Carbamazepine таб 200 mg No. 50

General characteristics. Structure:

Active agent: carbamazepine of 200 mg;
excipients: potato starch, silicon dioxide colloid (aerosil), povidone low-molecular (polyvinylpirrolidone low-molecular medical), polisorbat-80 (twin-80), talc, magnesium stearate.
Description: Tablets of color, white or white with a yellowish shade, ploskotsilind-richesky with risky and a facet.

Pharmacological properties:

Pharmacodynamics. Anticonvulsant drug, derivative tricyclic iminostilbene. Anticonvulsant action is connected with decline in the ability of neurons to support the high frequency of development of repeated action potentials by means of an inactivation of natrium channels. Also carbamazepine has moderate anti-maniacal, antipsychotic effect, and also analgeziruyushchy action at neurogenic pains. Receptors of piperidic acid which are tied with calcium channels are involved in the mechanism of effect of drug, and also influence of carbamazepine on systems of modulators of neurotransfer matters. Antidiuretic effect of carbamazepine is connected with hypothalamic influence on osmoreceptors which is mediated through secretion of antidiuretic hormone, and also direct action on renal tubules.

Pharmacokinetics. After intake carbamazepine is absorbed almost completely. The maximum concentration is reached in 12 hours at a single dose. Linkng with proteins of a blood plasma makes 70-80% - at adults, 55-59% - at children. Equilibrium concentration of drug in plasma are reached in 1-2 weeks (speed of achievement depends on specific features of metabolism: an autoinduktion of fermental systems of a liver, heteroinduction by another, at the same time applied medicines), and also from a condition of the patient, a dose of drug and duration of treatment. Essential interindividual distinctions of values  of equilibrium concentration in the therapeutic range are observed: at most of patients these values fluctuate from 4 to 12 mkg/ml (17-50 µmol/l).
Concentration of carbamazepine-10,11-epoxide (pharmacological an active metabolite) make about 30% of concentration of carbamazepine. Communication with proteins of plasma children - 55-59%, at adults have 70-80%. Drug gets through a placental barrier. Concentration in breast milk makes 25-60% of concentration it in plasma. It is metabolized in a liver, it is preferential on an epoxy way with formation of the main metabolites: active-carbamazepine-10-11-epoxide and an inactive conjugate with glucuronic acid. Concentration of carbamazepine - 10,11 epoxides makes 30% of concentration of carbamazepine. An elimination half-life after reception of a single peroral dose - 25-65 h ( on average about 36 h), after repeated reception depending on treatment duration - 12-24 h (owing to an autoinduktion of monooksigenazny system of a liver). At children, owing to more bystry elimination of carbamazepine, use of higher doses of drug at the rate on body weight kg, in comparison with adults can be required.

Indications to use:

Carbamazepine is applied to treatment of epilepsy (big and small attacks, the mixed epilepsy forms, focal epilepsy, local forms of a posttraumatic and postencephalitic origin, an epileptiform neuralgia; prevention of faznoprotekayushchy effective disturbances (maniac-depressive psychosis and other psychotic frustration of mood).

Route of administration and doses:

Drug is appointed to adults and children. Carbamazepine is accepted inside in time or after food, washing down with a small amount of liquid. At treatment of epilepsy when it is possible, carbamazepine is applied in the form of monotherapy. The adult treatment there begin with appointment on 0,1 - 0.2 g 1-2 times a day. Further the dose is gradually increased before achievement optimum acting which usually makes 0,4 g 2-4 times a day. For children the average daily dose is defined at the rate of 10-20 mg/kg   of body weight a day and makes: for children at the age of 4-12 month - 0,1 - 0,2 g a day, from 1 year to 5 years -   0,2-0,4 g, from 5 to 10 years - 0,4-0,6 g, from 10 to 15 years 0,6-1,0 g divide a daily dose into several receptions. At treatment of an epileptiform neuralgia the initial dose makes 0,2-0,4 g a day, then the dose is gradually raised, if necessary to 0,6-0,8 g in stages. After disappearance of pain the dose is gradually reduced to 0,2 g a day. For prevention of affective disturbances in the first week the daily dose makes 0.2-0,4 g. In the subsequent the dose is increased by 1 tablet a week, bringing it to 1 g. The daily dose is divided evenly into 3-4 receptions. Duration of treatment is established individually.

Features of use:

Monotherapy of epilepsy is begun with purpose of small doses, individually raising them to achievement of desirable therapeutic effect. It is reasonable to define concentration in plasma for the purpose of selection of an optimum dose, in particular at a combination therapy. At transfer of the patient into carbamazepine it is necessary to reduce gradually a dose of earlier appointed antiepileptic means up to its full cancellation. The sudden termination of reception of carbamazepine can provoke epileptic attacks. If it is necessary to interrupt sharply treatment, it is necessary to transfer the patient to other antiepileptic means under cover of the drug shown in such cases (for example the diazepam entered intravenously or rektalno or Phenytoinum entered intravenously). Before purpose of carbamazepine and in the course of treatment the research of function of a liver, especially at patients in whose anamnesis there are data on liver diseases, and also for patients of advanced age is necessary. In case of strengthening of already being available abnormal liver functions or at display of an active disease of a liver, drug should be cancelled immediately. Also before an initiation of treatment it is necessary to conduct a blood picture research (including calculation of thrombocytes, reticulocytes), iron level in blood serum, the general analysis of urine, urea level in blood, the general analysis of urine, urea level in blood, EEG, definition of concentration of electrolytes in blood serum (and periodically during treatment since development of a hyponatremia is possible). Afterwards these indicators should be controlled within the first month of treatment weekly, and then - monthly. Carbamazepine has to be immediately cancelled at the manifestation of reactions of hypersensitivity or symptoms presumably testimonial of development of a syndrome of Stephens-Johnson or a Lyell's disease. Carbamazepine has weak anticholinergic activity, at appointment constant control is necessary for patients with the increased intraocular pressure it. It is necessary to inform patients information on the precursory symptoms of toxicity inherent to probable hematologic disturbances, and also on symptoms from integuments and a liver. The Neprogressiruyushy symptomless leukopenia does not demand cancellation, however, treatment should be stopped at emergence of the progressing leukopenia or the leukopenia which is followed by clinical symptoms of an infectious disease. Before an initiation of treatment it is recommended to conduct ophthalmologic examination. In case of purpose of drug to patients with increase in intraocular pressure, it is necessary to control this indicator constantly. During treatment reaction needs to refrain from occupations potentially dangerous types of activity demanding the increased concentration of attention and speed psychomotor It is recommended to refuse the ethanol use. It is regularly necessary to determine the level of carbamazepine which can be useful in the following situations: at sharp increase in frequency of attacks; to check whether the patient accepts drug properly; during pregnancy; at treatment of children or teenagers; at suspicion on drug absorption disturbances; at suspicion on development of toxic reactions if the patient accepts several medicines.

Side effects:

- From the central nervous system (CNS) and a peripheral nervous system: very often - dizziness, an ataxy, drowsiness, the general weakness; often - a headache, paresis, accommodations; sometimes - the abnormal involuntary movements (for example a tremor, dystonia, tics); nystagmus; seldom - accommodation disturbance, oculomotor disturbances, a dysarthtia, a sonitus, peripheral neuritis, paresthesias, muscular weakness, an agressive behavior, consciousness disturbance.
- From the mental sphere: seldom-gallyushchshatsii (visual or acoustical), depression, appetite loss, concern, agressive behavior, excitement, dezoriyetation; very seldom - activation of psychosis.
 Allergic reactions: often - a small tortoiseshell; sometimes - exfoliative dermatitis, an erythrosis; seldom-volchanochnopodobny syndrome, itch; very seldom - Stephens-Johnson's syndrome, a toxic epidermal necrolysis, photosensitivity, a multiformny and knotty erythema. Seldom - multiorgan reactions of a giperchuvstvitelyyusta of the slowed-down type with the fever, skin rashes, a vasculitis, lymphadenopathy, signs reminding a lymphoma, arthralgias, a leukopenia, an eosinophilia, a gepatosplenomegaliya and the changed indicators of function of a liver (the specified manifestations meet in various combinations).
- From the alimentary system: vomiting, nausea, dryness in a mouth; seldom - increase in activity of serumal transaminases, jaundice, diarrhea, a lock, a loss of appetite, abdominal pains, a glossitis, stomatitis, hepatitis.
- From system of a hemopoiesis: the leukopenia, an eosinophilia, thrombocytopenia are possible; seldom - a leukocytosis, anemia.
- From an urinary system: seldom - renal failures, a renal failure.
- From cardiovascular system (CCC): seldom - disturbances of endocardiac conductivity; decrease or increase in the arterial pressure (AP); very seldom - bradycardia, arrhythmias. AV blockade with faints, a collapse, aggravation or development of chronic heart failure, an exacerbation of coronary heart disease (including emergence or increase of attacks of stenocardia), thrombophlebitis, a thromboembolic syndrome.
- From endocrine system and a metabolism: often - hypostases, a liquid delay, increase in body weight; very seldom - increase in level of L-thyroxine and increase in the TTG level; disturbances of calcium-phosphorus exchange in a bone tissue.
- From a musculoskeletal system: very seldom - an arthralgia, a mialgiya or spasms.
- From sense bodys: very seldom - disturbances of flavoring feelings, a cataract, conjunctivitis; hearing disorder, including sonitus, hyperacusia, gipoakuziya, changes of perception of height of a sound.
- Other: disturbances of a xanthopathy, purple, acne, perspiration, alopecia.

Interaction with other medicines:

P4503A4 (CYP3A4) cytochrome is the main enzyme providing carbamazepine metabolism. Co-administration of a karbamazepip with inhibitors of cytochrome can lead to increase in its concentration in a blood plasma and cause side reactions. Combined use of inductors of cytochrome can lead to carbamazepine metabolism acceleration, decrease in concentration of carbamazepine in a blood plasma and to reduction of therapeutic effect, on the contrary, their cancellation can reduce the speed of biotransformation of carbamazepine and lead to increase in its concentration. Increase concentration of carbamazepine in plasma: verapamil, diltiazem,   фелодипин,   вилоксазин,  the fluoxetine,  Cimetidinum,  niacinamide,   macroleads,  azoles,  inhibitors  of virus protease used at therapy of HIV infection - is required correction of the mode of dosing or monitoring of concentration of carbamazepine in plasma.
Felbamat reduces concentration of carbamazepine in plasma and carbamazepine - 10,11 epoxides, at the same time perhaps simultaneous decrease in concentration in serum of a felbamat increases concentration. Concentration of carbamazepine is reduced: phenobarbital, Phenytoinum, Primidonum, метсуксимид, фенсуксимид, theophylline, rifampicin, Cisplatinum. doxorubicine, it is possible: clonazepam, вальпромид, окскарбазепин and the vegetable drugs containing the St. John's Wort which is made a hole. At combined use of carbamazepine with paracetamol, the risk of toxic influence of the last on a liver increases and its therapeutic activity decreases. MAO inhibitors - increase risk of development of hyperpyrexial crises, hypertensive crises, spasms, death (before purpose of carbamazepine MAO inhibitors cancel at least in 2 weeks). Simultaneous use of carbamazepine with diuretics can lead to the hyponatremia which is followed by clinical manifestations. Carbamazepine accelerates metabolism of indirect anticoagulants, hormonal contraceptives, folic acid, anesthetics; strengthens formation of nefrotoksichny metabolites of a metoksifluran. Strengthens toxic action of an isoniazid.

Contraindications:

Hypersensitivity to carbamazepine or similar medicines in the chemical relation (for example, to tricyclic antidepressants) or to any other component of drug; atrioventricular block; diseases of system of blood, the expressed abnormal liver functions, kidneys, hearts, glaucoma, the first trimester of pregnancy, a lactation: at women of reproductive age carbamazepine has to, whenever possible be applied in the form of monotherapy. Information on a possibility of increase in risk of malformations and an opportunity to undergo antenatal diagnosis has to be provided to patients. Mothers accepting carbamazepine can nurse the children provided that for the child observation concerning development of possible side reactions (drowsiness, allergic skin reactions) will be established.

With care - heavy heart failure, a cultivation hyponatremia (ADG hypersecretion syndrome, a hypopituitarism, a hypothyroidism, insufficiency of bark of adrenal glands), advanced age, active alcoholism (oppression of TsNS amplifies, carbamazepine metabolism), oppression of a marrowy hemopoiesis against the background of reception of medicines (in the anamnesis amplifies); liver failure, chronic renal failure; prostate hyperplasia, increase in intraocular pressure.

Overdose:

At overdose there is strengthening of symptomatology of collateral shows of drug. Symptoms and complaints usually reflect disturbances from TsNS, CCC and respiratory system: TsNS - oppression of the TsNS functions, a disorientation, drowsiness, excitement, hallucinations, a coma; sight misting, muffled speech, dysarthtia, nystagmus, ataxy, dyskinesia, hyperreflexia (in the beginning), hyporeflexia (later); spasms, psychomotor frustration, myoclonus, hypothermia, mydriasis: CCC: tachycardia, decrease in the ABP, sometimes increase in the ABP, disturbance of conductivity with expansion of the QRS complex; faints, cardiac standstill; respiratory system - respiratory depression, a fluid lungs; digestive tract (DT): nausea and vomiting, food passage delay from a stomach, decrease in motility of a large intestine; urinary system: ischuria, oliguria or anury; liquid delay; cultivation hyponatremia. At development of a hyponatremia of cultivation (water intoxication) - restriction of administration of liquids and slow intravenous infusion of 0,9% of solution of sodium of chloride (can sposobstvobat to prevention of edematization of a brain). Carrying out hemosorption on coal sorbents is recommended.

Treatment: The specific antidote is absent. Treatment is based on a clinical condition of the patient; hospitalization, definition of concentration of carbamazepine in plasma (for confirmation of poisoning with this means and assessment of extent of overdose), evacuation of contents of a stomach, a gastric lavage, purpose of absorbent carbon is shown.

Storage conditions:

List B. In the dry place protected from light at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 3 years. Not to use after the date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets on 200 mg On 10 tablets in a blister strip packaging. On 50 tablets in bank of light-protective glass or bank polymeric, or in a bottle polymeric. Each can or a bottle, 2, or 5 blister strip packagings together with the application instruction are placed in a pack from a cardboard.