (trimethoprim and sulfamethoxazole), zidovudine or theophylline.
Reported cases of menstrual disorders (intermenstrual bleeding or irregular menstrual cycle) in patients taking terbinafine at the same time with oral contraceptives, although the frequency of these disorders remains within the frequency of adverse reactions in patients receiving only oral contraceptives.
Drugs whose effect or plasma concentrations may increase terbinafin
Terbinafin reduced the clearance of caffeine, which was administered intravenously, by 21%.
Studiesin vitroandin vivoin which it was found that terbinafine inhibits CYP2D6 - mediated metabolism. These data may be clinically important for patients receiving drugs that are metabolized with the participation of CYP2D6, such as tricyclic antidepressants (TCAs), beta-blockers, selective inhibitors of serotonin reuptake (SSRIs), antiarrhythmics (including class 1A, 1B and 1C) and monoamine oxidase inhibitors (MAO-Is) type B, in the case where a drug that is used is small in the range of therapeutic concentrations.
Terbinafin reduced the clearance of desipramine by 82%.
the use of terbinafina can lead to changes in the status of rapid metabolizers CYP2D6 status of slow metabolizers.
Drugs whose effect or plasma concentrations may reduce terbinafin
Terbinafine increased the clearance of cyclosporine by 15%.
Combinorm tablets is not recommended in patients with chronic or active liver disease. Before prescribing terbinafine tablets you need to evaluate all pre-existing liver disease.
Hepatotoxicity is possible in patients with and without prior liver disease, so periodic monitoring of liver function is recommended (after 4-6 weeks of treatment). The use of the drug Combinorm should be immediately discontinued in case of increased activity of the indicators of liver function tests.
Patients receiving Combinorm should warn that you should immediately inform your doctor about any signs or symptoms indicating liver dysfunction such as pruritus, unexplained constant nausea, loss of appetite, anorexia, jaundice, vomiting, increased fatigue, right-sided pain in the upper abdomen or dark urine or discolored feces. Patients with these symptoms should discontinue use of inside of terbinafine and liver function the patient should be immediately assessed.
in the application of the drug reported taste impairment and loss of taste. This can lead to poor appetite, loss of body weight, anxiety and depressive symptoms. If there are symptoms of taste disorders, the drug should be stopped.
breaking the sense of smell
it was Also reported on violations and loss of smell. These disorders may disappear after discontinuation of therapy, but may also be prolonged (more than 1 year) or permanent. If there is a violation of smell, the drug should be stopped.
depressive symptoms may occur during treatment, which may require treatment.
serious skin reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis) have rarely been reported. In case of progressive lesions on the skin treatment terbinafine tablets should be discontinued.
Combinorm should be used with caution in patients with psoriasis, because there have been reports of very rare cases of exacerbation of psoriasis.
pathological changes from blood (neutropenia, agranulocytosis, thrombocytopenia, pancytopenia) were reported very rarely. It is necessary to assess the cause of any pathological change from the blood in patients and consider the possible change in treatment regimen, including discontinuation of treatment with the drug.
the use of Terbinormu in tablets in patients with impaired renal function (creatinine clearance of less than 50 ml/min or serum creatinine level of more than 300 µmol/l) has not been properly studied and is therefore not recommended.
Combinorm should be used with caution to patients with lupus erythematosus, as there have been reports of very rare cases of exacerbation of lupus.
use during pregnancy or lactation.
experience with the use of terbinafine tablets in pregnant women is very limited, so it should not be used during pregnancy, except in cases when the clinical condition of the woman requires treatment with oral terbinafine and the expected benefit to the pregnant woman exceeds any potential risk to the fetus.
do Not use Combinorm in the period of breast-feeding, as terbinafine is excreted in the milk.
Ability to influence the reaction rate when driving motor transport or operating other mechanisms.
there is no Data on the influence of the turbine On the ability to drive vehicles and operate machinery. Patients who have dizziness as an undesirable reaction to the use of the drug should avoid driving and working with other mechanisms.
the Drug is designed for oral use.
Adults: 1 tablet (250 mg) 1 times a day.
The duration of treatment depends on the nature and severity of the disease.
the recommended duration of treatment:The
the complete disappearance of symptoms of infection can occur only a few weeks after detection of the absence of pathogens by laboratory control.
the Duration of treatment for most patients is between 6 weeks to 3 months. Treatment periods shorter than 3 months possible for patients with lesions of the nails on the fingers, Polish on the toes, except the big toe, or patients of younger age. In the treatment of nail lesions on the toes is usually enough 3 months, although some patients may require treatment lasting 6 months or longer. Patients who need a longer treatment, determine the reduced rate of nail growth during the first weeks of treatment.
the complete disappearance of symptoms of infection can occur only a few weeks after detection of the absence of pathogens by laboratory control.
patients with hepatic impairment
Combinorm tablets is not recommended in patients with chronic or active liver disease.
patients with renal impairment
Use Terminara tablets in patients with impaired renal function has not been adequately studied and therefore not recommended for this group of patients.
there is no Evidence that older patients need to change the dose of the drug or that they have adverse reactions that differ from those in younger patients. In this age group, the use of the drug should take into account the possibility of impaired liver or kidney function.
data on the use of the drug in children is limited, so its use is not recommended for this age group of patients.
Symptoms: headache, nausea, epigastric pain and dizziness.
Treatment: withdrawal of the drug using activated charcoal and, if necessary, symptomatic maintenance therapy.
the following classification is used to estimate the incidence of different adverse reactions: 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 (cannot be set based on available data).
by blood and lymphatic system
neutropenia, agranulocytosis, thrombocytopenia are Very rare.
the Frequency is not known: anaemia, pancytopenia.
by the immune system
Very rarely anaphylactoid reactions (including angioedema), cutaneous and systemic lupus erythematosus.
Frequency unknown: anaphylactic reactions, such as symptoms of serum sickness.
from metabolism and nutrition
Very common: decreased appetite.
the Frequency is unknown: anxiety and depressive symptoms secondary to disorders of taste.
from nervous system
Often a headache.
Rarely: breach of taste sensations, including loss of taste is usually restored a few weeks after discontinuation of the drug. Very rarely reported prolonged taste disturbance, which sometimes leads to a decrease in food consumption and a significant loss of body weight.
rarely paresthesia, hypesthesia, dizziness.
frequency unknown: anosmia, including permanent anosmia, hyposmia.
on the part of the hearing and vestibular apparatus
vertigo is Very rare.
unknown Frequency: hearing loss, hearing impairment, noise in the ears.
Frequency not known: vasculitis.
from the digestive system
Very common: gastrointestinal symptoms (feeling of fullness of stomach, indigestion, nausea, abdominal pain, diarrhea).
Frequency unknown: pancreatitis.
on the part of the liver and biliary tract
Rarely do serious liver disorders, including hepatic insufficiency, increased liver enzyme levels, jaundice, cholestasis, and hepatitis occur. If there is a violation of liver function, treatment must be stopped. Very rarely have there been reports of serious liver failure (some fatal cases or cases requiring a liver transplant).
on the part of the skin and subcutaneous tissue
Very often less serious forms of skin reactions (rash, hives).
Very rarely serious skin reactions (e.g. erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis) photosensitivity (e.g. photodermatosis, photosensitivity reaction and polymorphic photodermatosis) alopecia.
frequency unknown: psoriasis-like rash or exacerbation of psoriasis. Serious skin reactions (e.g. acute generalized exanthematous pustules).
from the musculoskeletal system and connective tissue
very often reactions from the musculoskeletal system (arthralgia, myalgia).
Frequency unknown: rhabdomyolysis.
Frequency unknown: fever, flu-like illness, pyrexia.
Frequency unknown: increased CPK blood.The
Store at a temperature not exceeding 25 ° C, out of reach of children.The
7 tablets per blister, 2 blisters in a cardboard box.The
According to the recipe.The
WORLD Medicine LTD/WORLD MEDICINE LTD.The
CA SLAVIA PHARM S. R. L., Romania/SC SLAVIA PHARM SRL, Romania.
the Boulevard Theodore Pallada No. 44, sector 3, 032266, Bucharest/Boulevard Theodor Pallady No. 44 C, sector 3, 032266, Bucharest.
"Terzhinan" refers to a group of antimicrobial and antiseptic agents that are used in gynecology. The drug is prescribed by the doctor after detection:
the Preparation can be used only after consulting a doctor, independent use is ineffective and dangerous. The appearance of the medicine: light-yellow tablets for local use. Perhaps the presence of lighter or darker inclusions, form-flat, on both sides of the drug printed letter "T".
in addition to bacterial infections, the drug may be used prior to gynecological surgery or immediately prior to delivery, medical abortion, intrauterine device and after the procedure. "Terzian" prevents infection with diathermocoagulation and hysterography.