Carbamazepine

General characteristics. Structure:

Active agent: carbamazepine – 200 mg, excipients: aerosil, potato starch, magnesium stearate, povidone (polyvinylpirrolidone), twin, talc.

Pharmacological properties:

Pharmacodynamics. The antiepileptic means derivative of dibenzazepine rendering also normotimichesky, anti-maniacal and analgetic action. Activates the central brake GAMK-ergichesky system. Blocks potential - dependent natrium channels of membranes of nervous cells that leads to functional stabilization of neurons. Reduces activity of exciting neuromediator acids (a glutamate, aspartate), interacts with the central adenosine receptors (adenylatecyclase activation suppression). Raises a convulsive threshold, reduces risk of development of epileptic means, and in combination with other anticonvulsant drugs. Increases conductivity for K+, models potentsialzavisimy Sa + channels that can also cause anticonvulsant effect of drug. Adjusts epileptic changes of the personality that leads to increase in skill to communicate of patients and their social rehabilitation. At an essential epileptiform neuralgia in most cases prevents emergence of paroxysmal pains. At an alcoholic abstinence syndrome raises a reduced convulsive threshold and, thus, reduces risk of development of a convulsive attack, also reduces expressiveness of clinical manifestations of a syndrome (a hyperexcitability, a tremor, affective frustration). At not diabetes mellitus reduces a diuresis and feeling of thirst (due to antidiuretic action). Anti-mental (anti-maniacal) effect develops in 7-10 days, can be caused by oppression of metabolism of a dopamine and noradrenaline.

Pharmacokinetics. Absorption - slow, but rather full (meal does not influence the speed and extent of absorption). After a single dose the maximum concentration (Cmax) is reached in 12 h. 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 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 (further SMZh) and saliva create concentration 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 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 3A4). As a result of these metabolic reactions it is formed as well a little active metabolite 9-hydroxy-methyl-10-karbamoilakridan. Can induce own metabolism. Is the inductor of the fermental CYP3A4, CYP3A5, CYP3A7 system in a liver. Concentration of carbamazepine-10,11-epoxide makes 30% of concentration of carbamazepine. An 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 treatment duration – 12-24 h (owing to an autoinduktion of monooksigenazny system of a liver). At the patients receiving in addition other anticonvulsant drugs (inductors of monooksigenazny system - Phenytoinum, phenobarbital) T1/2 - on average 9-10 h. It is removed in the form of inactive metabolites with urine (70%) and with a stake (30%). 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. There are no data demonstrating 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 yet.

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, idiopathic glossopalatine neuralgia, an alcoholic abstinence syndrome, treatment of yaffektivny frustration, a polydipsia and a polyuria at not diabetes mellitus, diabetic polyneuropathy.
Acute maniacal states (monotherapy and in combination with the drugs Li + and other anti-mental HP). Faznoprotekayushchy affective frustration (including bipolar) prevention of aggravations, weakening of clinical manifestations at an aggravation.
Prevention of faznoprotekayushchy affective disturbances (maniac-depressive psychosis, schizoaffective disorders, etc.).
Use is also possible (indications are based on clinical experience, controlled researches were not conducted):
- at psychotic frustration (at affective and schizoaffective disorders, psychoses, panic frustration, schizophrenia, resistant to therapy, dysfunction of limbic system),
- at an agressive behavior of patients with organic lesions of a brain, a depression, a chorea;
- at alarm, a dysphoria, somatization, a sonitus, senile dementia, a syndrome of Klyuvera-Byyusi (bilateral destruction of an amygdaloid complex), obsessivno-compulsive frustration, cancellation of benzodiazepine, cocaine;
- at a pain syndrome of neurogenic genesis: at back to tabes, multiple sclerosis, acute idiopathic neuritis (a syndrome Giyena-bar), diabetic polyneuropathy, stump neuralgias, a syndrome of "tired legs" (Ekbom's syndrome), a gemifatsialny spasm, posttraumatic neuropathy and neuralgia, post-herpetic neuralgia;
- for prevention of migraine.

Route of administration and doses:

Nazachat 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 drugs do not change or, if necessary, korrigirut. 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, as much as possible - 1600-2000 mg/days). For children from 4 months to 4 years the average daily dose makes 10-20 mg/kg of body weight: from 4 months to 1 year – 100-200 mg a day, from 1 year to 5 years - 200-400 mg (in 1-2 receptions), from 6 to 10 years – 400-600 mg (in 2-3 receptions), for 11-15 years – 600-1000 mg (in 2-3 receptions). Maintenance doses: 10-20 mg/kg a day (in stages). At an epileptiform neuralgia in the first day appoint 200-400 mg/days, then gradually raise a dose no more than on 200 mg a day up to the termination of pains, on average, to 600-800 mg a day, 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 a day, if necessary raising it on 100 mg each 12 h to easing of pains. A maintenance dose - 200-1200 mg a day in stages. At treatment of patients of advanced age and patients with hypersensitivity an initial dose - 100 mg 2 times a day. The diabetic neuropathy which is followed by pains: an average dose – 200 mg 2-4 times a day. Alcoholic abstinence syndrome: 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 disintoxication therapy and sedative and somnolent drugs. Not diabetes mellitus: an average dose for adults - 200 mg 2-3 times a day. For prevention of affective disturbances: in the first week the daily dose makes 200-400 mg (2 tablets). In the subsequent the dose is increased by 200 mg a week, bringing it to 1 g. The daily dose is divided evenly into 3-4 receptions. Just as at use of other antiepileptic drugs, transition to treatment by carbamazepine has to be gradual, with reduction of a dose of the previous drug. It is necessary to stop treatment by carbamazepine also gradually. Duration of treatment is established by the doctor individually. At acute maniacal states and affective (bipolar) frustration daily doses - 400-1600 mg. An average daily dose - 400-600 mg (at 2-3 reception). At an acute maniacal state the dose is raised quickly, at a maintenance therapy affective frustration - gradually (for portability improvement).

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 необхолдимо it is sharp to interrupt 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). Several cases of vomiting, diarrhea and/or subnutrition, spasms and/or respiratory depressions at newborns whose mothers accepted carbamazepine along with other anticonvulsant drugs are described (perhaps, these reactions represent manifestations at newborns of a withdrawal). 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 emergence of an active disease of a liver of drug it is necessary to cancel 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 electroencephalogram (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 emergence of reactions of hypersensitivity or symptoms presumably testimonial of development of a syndrome of Stephens-Johnson or a Lyell's disease. Poorly expressed 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). Carbamazepine has weak anticholinergic activity, at appointment its constant control is necessary for patients with the increased intraocular pressure. 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. 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). Messages on emergence at women of bleedings during the period between periods in cases when oral contraceptives were at the same time applied are known. Carbamazepine can negatively affect reliability of oral contraceptive drugs therefore women of reproductive age during treatment should apply alternative methods of protection from pregnancy. Carbamazepine has to be applied only under medical observation. 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 oral cavity, causeless developing of bruises, hemorrhages in the form of petechias or a purpura. In most cases passing or permanent decrease in number of thrombocytes and/or leukocytes are not harbingers of the beginning of aplastic anemia or an agranulocytosis. Nevertheless, 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 determine iron level in blood serum. Not progressing 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 also measurement in need of intraocular pressure is recommended to conduct ophthalmologic examination, including an eyeground research a slit lamp. In case of purpose of drug patients with increase in intraocular pressure need constant control of this indicator.
During treatment it is necessary to abstain from occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions. It is recommended to refuse the ethanol use.
Though the interrelation between a carbamazepine dose, its concentration and clinical performance or portability is very insignificant, nevertheless, regular determination of level of carbamazepine 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:

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 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 the level of active agent in a blood plasma.
From the central 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 or the muffled speech), choreoathetoid frustration, peripheral neuritis, paresthesias, muscular weakness and symptoms of paresis.
From the mental sphere: seldom - hallucinations (visual or acoustical), a depression, a loss of appetite, concern, an agressive behavior, excitement, a disorientation; very seldom - activation of psychosis.
Allergic reactions: often - a small tortoiseshell; sometimes – exfoliative dermatitis, an erythrosis; seldom - a volchanochnopodobny syndrome, an itch; very seldom - Stephens-Johnson's syndrome, a toxic epidermal necrolysis, photosensitivity, a multiformny and knotty eritma. Seldom - multiorgan reactions of hypersensitivity of the slowed-down type with the fever, skin rashes, a vasculitis, lymphadenopathy, signs reminding a lymphoma, arthralgias, a leukopenia, an eosinophilia, a gepatospleno-megaliya and the changed indicators of function of a liver (the specified manifestations meet in various combinations). Also other bodies can be involved (for example, lungs, kidneys, a pancreas, a myocardium, a large intestine). Very seldom - aseptic meningitis with a myoclonus, the anaphylactic reaction, a Quincke's disease, reactions of hypersensitivity from lungs which are characterized by fever, short wind, a pneumonitis or pneumonia. At emergence of the hypersensitivity reactions stated above use of drug has to be stopped.
From bodies of a hemopoiesis: very often - a leukopenia; often - thrombocytopenia, an eosinophilia; seldom - a leukocytosis, a limfoadenopatiya; very seldom - an agranulocytosis, aplastic anemia, a true erythrocyte aplasia, megaloblastichesky anemia, the acute alternating porphyria, a reticulocytosis, hemolitic anemia.
From the alimentary system (further GIT): very often - nausea, vomiting; often - dryness in a mouth; sometimes - diarrhea or a lock, abdominal pains; very seldom - a glossitis, stomatitis, pancreatitis.
From a liver: very often - increase in activity gamma глутамилтрансферазы (owing to induction of this enzyme in a liver) that usually does not matter; often - increase in activity of an alkaline phosphatase; 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 cardiovascular system (further CCC): seldom - disturbances of endocardiac conductivity; decrease or increase in arterial pressure; very seldom - bradycardia, arrhythmias, an atrioventricular block with faints, a collapse, aggravation or development of 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: - hypostases, a liquid delay, increase in body weight, a hyponatremia (decrease in osmolarity of plasma owing to the effect similar to action of ADG that in rare instances leads to the hyponatremia of cultivation which is followed by a lethargy, vomiting, a headache, a disorientation and neurologic disturbances); very seldom - increase in level of prolactin (can be followed by a galactorrhoea and a gynecomastia); decrease in level of L-thyroxine (free T4, T4, T3) and increase in level of thyritropic hormone (TTG) (usually is not followed by clinical manifestations); disturbances of calcium-phosphorus exchange in a bone tissue (decrease in concentration of Ca2 + and 25-OH-cholecalciferol in a blood plasma): osteomalacy; a hypercholesterolemia (including cholesterol and lipoproteins of the high density (LPVP) and a gipertriglitseridemiya.
From urinogenital system: 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 / impotence.
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.
Others: disturbances of a xanthopathy, purple, acne, perspiration, alopecia.

Interaction with other medicines:

Carbamazepine increases activity of microsomal enzymes of a liver and can reduce effect of the separate drugs which are metabolized in a liver (peroral anticoagulants, etc.). P450 cytochrome (CYP 3A4) is the main enzyme providing carbamazepine metabolism. Co-administration of carbamazepine with CYP 3A4 inhibitors can lead to increase in its concentration in a blood plasma and cause side reactions. Combined use of the inductors CYP 3A4 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, 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. 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. Concentration of carbamazepine is reduced by phenobarbital, Phenytoinum, Primidonum, метсуксимид, фенсуксимид, theophylline, rifampicin, Cisplatinum, doxorubicine, it is possible: clonazepam, вальпромид, valproic acid, окскарбазепин and the vegetable drugs containing a St. John's Wort made a hole (Hypericum perforatum). There are messages on a possibility of replacement by valproic acid and carbamazepine Primidonum from communication with proteins of plasma and increase in concentration pharmacological of an active metabolite (carbamazepine-10,11-epoxide). Izotretinoin changes bioavailability and/or clearance of carbamazepine and carbamazepine-10,11-epoxide (monitoring 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 alprazolama, glucocorticosteroids (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, olanzapine, 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 the level of Mephenytoinum to increase (in rare instances). Carbamazepine at combined use with paracetamol increases risk of its toxic influence on a liver and the therapeutic effectiveness (paracetamol metabolism acceleration) reduces. 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. MAO inhibitors - increase risk of development of giperpireticheky crises, hypertensive crises, spasms, death (before purpose of carbamazepine MAO inhibitors have to be cancelled, at least, for 2 weeks or if the clinical situation, even for bigger term allows). Co-administration with diuretics (a hydrochlorothiazide, furosemide) can lead to the hyponatremia which is followed by clinical manifestations. 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. Reduces portability of ethanol. Accelerates metabolism of indirect anticoagulants, hormonal contraceptive drugs, folic acid; prazikvantet, can strengthen elimination of hormones of a thyroid gland. Accelerates metabolism of anesthetics (an enfluran, a halothane, Ftorotanum) with increase in risk of gepatotoksichny effects; strengthens formation of nefrotoksichny metabolites of a metoksifluran. Strengthens a hepatotoxic 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, acute премежающаяся a porphyria (including in the anamnesis), a concomitant use of monoamine oxidase inhibitors (further MAO), disturbances
 marrowy hemopoiesis (anemia, leukopenia), atrioventricular block. blockade.
With care - a cultivation hyponatremia (a syndrome of hypersecretion of antidiuretic hormone (further ADG), a hypopituitarism, a hypothyroidism, insufficiency of bark of adrenal glands), advanced age, alcohol intake (oppression of TsNS amplifies, carbamazepine metabolism), oppression of a marrowy hemopoiesis against the background of reception of medicines (in the anamnesis amplifies); prostate hyperplasia, increase in intraocular pressure, heavy heart failure, liver failure, chronic renal failure.
Use during the periods of pregnancy and a lactation. At women of reproductive age carbamazepine has to be applied, whenever possible, in the form of monotherapy (using minimum effective dose) - the frequency of congenital anomalies of the newborns born by women to whom the combined antiepileptic treatment, above, than at those who received each of these means in the form of monotherapy was carried out. 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. 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 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 inborn defects at 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. 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). At the increased drowsiness of the child stop breastfeeding. 
Use at pregnancy For women of reproductive age carbamazepine has to be applied, whenever possible, in the form of monotherapy (using minimum effective dose) - the frequency of congenital anomalies of the newborns born by women to whom the combined antiepileptic treatment, above, than at those who received each of these means in the form of monotherapy was carried out. 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. 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 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 inborn defects at 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. 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). At the increased drowsiness of the child stop breastfeeding.

Overdose:

The symptoms and complaints arising at overdose usually reflect disturbances from TsNS, CCC and respiratory system:
Central nervous system: oppression of the TsNS functions, disorientation, drowsiness, excitement, hallucinations, coma; sight misting, muffled speech, dysarthtia, nystagmus, ataxy, dyskinesia, hyperreflexia (in the beginning), hyporeflexia (later); spasms, psychomotor frustration, myoclonus, hypothermia, mydriasis;
Cardiovascular system: tachycardia, a lowering of arterial pressure, sometimes increase in arterial pressure, disturbance of conductivity with expansion of the QRS complex; faints, cardiac standstill; respiratory system: respiratory depression, fluid lungs.
Digestive tract: nausea and vomiting, a food passage delay from a stomach, decrease in motility of a large intestine;
Urinary system: ischuria, oliguria or anury; liquid delay; cultivation hyponatremia.
Laboratory and tool data: the leukocytosis or leukopenia hyponatremia, is possible a metabolic acidosis, the hyperglycemia and a glucosuria, increase in muscular fraction of a kreatinfosfokinaza is possible.

Storage conditions:

List B. In the dry, protected from light place at a temperature not above 25 °C. To store in places unavailable to children. 
Period of validity of 5 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets of 200 mg: 10, 20, 30, 40 or 50 pieces.