Mezakar

General characteristics. Structure:

Active ingredient: carbamazepine; 5 ml of suspension contain carbamazepine 100 mg.

Auxiliary veshchestva:ksantanovy gum; gipromelloza; potassium sorbate; citric acid, monohydrate; propylene glycol; sorbite the solution which is not crystallizing (Е 420); sucrose; yellow decline of FCF (Е 110); flavoring Orange additive; the flavoring Vanillin additive, water purified.

Pharmacological properties:

Pharmacodynamics. Carbamazepine has antiepileptic, neurotropic and psychotropic effect. As antiepileptic means drug is active concerning partial convulsive attacks (simple and difficult), without or with secondary generalization; generalized toniko-clonic spasms, and also combination of these types of convulsive attacks.
The mechanism of effect of carbamazepine, active ingredient of drug, is installed only partially. Carbamazepine stabilizes membranes of hyperactive nervous cells, suppresses repeated categories of neurons, reduces synoptic distribution of exciting impulses. Perhaps, anticonvulsant effect of carbamazepine is connected with the prevention of repeated categories by blockade of natrium channels.

Pharmacokinetics. Carbamazepine is soaked up from tablets almost completely, but rather slowly. After a single dose of a usual tablet the maximum concentration in plasma (Cmax) is reached in 12 hours, and in a liquid form - in 2 hours. Between peroral dosage forms there is no clinically significant difference in number of active agent which is absorbed. After a single dose of a dose of 400 mg of carbamazepine (tablet) average maximum concentration of not changed carbamazepine in a blood plasma makes about 4,5 mkg/ml.
It was shown that bioavailability of carbamazepine in various peroral means is in limits of 85-100%.
Meal significantly does not influence the speed and extent of absorption irrespective of a dosage form of carbamazepine.
Steady plasma concentration of carbamazepine are reached within about 1-2 weeks depending on an individual autoinduktion of carbamazepine and heteroinduction by other means inductors of enzymes, and also from the status before treatment, a dosage and duration of treatment.
Bioavailability of various drugs of carbamazepine can change; to avoid effect of decrease in bioavailability, risk of emergence of spasms or overshot side effects, can be reasonable not to replace drug with another.

Distribution. Carbamazepine contacts proteins of a blood plasma within 70-80%. Concentration of not changed substance reflects a share of substance in cerebrospinal fluid and saliva, untied with proteins of a blood plasma (20-30%). Concentration in breast milk, equivalent 25-60% of appropriate level of plasma were found.
Carbamazepine passes through a placental barrier. Assuming full absorption of carbamazepine, the expected volume of distribution fluctuates from 0,8 to 1,9 l/kg.

Biotransformation. Carbamazepine is metabolized in a liver where the epoxy way of biotransformation is the most important, forming the main metabolites – derivative 10,11 transdiols and a glucuronide.
It was defined that P450 3A4 cytochrome is the main isoform responsible for education carbamazepine-10, 11 epoxides from carbamazepine. Human microsomal epoxide-hydrolase it was defined as the enzyme responsible for education derivative 10,11 transdiols from carbamazepine-10,11-epoxide. 9-hydroxy-methyl-10-karbamoilakridan is a secondary metabolite of this way. After a single dose of a dose of carbamazepine about 30% are found in urine as end products of an epoxy way.
Other important ways of biotransformation of carbamazepine lead to various monohydroxylated compounds, and also a N-glucuronide of carbamazepine which is formed by UGT2B7.

Removal. Semi-removal of not changed carbamazepine averages about 36 hours after a single dose of a dose, after repeated introduction the elimination half-life on average makes only 16-24 hours (an autoinduktion of hepatic monooksigenazny system) depending on treatment duration. At the patients receiving simultaneous treatment by other fermentozavisimy drugs (for example, Phenytoinum, phenobarbital), the elimination half-life averages 9-10 hours.
The average elimination half-life of a 10,11-epoxy metabolite in a blood plasma makes about 6 h after reception of a dose of epoxide.
After a single dose of a dose of 400 mg of carbamazepine of 72% also 28% - with a stake are removed with urine. In urine about 2% of a dose appear in not changed look and about 1% - as pharmacological an active 10,11-epoxy metabolite.

Indicators of patients. Steady concentration of carbamazepine in a blood plasma which are considered as "the therapeutic range" considerably differ internally - individually; there were messages that at most of patients range made 4-12 mkg/ml that corresponds to 17-50 mmol/l. Concentration carbamazepine-10, 11 epoxides (pharmacological an active metabolite) makes about 30% of carbamazepine level.
Because of the strengthened carbamazepine removal higher doses of carbamazepine (in mg/kg), than the adult can be required by children for maintenance of therapeutic concentration.
At patients of advanced age no signs of the changed carbamazepine pharmacokinetics in comparison with patients of young age are revealed.
Patients have no data on carbamazepine pharmacokinetics with abnormal liver functions or kidneys.

Indications to use:

Epilepsy: generalized toniko-clonic and partial convulsive attacks.
Paroxysmal pain at neuralgia of a ternary nerve.
Prevention of maniac-depressive psychoses at patients in the absence of therapeutic effect at them of lithium drugs.

Route of administration and doses:

Drug can be accepted in time either after food, or in intervals between meals together with a small amount of liquid.
Мезакар®, suspension, is applied orally. Usually the dose is divided into 2-3 receptions.
As the maximum level of concentration of carbamazepine during administration of drug in the form of suspension is higher in comparison with a similar dose of drug in the tableted form, it is recommended to begin reception of suspension with low doses and gradually to increase them (in order to avoid side reactions from TsNS, such as dizziness and drowsiness).
When replacing of the tableted drug form by suspension it is necessary to apply the same dose, but it needs to be divided into smaller single doses and to respectively increase the number of receptions.
For faces of certain ethnic groups (Chinese, Thais) before an initiation of treatment it is desirable to carry out screening of HLA-B*1502 as existence of this allele is a predictive marker of possible risk of emergence of a syndrome of Stephens-Johnson of heavy degree connected with carbamazepine.

Epilepsy.
Children. Treatment is begun with use of a low daily dose which is slowly raised further to achievement of optimum effect for each patient. For selection of an optimum dose of drug there can be useful a determination of level of active agent in a blood plasma (see the sections "Pharmacokinetic Properties", "Features of Use", "Interaction with Other Medicines and Other Types of Interactions").
The usual dose makes 10-20 mg/kg of body weight a day which is divided into several single doses.
Children aged till 1 year: 100 – 200 mg of 1 times a day.
Children at the age of 1–5 years: 200 – 400 mg 1–2 times a day.
Children at the age of 5–10 years: 400 – 600 mg 2–3 times a day.
Children at the age of 10–15 years: 600 – 1000 mg 2–3 times a day.
It is necessary to appoint whenever possible antiepileptic means separately (in the form of monotherapy). At Mezakar's appointment, suspension, in addition to the current antiepileptic therapy the dose is gradually raised, without changing a dose of current applied antiepileptic drug(s) or, if necessary, adjusting it (see the section "Interaction with Other Medicines and Other Types of Interactions").
Adults. Treatment is begun with use of a low daily dose which is slowly raised further to achievement of optimum effect for each patient. For selection of an optimum dose of drug there can be useful a determination of level of active agent in a blood plasma (see the sections "Pharmacokinetic Properties", "Features of Use", "Interaction with Other Medicines and Other Types of Interactions").
For adults the initial dose makes 200-400 mg 1-2 times a day. Then the dose is slowly raised to achievement of optimum effect; usually it is reached at the dose of 800-1200 mg a day divided into 2 or more receptions. Increase in a dose of drug up to 1600-2000 mg/days can be required by some patients.
Patients of advanced age. Due to strengthening of interaction with other medicines patients of advanced age of a dose of carbamazepine need to select with care.

Epileptiform neuralgia.
The initial dose of the drug Mezakar®, suspension, makes 200-400 mg. It is slowly raised to disappearance of pain (usually to the dose of 600-800 mg divided into 3-4 receptions). In certain cases use of a dose of 1600 mg a day can be required. The recommended initial dose for patients of advanced age makes 200 mg a day, in 2 receptions. Then the dose is gradually reduced to the minimum supporting.
Prevention of maniac-depressive psychoses at patients at which there is no therapeutic response to treatment by lithium.
The initial dose makes 100-200 mg a day, distributed on several single doses. It is slowly raised to such which gives the chance to control disease symptoms, or before achievement of a daily dose of 1600 mg. Usually daily dose makes 400-600 mg, distributed on several receptions.

Features of use:

Usually carbamazepine is inefficient at small epileptic and myoclonic convulsive seizures. Besides, separate data indicate that at patients with atypical small epileptic convulsive seizures their aggravation is possible.

Caution
Carbamazepine appoint only under control and only after ratio assessment advantage/risk and at fixed monitoring of patients with cordial, hepatic or renal disturbances, side hematologic reactions to other drugs in the anamnesis or patients with the interrupted courses have therapies by drug carbamazepine.

Hematologic effects. Using drug connect development of an agranulocytosis and aplastic anemia, however because of extremely low frequency of cases of development of these states the risk connected using carbamazepine is estimated as insignificant. Temporary or permanent decrease in number of thrombocytes or leukocytes in blood in connection with carbamazepine reception is periodically or often noted. However for the majority of these cases their temporariness is confirmed, and they do not demonstrate development of aplastic anemia or an agranulocytosis. Prior to therapy and periodically during its carrying out it is necessary to do blood test, including determination of quantity of thrombocytes (and also, perhaps, quantities of reticulocytes and level of hemoglobin).
It is necessary to inform patients and their relatives information on the precursory symptoms of toxicity inherent to possible hematologic disturbances, and also on symptoms from integuments and a liver. The patient should be informed on need to see immediately a doctor in case of such undesirable reactions as fever, a pharyngalgia, rash, ulcers in oral cavities, causeless developing of bruises, hemorrhages in the form of petechias or a purpura.
If during treatment the low level of number of leukocytes or thrombocytes (or the tendency to decrease takes place) is noted, it is necessary to watch a condition of the patient and indicators of the developed clinical blood test attentively. At development of the expressed leukopenia progressing or with clinical manifestations like fever or a pharyngalgia, drug should be cancelled. If signs of considerable oppression of marrow are revealed, drug also should be cancelled.

Function of a liver. During therapy by drug it is necessary to carry out assessment of function of a liver at the initial level and periodic estimates of this function, especially at patients with liver diseases in the anamnesis and at patients of advanced age. At an aggravation of abnormal liver functions or at an active phase of a disease of a liver it is necessary to stop administration of drug immediately.
At some patients accepting carbamazepine, results of testing of function of a liver can go beyond norms, especially indicators gamma глутамилтрансферазы. It, perhaps, is result of induction of liver enzymes. Induction of enzymes can cause insignificant increase in an alkaline phosphatase also. Such strengthening of metabolizing ability of a liver is not the indication to carbamazepine cancellation.

Mental effects. Suicide thoughts and behavior at the patients treated by antiepileptic means according to several indications were noted. The metaanalysis randomized, placebo - a controlled research of antiepileptic medicines also showed slight increase of risk of suicide thoughts and behavior. The mechanism of such risk is unknown, the existing data do not exclude a possibility of the increased risk in connection with carbamazepine. Therefore it is necessary to control suicide thoughts and behavior of patients and to make the decision of rather corresponding treatment. Patients (and to people who look after patients) should recommend to see a doctor in case of signs of suicide thoughts or behavior.

Heavy dermatological reactions. Heavy dermatological reactions which include a toxic epidermal necrolysis (TEN or a Lyell's disease) the Stephens-Johnson's syndrome (SJS), at use of carbamazepine arise very seldom. Patients with heavy dermatological reactions can need hospitalization as these states can threaten life and have lethal character. The majority of cases of development of SSD/TEN are noted within the first several months of treatment by carbamazepine. At development of the signs and symptoms testimonial of serious dermatological reactions (for example, SSD, a syndrome of Layella / TEN), administration of drug it is necessary to stop and appoint alternative therapy immediately.
It was noted that at Chinese and Thais at treatment carbamazepine with HLA-B * closely connected 1502 risk of development of a syndrome of Stephens-Johnson. If it is possible, these persons before an initiation of treatment carbamazepine need to carry out screening of this allele. If the test showed a positive take, there is no need to begin treatment with carbamazepine, except for other therapeutic indications. Patients, results have testings for HLA-B * 1502 in which negative, risk of SSD low though reactions occasionally can arise.
Due to the lack of data it is authentically not known whether all persons a sort from the countries of Southeast Asia are exposed it to risk.
It was noted that the risk of development of a syndrome of Stephens-Johnson in representatives of the people of the Caucasus is closely connected with HLA-B allele * 1502.

Other dermatological reactions. Development of passing and easy dermatological reactions which do not threaten health, for example, of the isolated macular or makulopapulezny dieback is possible. Usually they pass in several days or weeks, both at reception of identical doses, and after a dose decline. At the same time, as it is sometimes very difficult to distinguish precursory symptoms of more serious dermatological reactions from moderate fleeting reactions, the patient has to be under observation immediately to stop drug use if with its continuation reaction worsens.

Hypersensitivity. Carbamazepine can provoke development of reactions of hypersensitivity, including multiple reactions of hypersensitivity, with localization in skin, a liver, the hemopoietic bodies and lymphatic system or other bodies, in total or separately, within system reaction.
Patients with reactions of hypersensitivity to carbamazepine have to be informed that about 25-30% of such patients can also have reactions of hypersensitivity on окскарбазепин.
At use of carbamazepine and Phenytoinum development of cross hypersensitivity is possible.
Generally, at emergence of the signs and symptoms indicating hypersensitivity, reception of carbamazepine should be stopped immediately.
Carbamazepine should be applied with care to patients with the mixed attacks which include absentias epileptica (typical or atypical). Under such circumstances drug can provoke attacks. In case of provoking of attacks use of drug should be stopped immediately.
Increase in frequency of attacks is possible upon transition from peroral forms of drug to suppositories. Carbamazepine contains parahydroxybenzoates which can cause allergic reactions (perhaps late) in a liquid form. It also contains sorbite and therefore it should not be appointed to patients with rare hereditary diseases of intolerance of fructose.

Sudden cancellation of carbamazepine can pretsipitirovat attacks
If treatment by carbamazepine was cancelled suddenly, then, if necessary, a transfer of the patient into other antiepileptic means should be made the corresponding drug (for example, diazepam in/in, rektalno or Phenytoinum in/in).

Carbamazepine and drugs of estrogen and/or progestogen
Because of induction of enzymes of a liver carbamazepine can become the reason of decrease in therapeutic effect of drugs of estrogen and/or progesterone. It can lead to unsuccessful contraception, a recurrence of symptoms or uterine bleeding, or bloody allocations.
Patients who accept carbamazepine and who need to accept hormonal contraceptives should use the drug containing not less than 50 mkg of estrogen or other alternative contraceptives.

Monitoring of level of drug in a blood plasma. In spite of the fact that correlation between a dosage and level of carbamazepine in a blood plasma, and also between carbamazepine level in a blood plasma and clinical performance and portability is doubtful, monitoring of level of drug in a blood plasma can be reasonable in the following cases: at sudden increase in frequency of attacks, check of a komplayns of the patient, at pregnancy, at treatment of children, at suspicion on absorption disturbance, at the suspected toxicity and at use more than one drug.

Function of kidneys. It is recommended to carry out assessment of function of kidneys and determination of level of an urea nitrogen at the beginning and periodically during a therapy course.

Anticholinergic effects. Carbamazepine shows moderated by anticholinergic activity. Thus, patients with the increased intraocular pressure have to be under observation during therapy.

Mental effects. It is necessary to remember probability of activation of latent psychosis at patients of advanced age – confusion of consciousness or excitement.

Ability to influence speed of response at control of motor transport or work with other mechanisms.
Ability of the patient react can be broken by the dizziness and drowsiness caused by carbamazepine, especially in an initiation of treatment or in connection with dose adjustment therefore patients have to show appropriate care during driving or work with mechanisms.

Use during pregnancy or feeding by a breast.
Use during pregnancy
Treatment by carbamazepine of the pregnant women sick with epilepsy, it is necessary to perform with extra care.
If it is possible, women of reproductive age should use drug in the monotherapy mode as the frequency of congenital anomalies of a fruit at women to whom treatment by a combination of antiepileptic means, above, than at receiving each of these means in the form of monotherapy was carried out.
If the woman who accepts Mezakar ® suspension, became pregnant or plans pregnancy or if the question of purpose of drug arises during pregnancy, it is necessary to compare the expected advantages of therapy and its possible complications, especially in the first three months of pregnancy. It is necessary to appoint a drug minimal effective dose. Regular control of level of active agent in a blood plasma is recommended.
During pregnancy it is not necessary to stop effective antiepileptic treatment as the exacerbation of a disease constitutes danger to mother and a fruit.
It is known that children who are born at mothers sick with epilepsy are more often than others are inclined to disturbances of pre-natal development, including malformations. Patients should provide information on a possibility of increase in risk of developing of malformations and an opportunity to undergo antenatal diagnosis.
Antiepileptic means increase deficit of folic acid. It can promote increase in frequency of inborn defects at the children who were born at the women accepting antiepileptic means. Therefore 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.
There are messages on several cases of spasms and/or respiratory depressions, vomitings, diarrheas and/or a loss of appetite for newborns whose mothers accepted drugs of carbamazepine and other antiepileptic means. These reactions can be withdrawal signs.
Use during feeding by a breast
Carbamazepine gets into breast milk, concentration in it are equal to 25-60% of level in a blood plasma. Therefore it is necessary to compare advantages and possible undesirable effects of breastfeeding in the conditions of therapy by Mezakar, suspension. Mothers accepting drug can nurse the children, but provided that for the child observation on development of possible side reactions will be established (for example, the expressed drowsiness, allergic skin reactions).

Children.
 Children can accept Mezakar® suspension since the birth.

Side effects:

Certain types of side reactions, for example, from the central nervous system (CNS) (dizziness, a headache, an ataxy, drowsiness, the general weakness, a diplopia), the alimentary system (nausea, vomiting) or allergic skin reactions arise very often or often, especially in an initiation of treatment Mezakar, suspension, at use of too high initial dose of drug or at treatment of patients of advanced age.
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 control the level of active agent in a blood plasma and to divide a daily dose into 3-4 receptions (instead of 2-3).
For assessment of frequency of emergence of various side reactions use such gradation: very often - ≥ 10%, are frequent - ≥ 1% to <10%, infrequently - from ≥ 0,1% to <1%, is rare - from ≥ 0,01% to <0,1%, is very rare - <0,01%

Interaction with other medicines:

P450 3A4 cytochrome (CYP 3A4) is the main enzyme providing formation of carbamazepine-10, 11 epoxides. Simultaneous use with carbamazepine of CYP 3A4 inhibitors can lead to increase in concentration of carbamazepine in plasma that, in turn, can cause emergence of side reactions. Combined use of the inductors CYP 3A4 can lead to acceleration of metabolism of carbamazepine and, thus, to possible decrease in concentration of carbamazepine in plasma and therefore - to possible reduction of expressiveness of therapeutic effect.
Similar to phase-out of inductors of CYP 3A4 enzyme can lower a metabolic rate of carbamazepine and lead to increase in its concentration in a blood plasma.
Drugs which can increase the level of carbamazepine and/or carbamazepine-10, 11 epoxides in plasma: isoniazid, verapamil, diltiazem, ритонавир, dextropropoxyphene, fluoxetine, флувоксамин; perhaps – Cimetidinum, омепразол, acetazoleamide, даназол, niacinamide (at adults – only in high doses); Trazodonum, вигабатрин, makrolidny antibiotics (for example, erythromycin, кларитромицин); azoles (for example, итраконазол, кетоконазол, флуконазол, вориконазол); лоратадин, olanzapine, кветиапин, grapefruit juice, inhibitors of proteases for treatment of HIV infection (for example, ритонавир). It was reported about increase in concentration of an active metabolite carbamazepine-10, 11 epoxides under the influence of a kvetiapin, Primidonum and valproic acid.
As increase in level of carbamazepine and/or carbamazepine-10, 11 epoxides in a blood plasma can lead to emergence of side reactions (for example, dizziness; drowsiness; ataxy; diplopia); it is necessary to adjust a dose of carbamazepine and/or to regularly investigate carbamazepine levels in a blood plasma.
The drugs reducing carbamazepine level in plasma: phenobarbital; Phenytoinum and фосфенитоин; Primidonum or theophylline; Aminophyllinum; rifampicin; Cisplatinum or doxorubicine and though data are partially contradictory, perhaps, also clonazepam or valproic acid, окскарбазепин. Meflokvin can counteract anticonvulsant effect of carbamazepine. Therefore there can be a need for carbamazepine dose adjustment.
It was reported that изотретиноин changes bioavailability and/or clearance of carbamazepine and carbamazepine-10, 11 epoxides, in this case monitoring of concentration of carbamazepine in a blood plasma is required.

Concentration of carbamazepine in a blood plasma can decrease at simultaneous use with a St. John's Wort by made a hole (Hipericum perforatum).
Influence of carbamazepine on concentration in a blood plasma of drugs which use as the accompanying therapy. Carbamazepine can reduce concentration or reduce and even completely to level effects of some drugs. Correction of doses of the following drugs can be required: left thyroxine, to klobaza, clonazepam, Ethosuximidum, Primidonum, valproic acid, to alprazola, corticosteroids (for example, Prednisolonum, dexamethasone); cyclosporine, digoxin, doxycycline, dihydropyridine derivatives (for example, фелодипин and израдипин); индинавир, саквинавир, ритонавир, a haloperidol, Imipraminum, methadone, paracetamol, трамадол, the drugs containing estrogen and/or progesterone (selection of alternative methods of contraception, see the section "Features of Use"), гестринон, тиболон, торемифин, theophylline, peroral anticoagulants (warfarin and ацетокумарол), ламотриджин, тиагабин, топирамат, бупропион is necessary, for tsitalopra, Trazodonum, tricyclic antidepressants (for example, Imipraminum, amitriptyline, нортриптилин, кломипрамин), clozapine, окскарбазепин, olanzapine, кветиапин, итраконазол, иматиниб and рисперидон.
There are messages that at carbamazepine reception Phenytoinum level in a blood plasma can both increase, and to decrease, and Mephenytoinum level – to increase (in some cases).

Combinations which should be considered. There are messages on strengthening of the hepatotoxic caused by an isoniazid when it was accepted along with carbamazepine.
The combined use of carbamazepine and lithium can lead to strengthening of a neurotoxicity in spite of the fact that lithium level in a blood plasma remains within therapeutic range. The combined use of carbamazepine or Metoclopramidum or big tranquilizers (a haloperidol, thioridazine) can lead to increase in frequency of undesirable neurologic reactions.
As carbamazepine has structural similarity to tricyclic antidepressants, it is not appointed in a combination with monoamine oxidase inhibitors (MAO), before purpose of drugs of carbamazepine MAO inhibitors should be cancelled at least in 2 weeks or if the clinical situation, even allows earlier.
Simultaneous use of carbamazepine with some diuretic means (a hydrochlorothiazide, furosemide) can lead to the hyponatremia which is followed by clinical manifestations.
Carbamazepine can counteract effects of not depolarizing muscle relaxants (for example, a pankuroniya). In case of use of such combination of medicines there can be a need of increase in a dose of the specified muscle relaxants; it is necessary to watch attentively patients as cancellation of muscle relaxants is possible quicker, than it was expected.
Carbamazepine, as well as other psychotropic drugs, can reduce portability of alcohol. In this regard the patient is recommended to refuse alcohol intake.

Contraindications:

Hypersensitivity to carbamazepine and similar medicines in the chemical relation (for example, to tricyclic antidepressants) or to any other component of drug.
Blockade, existence in the anamnesis of episodes of suppression of a marrowy hemopoiesis or hepatic porphyria (for example, the acute alternating porphyria, the mixed porphyria, a late porphyria of skin). A combination with monoamine oxidase inhibitors (MAO) (see the section "Interaction with Other Medicines and Other Types of Interactions") simultaneous use with lithium drugs.

Overdose:

Symptoms. The symptoms and complaints arising at overdose usually reflect defeat central nervous, cardiovascular and respiratory systems.
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.
Respiratory system: respiratory depression, fluid lungs.
Cardiovascular system: tachycardia, arterial hypotension, sometimes – arterial hypertension, disturbances of conductivity with expansion of the QRS complex; the cardiac standstill which is followed by a loss of consciousness.
Digestive tract: vomiting, a delay of passing of food from a stomach, decrease in motility of a large intestine.
Urinary system: ischuria, oliguria or anury, liquid delay; intoxication of cultivation (hyponatremia) caused by the effect of carbamazepine similar to effect of antidiuretic hormone.
Changes from laboratory indicators: a hyponatremia, the metabolic acidosis is possible, the hyperglycemia, increase in muscular fraction of a kreatininfosfokinaza is possible.

Treatment. There is no specific antidote.
At first treatment depends on a clinical condition of the patient; hospitalization is shown. Carry out definition of concentration of carbamazepine in a blood plasma for confirmation of poisoning with this means and assessment of extent of overdose.
Carry out a gastric lavage, apply absorbent carbon. Carry out the symptomatic supporting treatment in intensive care unit, control functions of heart, adjust electrolytic frustration.
Special recommendations
At development of arterial hypotension intravenous administration of a dopamine or Dobutaminum is shown.
At development of disturbances of a heart rhythm treatment is selected individually.
At development of spasms - administration of benzodiazepines (for example, diazepam) or other anticonvulsants, for example, phenobarbital (with care in connection with the increased risk of development of respiratory depression) or paraldehyde.
At development of a hyponatremia (cultivation intoxication) - restriction of administration of liquid, slow, careful infusion of 0,9% of solution of sodium of chloride. These measures can be useful to prevention of wet brain.
Carrying out hemosorption on coal sorbents is recommended. It was reported about inefficiency of an artificial diuresis, hemodialysis and peritoneal dialysis.
It is necessary to provide a possibility of repeated strengthening of symptoms of overdose for the 2nd and 3rd day after its beginning that is caused by the slowed-down drug absorption.

Storage conditions:

To store at a temperature not above 25 °C in the place, unavailable to children. After the first opening of a bottle to store drug no more than 4 weeks.

Issue conditions:

According to the recipe

Packaging:

On 100 ml of suspension in a bottle, on one bottle with a measured glass in a cardboard box.