Carbamazepine

General characteristics. Structure:

Active ingredient: 200 mg of carbamazepine in 1 tablet.

Excipients: cellulose microcrystallic, polysorbate-80 (twin-80), potato starch, silicon dioxide colloid, povidone, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. Antiepileptic means (derivative dibenzazepine), renders also antidepressive, antipsychotic and antidiuretic action. Possesses also analgeziruyushchy action at patients with neuralgia.

The mechanism of action is connected with blockade of potentsialzavisimy Na + - channels that leads to stabilization of a membrane of neurons, inhibition of emergence of serial categories of neurons and decrease in synoptic carrying out impulses. Prevents repeated formation of Na + - dependent action potentials in the depolarized neurons. Reduces release of exciting neuromediator amino acid of a glutamate, raises a reduced convulsive threshold of the central nervous system and, thus, reduces risk of development of an epileptic attack. Increases conductivity for K+, modulates potentsialzavisimy Sa2+-channels that can also cause anticonvulsant effect of drug.

Adjusts epileptic changes of the personality and, eventually, increases skill to communicate of patients, promotes their social rehabilitation. It can be appointed as the main therapeutic medicine and in combination with other anticonvulsants.

It is effective at the focal (partial) epileptic attacks (simple and complex) which are followed or not followed by secondary generalization, at generalized toniko-clonic epileptic attacks, and also at a combination of the specified types of attacks (it is usually inefficient at small attacks - petitmal, absentias epileptica and myoclonic attacks).

At patients with epilepsy (in particular at children and teenagers) positive influence on symptoms of uneasiness and a depression, and also decrease in irritability and aggression is noted. Influence on cognitive function and psychomotor indicators depends on a dose and is very variable.

The beginning of anticonvulsant effect varies from several hours to several days (sometimes up to 1 month owing to a metabolism autoinduktion).

At an essential and secondary epileptiform neuralgia in most cases prevents emergence of painful attacks. It is effective for simplification of a neurogenic pain at tabes, posttraumatic paresthesias and post-herpetic neuralgia. Easing of pains at an epileptiform neuralgia is noted in 8-72 h.

At a syndrome of alcoholic abstinence raises a threshold of convulsive readiness (which at this state is usually lowered) and reduces expressiveness of clinical manifestations of a syndrome (a hyperexcitability, a tremor, gait disturbances).

At patients with not diabetes mellitus leads to bystry compensation of a water balance, reduces a diuresis and feeling of thirst.

Antipsychotic (anti-maniacal) action develops in 7-10 days, can be caused by oppression of metabolism of a dopamine and noradrenaline.

Pharmacokinetics. Absorption is slow, but full, meal significantly does not influence the speed and extent of absorption. After a single dose inside the maximum concentration in a blood plasma of Cmax is reached in 12 hours. After a single dose in 400 mg of carbamazepine average Cmax value of not changed active agent makes about 4,5 mkg/ml. Time of achievement of the maximum concentration in a blood plasma (TCmax) - 4-5 h at intake.

Equilibrium concentration of drug in plasma are reached in 1-2 weeks (speed of achievement depends on specific features of metabolism: autoinduktion of fermental systems of a liver, heteroinduction of another, at the same time applied means), 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 a bolynenstvo of patients of value from 4 to 12 mkg/ml (17-50 µmol/l) fluctuate.

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%. The seeming distribution volume - 0,8 - 1,9 l/kg. In cerebrospinal fluid and saliva of concentration are created in proportion to amount of active agent, untied with proteins (20 - 30%). Gets through a placental barrier.

Concentration in breast milk makes 25 - 60% of that 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. The main isoenzyme providing carbamazepine biotransformation in carbamazepine-10,11-epoxide is P450 cytochrome (CYP ZA4). As a result of these metabolic reactions a low-active metabolite 9-hydroxy-methyl-10 карбамоилакридан is formed as well. Can induce own metabolism. Concentration of carbamazepine-10,11-epoxide makes 30% of concentration of carbamazepine.

Elimination half-life (T1/2) after reception of a single peroral dose - 25 - 65 h (on average about 36 h), after repeated reception depending on duration of treatment of 12 - 24 h (owing to an autoinduktion of monooksigenazny system of a liver). At the patients receiving in addition other anticonvulsants - inductors of monooksigenazny system (Phenytoinum, phenobarbital), an elimination half-life 9 - 10 h are averaged.

After a single dose in 400 mg of carbamazepine of 72% of the accepted dose also 28% - with a stake are removed with urine. About 2% of the accepted dose are removed with urine in the form of not changed carbamazepine, about 1% - in the form of a 10,11-epoxy metabolite.

At children, owing to more bystry elimination of carbamazepine, use of higher doses of drug at the rate on 1 kg of body weight in comparison with adults can be required.

There are no data testimonial of the fact that the pharmacokinetics of carbamazepine changes at patients of advanced age (in comparison with adult persons of young age).

Data on carbamazepine pharmacokinetics with renal failures or a liver are not available for patients so far.

Indications to use:

Epilepsy (excepting absentias epileptica, myoclonic or sluggish attacks) - partial attacks with difficult and simple symptomatology, initially and for the second time generalized forms of attacks with toniko-clonic spasms, the mixed forms of attacks (monotherapy or in combination with other anticonvulsant drugs);

Idiopathic epileptiform neuralgia, epileptiform neuralgia at multiple sclerosis (typical and atypical), idiopathic neuralgia of a glossopharyngeal nerve.

Acute maniacal states (monotherapy and in combination with the drugs Li + and other antipsychotic medicines). Faznoprotekayushchy affective" frustration (including bipolar), prevention of aggravations, weakening of clinical manifestations at an aggravation.

Syndrome of alcoholic abstinence (uneasiness, spasms, hyper excitability, sleep disorders).

Diabetic neuropathy with a pain syndrome.

Polyuria and polydipsia of the neurohormonal nature at not diabetes mellitus of the central genesis.

Route of administration and doses:

Inside, regardless of meal, together with a small amount of liquid. At epilepsy when it is possible, it is necessary to appoint carbamazepine in the form of monotherapy. Treatment is begun with use of a small daily dose which in the subsequent is slowly raised to achievement of optimum effect.

Accession of carbamazepine to already carried out antiepileptic therapy should be carried out gradually, at the same time doses of the used medicines do not change or, if necessary, adjust.

For adults the initial dose makes 100-200 mg 1-2 times a day. Then a dose slowly increase to achievement of optimum medical effect (usually 400 mg 2-3 times a day, at most-1,6-2 g/days).
At an epileptiform neuralgia in the first day appoint 200-400 mg/days, gradually increase no more than on 200 mg/days up to the termination of pains (on average 400 - 800 mg/days), and then reduce to a minimal effective dose. At a pain syndrome of neurogenic genesis an initial dose - 100 mg 2 times a day in the first day, then a dose increase no more than on 200 mg/days, if necessary raising it on 100 mg each 12 h to easing of pains. A maintenance dose - 200-1200 mg/days in stages.

At treatment of patients of advanced age and patients with hypersensitivity an initial dose-100 of mg 2 times a day.

Syndrome of alcoholic abstinence: an average dose - 200 mg 3 times a day; in hard cases during the first several days it is possible to raise a dose to 400 mg 3 times a day. In an initiation of treatment at the heavy phenomena of abstinence it is recommended to appoint in combination with sedative and somnolent medicines (клометиазол, chlordiazepoxide).

Not diabetes mellitus: an average dose for adults - 200 mg 2-3 times a day.

The diabetic neuropathy which is followed by pains: an average dose - 200 mg 2-4 times a day.

At prevention of a recurrence of affective and schizoaffective psychoses - 600 mg/days in 3-4 receptions.

At acute maniacal states and affective (bipolar) frustration daily doses - 400-1600 mg. An average daily dose - 400-600 mg (in 2-3 receptions). At an acute maniacal state the dose is raised quickly, at a maintenance therapy of affective frustration. - gradually (for portability improvement).

Features of use:

Pregnancy and lactation. At pregnancy approach (at the solution of a question of purpose of carbamazepine during pregnancy) it is necessary to compare carefully expected advantages of therapy and its possible complications, especially in the first 3 months of pregnancy.

It is known that the children born at mothers having epilepsy are predisposed to disturbances of pre-natal development, including malformations. Carbamazepine, as well as all other antiepileptic means, is capable to increase risk of emergence of these disturbances. There are single messages on cases of inborn diseases and malformations, including not fusion of handles of vertebrae (spina bifida). Information on a possibility of increase in risk of malformations and an opportunity to undergo antenatal diagnosis has to be provided to patients.

Antiepileptic means increase the deficit of folic acid which is often observed during pregnancy that can promote increase in frequency of development of inborn defects in children (to and during pregnancy additional reception of folic acid is recommended). For the purpose of prevention of the raised bleeding at newborns to women in recent weeks of pregnancy, and also the newborn recommends to appoint K1 vitamin.

Carbamazepine gets into breast milk, it is necessary to compare advantages and possible undesirable effects of breastfeeding in the conditions of the continuing therapy. Mothers accepting Carbamazepine can nurse the children provided that for the child observation concerning development of possible side reactions will be established (for example, the expressed drowsiness, allergic skin reactions).

Several cases of epileptic attacks, vomitings, diarrheas and/or subnutrition, spasms and/or respiratory depression at newborns whose mothers accepted carbamazepine along with other anticonvulsants are described (perhaps, these reactions represent manifestations at newborns of a syndrome of "cancellation").

Drug is usually not effective at absentias epileptica and myoclonic attacks.

Drug has to be used only on condition of regular medical observation.

During administration of drug with various frequency the passing or permanent decrease in number of thrombocytes and leukocytes which in most cases is not a harbinger of the beginning of aplastic anemia or an agranulocytosis is noted. Before an initiation of treatment, and also periodically in the course of treatment it is necessary to carry out clinical blood tests, including calculation of number of thrombocytes and, perhaps, reticulocytes, and also to define concentration of iron in a blood plasma.

Before an initiation of treatment drug and periodically in the course of therapy recommends a research of the general analysis of urine and level of urea in blood, definition of concentration of electrolytes in blood serum (since development of a hyponatremia is possible). Before an initiation of treatment and in process the research of functions 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 strengthenings of already being available abnormal liver functions or at emergence of an active disease of a liver, drug should be cancelled.

Drug has weak cholinergic activity therefore at use of drug for patients with the increased intraocular pressure, constant control of this indicator is necessary.

Carbamazepine can reduce efficiency of the medicines containing estrogen and/or progesterone therefore women of reproductive age during treatment by drug need to apply alternative methods of protection from pregnancy.

Regular definition of concentration of carbamazepine in a blood plasma is necessary in the following situations: at sharp increase in frequency of attacks; for, to check whether the patient accepts drug properly; during pregnancy; at treatment of children or teenagers; at suspicion on drug absorption disturbance; at suspicion on development of toxic reactions if the patient accepts several medicines.

Separate messages on disturbances of male fertility and/or disturbances of a spermatogenesis are so far registered (the interrelation of these disturbances with reception of carbamazepine is not established yet).

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 in/in or rektalno or Phenytoinum entered in/in).

At the patients receiving antiepileptic drugs the increased risk of emergence of suicide behavior, including thoughts of a suicide is noted. In this regard it is necessary to control carefully a condition of the patient for the purpose of early detection of progressing of a depression, suicide behavior, other changes in mood or unusual behavior of the patient.

Influence on ability to manage vehicles and mechanisms. During treatment it is necessary to be careful when driving and other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

At assessment of frequency of occurrence of various side reactions the following gradation are used: very often - 10% and a thicket; often - 1-10%; sometimes - 0,1-1%; seldom - 0,01-0,1%; very seldom - 0,01% are more rare.

Dozozavisimy side reactions usually take place within several days as it is spontaneous, and after a temporary dose decline of drug. Development of side reactions from TsNS can be a consequence of relative overdose of drug or considerable fluctuations of concentration of active agent in a blood plasma. In such cases it is recommended to monitorirovat concentration of drug in plasma.

From a nervous system: very often - dizziness, an ataxy, drowsiness, the general weakness; often - a headache, accommodation paresis; sometimes - the abnormal involuntary movements (for example, a tremor, the "flitting" tremor - asterixis, dystonia, tics); nystagmus; seldom - orofatsialny dyskinesia, oculomotor disturbances, disturbances of the speech (for example, a dysarthtia), choreoathetoid frustration, peripheral neuropathy, paresthesias, a myasthenia, paresis; very seldom - a malignant antipsychotic syndrome.

Disturbances of mentality: seldom - hallucinations (visual or acoustical), a depression, a loss of appetite, anorexia, concern, aggressive - behavior, excitement, a disorientation; very seldom - activation of psychosis, suicide behavior (including thoughts of a suicide).

From skin and hypodermic fabrics: often - allergic reactions, allergic dermatitis, a small tortoiseshell; sometimes - exfoliative dermatitis, an erythrosis; seldom - a system lupus erythematosus, an itch; very seldom - a multiformny exudative erythema (including Stephens-Johnson's syndrome), a toxic epidermal necrolysis (Lyell's disease), photosensitivity, a multiformny and nodal erythema, disturbances of a xanthopathy, purple, an acne, perspiration, a hair loss.

Hypersensitivity reactions: seldom - multiorgan reactions of hypersensitivity of the slowed-down type with fever, skin rashes, a vasculitis (including a knotty erythema as manifestation of a skin vasculitis), the 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), can be also involved and other bodies (for example, lungs, kidneys, a pancreas, a myocardium, a large intestine). Very seldom - aseptic meningitis with a myoclonus and a peripheral eosinophilia, anaphylactoid reaction, a Quincke's disease, an allergic pneumonitis or eosinophilic pneumonia. At emergence of the allergic reactions stated above use of drug has to be stopped.

From blood and lymphatic system: very often - a leukopenia; often - thrombocytopenia, an eosinophilia; seldom - a leukocytosis, a lymphadenopathy, deficit of folic acid; very seldom - an agranulocytosis, aplastic anemia, a pancytopenia, anemia, a true erythrocyte aplasia, megaloblastny anemia, the acute "alternating" porphyria, a reticulocytosis, hemolitic anemia.

From digestive tract: very often - nausea, vomiting; often - dryness in a mouth; sometimes - diarrhea, a lock; seldom - an abdominal pain; very seldom - a glossitis, stomatitis, pancreatitis.

From cardiovascular system: seldom - disturbances of nutriserdechny conductivity, decrease or increase in arterial pressure; very seldom - bradycardia, arrhythmias, an atrioventricular block with unconscious states, 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 a liver and biliary tract: very often - increase in activity gamma глутамилтрансферазы (owing to induction of this enzyme in a liver) that usually has no clinical value; often - increase in activity of an alkaline phosphatase of blood; sometimes - increase in activity of "hepatic" transaminases; seldom - hepatitis cholestatic, the parenchymatous (hepatocellular) or mixed type, jaundice; very seldom - granulematozny hepatitis, a liver failure.

From endocrine system and a metabolism: often - hypostases, a liquid delay, increase in body weight, a hyponatremia and decrease in osmolarity of plasma owing to the effect similar to effect of antidiuretic hormone that in rare instances leads to water intoxication (a cultivation hyponatremia) which is followed by a lethargy, vomiting, a headache, a disorientation and neurologic disturbances; very seldom - a giperprolaktinemiya (can be followed by a galactorrhoea and a gynecomastia); decrease in concentration of L-thyroxine (free thyroxine, thyroxine, triiodothyronine) and increase in level of thyritropic hormone (usually is not followed by clinical manifestations); the disturbances of calcium-phosphorus exchange in a bone tissue (decrease in concentration of calcium and 25-hydroxy-cholecalciferol in plasma) leading to osteomalacy/osteoporosis; a hypercholesterolemia (including cholesterol of lipoproteids of high density) and a gipertriglitseridemiya.

From kidneys and urinary tract: very seldom - intersticial nephrite, a renal failure, a renal failure (for example, an albuminuria, a hamaturia, an oliguria, increase an urea/azotemia), the speeded-up urination, an ischuria, disorders of sexual function.

From skeletal and muscular and connecting fabric: seldom - muscular weakness; 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.

From respiratory system: very seldom - the hypersensitivity reactions which are characterized by fever, short wind, a pneumonitis or pneumonia.

Influence on results of laboratory researches: very seldom - a hypogammaglobulinemia.

Others: it was reported about exceptional cases of a hirsutism, however the causal interrelation of this complication with reception of carbamazepine remains not clear.

Interaction with other medicines:

CYP3A4 cytochrome is the main enzyme providing carbamazepine metabolism. Co-administration of carbamazepine with CYP3A4 inhibitors can lead to increase in its concentration in a blood plasma and cause side reactions. Combined use of the inductors CYP3A4 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 metabolism of carbamazepine and lead to increase in concentration of carbamazepine in plasma.

Increase concentration of carbamazepine in plasma: verapamil, diltiazem, фелодипин, dextropropoxyphene, вилоксазин, fluoxetine, флувоксамин, Cimetidinum, acetazoleamide, даназол, desipramine, niacinamide (at adults, only in high doses); macroleads (erythromycin, джозамицин, кларитромицин, тролеандомицин); azoles (итраконазол, кетоконазол, флуконазол), терфенадин, лоратадин, the isoniazid, the propoxyhair dryer, grapefruit juice, inhibitors of virus protease used at therapy of HIV infection (for example, ритонавир) - is required correction of the mode of dosing or monitoring of concentration of carbamazepine in plasma.

Phenobarbital, Phenytoinum, Primidonum, метсуксимид, фенсуксимид reduce concentration of carbamazepine, theophylline, rifampicin, cisplates, доксирубицин, it is possible: clonazepam, вальпромид, valproic acid, окскарбазепин and the vegetable drugs containing a St. John's Wort made a hole (Hypericum perforatum). Felbamat reduces concentration of carbamazepine in plasma and increases concentration of carbamazepine-10,11-epoxide, at the same time perhaps simultaneous decrease in concentration in serum of a felbamat.

There are messages on a possibility of replacement of carbamazepine by valproic acid and Primidonum from communication with proteins of plasma and increase in concentration pharmacological of an active metabolite (carbamazepine-10,11-epoxide).

Izotretinoin changes availability and/or clearance of carbamazepine and carbamazepine-10,11-epoxide (control of concentration of carbamazepine in plasma is necessary).

Carbamazepine can reduce concentration in plasma (to reduce or even completely to level effects) and to demand correction of doses of the following drugs: klobazama, clonazepam, an Ethosuximidum, Primidonum, valproic acid, an alprazolam, GKS (Prednisolonum, dexamethasone), cyclosporine, doxycycline, a haloperidol, methadone, peroral drugs containing estrogen and/or progesterone (selection of alternative methods of contraception), theophylline, peroral anticoagulants (warfarin, a fenprokumon, a dikumarol), a lamotridzhina, a topiramata, tricyclic antidepressants (Imipraminum, amitriptyline, a nortriptilin, a klomipramin), clozapine, a felbamat, a tiagabin, an okskarbazepin, inhibitors of the proteases applied at therapy of HIV infection (an indinavir, a ritonavir, a sakvinovir), blockers of calcium channels (group of digidropiridon, for example, фелодипин is necessary), an itrakonazola, left thyroxine, midazolam, an olazapin, a prazikvantel, a risperidon, a tramadol, a tsiprazidon.

There are messages that against the background of carbamazepine reception Phenytoinum level in a blood plasma can both increase, and to decrease, and Mephenytoinum level - to increase (in rare instances). Carbamazepine at combined use with paracetamol increases risk of its toxic influence on a liver and reduces a therapeutic effectiveness (paracetamol metabolism acceleration). Co-administration of carbamazepine with fenotiaziny, Pimozidum, thioxanthenes, molindony, a haloperidol, Maprotilinum, clozapine and tricyclic antidepressants leads to strengthening of the oppressing action on TsNS and to easing of anticonvulsant effect of carbamazepine. Monoamine oxidase inhibitors increase risk of development of hyperpyrexial crises, hypertensive crises, spasms, death (before purpose of carbamazepine monoamine oxidase inhibitors have to be cancelled, at least, for 2 weeks or if the clinical situation, even for bigger term allows). Simultaneous use of carbamazepine with diuretics (a hydrochlorothiazide, furosemide) can lead to the hyponatremia which is followed by clinical manifestations.

Carbamazepine weakens effects of not depolarizing muscle relaxants (pankuroniya). In case of use of such combination there can be a need of increase in a dose of muscle relaxants, at the same time it is necessary to carry out attentive observation of patients as perhaps more bystry termination of their action.

Carbamazepine reduces portability of alcohol, in this regard patients are recommended to refuse alcohol intake.

Accelerates metabolism of indirect anticoagulants, hormonal contraceptive drugs, folic acid, prazikvantet, can strengthen elimination of hormones of a thyroid gland. Accelerates metabolism of medicines for the general anesthesia (an enfluran, a halothane, Ftorotanum) with increase in risk of gepatoksichny effects; strengthens formation of nefrotoksichny metabolites of a metoksifluran.

Strengthens a hepatotoxic action of an isoniazid.

Myelotoxic means strengthen manifestations of a gematotoksichnost of carbamazepine. At joint reception of carbamazepine and a levetiratsetam strengthening of toxic effect of carbamazepine was in some cases noted.

Joint reception with grapefruit juice can increase carbamazepine level in plasma.

Contraindications:

Hypersensitivity to carbamazepine or similar medicines in the chemical relation (for example, to tricyclic antidepressants) or to other components of drug, disturbance marrowy - a hemopoiesis, the acute "alternating" porphyria, including in the anamnesis, an atrioventricular block, a concomitant use with monoamine oxidase inhibitors (structural similarity to tricyclic antidepressants).

With care. With care it is necessary to use drug at the following states and diseases: dekompensirovanny chronic heart failure, a cultivation hyponatremia (a syndrome of hypersecretion of antidiuretic hormone, a hypopituitarism, a hypothyroidism, insufficiency of bark of adrenal glands), advanced age, active alcoholism (oppression of the central nervous system, carbamazepine metabolism amplifies), oppression of a marrowy hemopoiesis; liver failure, chronic renal failure, prostate hyperplasia, increase in intraocular pressure.

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.

Carbamazepine has to be immediately cancelled at emergence of the allergic reactions or symptoms presumably testimonial of development of a syndrome of Stephens-Johnson or a Lyell's disease. Slight skin reactions (the isolated macular or makulopapulezny dieback) usually take place within several days or weeks even at continuation of treatment or after a drug dose decline (the patient has to be under fixed observation of the doctor at this time). It is necessary to take into account a possibility of activation latentno of the proceeding psychoses, and patients of advanced age have a possibility of development of a disorientation or excitement.

Messages on emergence at women, bleedings during the period between periods in cases when along with carbamazepine oral contraceptives were applied are known. 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 patient is informed on need to see immediately a doctor in case of such undesirable reactions as fever, pharyngalgias, rash, an ulceration of a mucous membrane of an oral cavity, causeless developing of "bruises", hemorrhages in the form of petechias or a purpura. The Neprogressiruyushchaya the symptomatic leukopenia does not demand drug withdrawal, however treatment should be stopped at emergence of the progressing leukopenia or the leukopenia which is followed by clinical symptoms of an infectious disease.

At women of reproductive age carbamazepine has to be applied whenever possible in the form of monotherapy using minimum effective dose - frequency inborn, anomalies of the newborns born by women to whom the combined antiepileptic treatment, above, than at those who received each of these antiepileptic means in the form of monotherapy was carried out.

Overdose:

The overdose is shown usually by symptoms from the central nervous system, cardiovascular and respiratory systems.

Symptoms. From the central nervous system: oppression of functions of the central nervous system, a disorientation, drowsiness, excitement, hallucinations, unconscious states, a coma, visual disturbances ("fog" before eyes), the muffled speech, a dysarthtia, a nystagmus, an ataxy, dyskinesia, a hyperreflexia (in the beginning), a hyporeflexia (later), spasms, psychomotor frustration, a myoclonus, a hypothermia, a mydriasis.

From cardiovascular system: tachycardia, a lowering of arterial pressure, sometimes increase in arterial pressure, disturbance of intra ventricular conductivity with expansion of the QRS complex, a cardiac standstill.

From respiratory system: respiratory depression, fluid lungs.

From digestive tract: nausea and vomiting, a delay of evacuation of food from a stomach, decrease in motility of a large intestine.

From an urinary system: ischuria, oliguria or anury; liquid delay; cultivation hyponatremia.

Laboratory indicators: hyponatremia, metabolic acidosis, hyperglycemia and glucosuria, increase in muscular fraction of a kreatininfosfokinaza.

Treatment. The specific antidote is absent. Treatment is based on a clinical condition of the patient. Hospitalization, definition of concentration of carbamazepine in a blood plasma (for confirmation of poisoning with this drug and assessment of extent of overdose), a gastric lavage, purpose of absorbent carbon are shown (late evacuation of gastric contents can lead to the delayed absorption and repeated emergence of symptoms of intoxication during recovery). The symptomatic supporting treatment in intensive care unit, monitoring of functions of heart, body temperature, function of kidneys and a bladder, correction of disturbances of water and electrolytic balance.

The artificial diuresis, hemodialysis and peritoneal dialysis are inefficient (dialysis is shown at a combination of a serious poisoning and renal failure). Small children can have a need for hemotransfusion.

At a lowering of arterial pressure: it is shown in / ввведение a dopamine or Dobutaminum; at disturbances of a heart rhythm treatment is selected individually; at spasms - administration of benzodiazepines (for example, diazepam) or other anticonvulsants (for example, phenobarbital) with care because of possible strengthening of respiratory depression; at development of a hyponatremia of cultivation (water intoxication) - restriction of administration of liquids and slow in / ввведение 0,9% of NaCl solution (can promote prevention of development of defeat "a brain).

Carrying out hemosorption on coal sorbents is recommended.

Storage conditions:

In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

On 10, 15 20 or 30 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. On 1, 2, 3, 4, 5 blister strip packagings together with the application instruction in a pack from a cardboard.