Enkorat Hrono 200

General characteristics. Structure:

Active ingredients: 133,5 mg of Valproatum of sodium, 58 mg of valproic acid (together: 200 mg of Valproatum of sodium) in 1 tablet.

Excipients: a gidroksipropilmetiltsellyuloz (gipromelloz (2208, K-100)), a gidroksipropilmetiltsellyuloz (a gipromelloz (K-15MPremium, 2208)), corn starch, silicon dioxide colloid anhydrous, the talc purified magnesium stearate, the main butylated methacrylate copolymer (eudragit (E-100) of a granule), titanium dioxide (E-171), orange yellow (E110), a macrogoal 6000.

Pharmacological properties:

Pharmacodynamics. Enkorat Hrono 200 is an anticonvulsant of the prolonged action.

Shows antiepileptic activity at all types of epilepsy.

The most probable main mechanism of action of Enkorat Hrono 200 is strengthening of an inhibiting effect gamma аминобутировой acids (GABK) by means of impact on synthesis and metabolism gamma аминобутировой acids (GABK).

Pharmacokinetics. The prolonged absorption provides linear correlation between a dose and Enkorat Hrono's concentration 200 in a blood plasma, allows to receive more uniform concentration of drug within a day.

Enkorat Hrono 200 gets into cerebrospinal fluid and into a spinal cord.

Absorption. Enkorat Hrono 200 is quickly and almost completely soaked up. The peak of concentration in a blood plasma of the patient is reached within 2-8 hours after oral administration of drug. Bioavailability is close to 100%.

Distribution. Communication with blood proteins - 80 - 95%. Therapeutic activity of drug is shown at concentration in plasma of 278 - 694 mmol/l (40 - 100 mg/l) depending on concentration definition time, and also from reception of the accompanying medicines.

The amount of untied drug fluctuates from 6% to 15% of the general level of content of drug in a blood plasma. At exceeding of an effective therapeutic dose strengthening of side effect of Enkorat hrono can be observed.

Pharmacological and therapeutic effects of medicines with controlled release not always certainly are connected with the level of content of drug in a blood plasma.

Advantage of medicines with controlled release is an opportunity to avoid fluctuations of concentration of drug in a blood plasma within a day. It provides uniform and constant antiepileptic action for 24 hours.

The volume of distribution of Enkorat Hrono 200 makes 0 - 2 l/kg of body weight.

Metabolism and removal. It is metabolized generally in a liver and removed in the form of a glucuronide.

It is removed generally with urine. The insignificant amount of nemetabolizirovanny drug is removed with urine and a stake. The elimination half-life of Enkorat Hrono 200 makes from 8 to 22 hours.

Enkorat Hrono 200 is not the inductor of isoenzymes of system of P450 cytochrome, does not influence degree as own biotransformation, and biotransformation of other substances, such as estrogen, progestogens and antagonists of vitamin K.

Indications to use:

- Generalized epileptic attacks (clonic, tonic, toniko-clonic, absentias epileptica, myoclonic, atonic);

- Lennox-Gasto's syndrome;

- Partial epileptic attacks (partial attacks with secondary generalization or without it);

- Treatment and prevention of bipolar affective disorders (at adults).

Route of administration and doses:

Enkorat Hrono 200 is medicine of the prolonged action for intake. The main advantage of Enkorat Hrono 200 is a possibility of decrease in fluctuations of concentration of drug in a blood plasma for days. Enkorat Hrono 200 accept one or two times a day, it is preferable during food. The tablet is not chewed, swallowed entirely. The daily dose varies depending on age and the body weight of the patient.

Adults. An initial dose - 600 mg a day, then raise a dose on 200 mg with an interval three days to achievement of control over spasms. In most cases the dose, sufficient for control over spasms, makes from 1000 mg to 2000 mg a day, i.e. 20 - 30 mg/kg of body weight. If adequate control over spasms is not reached - it is necessary to increase a dose to 2500 mg a day.

Children with body weight more than 20 kg. An initial dose - 400 mg a day (irrespective of body weight), then gradually raise a dose to achievement of control over spasms. In most cases the dose, sufficient for control over spasms, makes 20 - 30 mg/kg of body weight a day. If adequate control over spasms is not reached - it is necessary to increase a dose to 35 mg/kg of body weight a day.

Children with body weight less than 20 kg. The alternative dosage form as titration of a dose of drug is necessary is used.

Elderly. The daily dose for elderly is determined by titration before achievement of control over spasms.

Distribution volume at elderly increases therefore linkng of drug with proteins of plasma decreases, therefore the content of untied drug increases. It has to be considered at clinical interpretation of level of drug in plasma.

For treatment of maniac-depressive psychosis with a bipolar current appoint Enkorat Hrono 200 in a dose 20 mg/kg a day.

Upon transition from tablets of immediate release which provided necessary control over a disease on Enkorat Hrono 200 it is necessary to keep a daily dose of drug.

Replacement of other antiepileptic drugs on Enkorat Hrono 200 should be made gradually, reaching an optimum dose approximately within 2 weeks. At the same time depending on a condition of the patient the dose of the previous drug decreases.

For the patients who are not accepting other antiepileptic drugs, doses should be increased in 2-3 days to reach an optimum dose approximately within a week.

In need of a combination with other anticonvulsants against the background of Enkorat Hrono's use the 200th such drugs should be administered gradually.

Features of use:

Pregnancy and period of feeding by a breast. Pregnancy. The risk connected with epilepsy and antiepileptic drugs. It was shown that when using any antiepileptic drugs at the women sick with epilepsy, the general frequency of inborn defects at the children born by them is 2 - 3 times higher, than among the general population (about 3%).

Though the increased number of children with inborn defects was noted in case of use of the combined medicinal therapy, the corresponding role actually of a disease and the drugs accepted by mother still is not established. The most often found malformations - a crevice of a lip and malformations of cardiovascular system.

It was reported about several cases of autism and the related disturbances at the children who transferred exposure by sodium Valproatum in a pre-natal state. However,  sudden interruption of antiepileptic treatment should be avoided as it can cause resuming of attacks and lead to harmful effects both for mother, and for a fruit.

The risk of malformations connected with Valproatum. At animals: pilot studies on mice, rats and rabbits showed teratogenic action.

At people: the available data confirm increase in frequency of malformations (including, in particular, disturbance of development of a neurotubule, a craniofacial dismorfiya, malformations of extremities, malformations of cardiovascular system, a hypospadias and other numerous anomalies with participation of various systems of an organism) at reception of Valproatum in comparison with some other antiepileptic drugs. The available data confirm communication between pre-natal influence of Valproatum and risk of a delay in development, in particular, of lag in the speech at children whose mothers accepted Valproatum during pregnancy. Data of meta-analysis (including registers and group researches) showed that the frequency of inborn malformations at children whose mothers accepted Valproatum as monotherapy during pregnancy makes 10,73%. (95% of DI: 8.16-13,29). The available data confirm a dozozavisimost of this phenomenon.

The delay in development is often connected with malformations, nevertheless, difficult to establish relationship of cause and effect taking into account possible concurrent factors, such as low indicators of IQ of mother or father, genetic, social and ecological factors, and also insufficient control of attacks at mother during pregnancy. At the children treated to action of Valproatum in mother's womb cases of frustration of an autistic range are registered. The abnormal result of pregnancy can be connected both with monotherapy by Valproatum, and with polytherapy. The available data confirm smaller probability of an abnormal result of pregnancy in case of monotherapy by Valproatum.

Due to the above, the following recommendations have to be taken into account: during pregnancy and to women of childbearing age it is necessary to appoint this drug only in case of obvious need (for example when other methods of treatment are inefficient or impossible because of intolerance). This assessment has to be made prior to treatment drug or if the woman of childbearing age accepting Hrono's ENKORAT plans pregnancy. Women of childbearing age have to be informed on risks and advantages of treatment by this drug during pregnancy, and also have to use effective contraception during treatment by drug.

If the woman plans pregnancy, or if pregnancy occurred recently, therapy Enkorat Hrono 200 has to be reconsidered irrespective of indications to use.

At treatment of bipolar disorders therapy by drug should be cancelled.

At epilepsy therapy by drug it is not necessary to stop advantage/risk without revaluation of a ratio. If after careful assessment of risks and advantage, the conclusion is drawn on a possibility of continuation of therapy by drug during pregnancy, it is recommended to use  the minimum  effective daily dose of drug which should be divided into several receptions in day. Use of a form of release of the prolonged action is preferable.

If necessary, for the purpose of minimization of risk of disturbance of development of a neurotubule, during pregnancy planning women are recommended to appoint folic acid in a dose of 5 mg/days.

It is necessary to carry out specialized monitoring of prenatal development for the purpose of identification of possible disturbances of development of a neurotubule and other malformations.

Newborns. This drug can cause a hemorrhagic syndrome in newborns whose mothers accepted sodium Valproatum during pregnancy.

The hemorrhagic syndrome is connected with thrombocytopenia, a hypofibrinogenemia, and/or decrease  in other      blood-coagulation factors,  was reported  also  about afibrinogenemiya cases, it is possible with a fatal outcome.

In case of use of Valproatum the hemorrhagic syndrome, apparently, is not connected with deficit of vitamin K.

At mother before childbirth it is necessary to carry out the analysis of number of thrombocytes, fibrinogen level in plasma and definition of time of coagulation (the activated tsefalinovy time: ATsV). Normal results at mother do not give the chance to completely exclude anomalies of a hemostasis at the newborn therefore after the birth carry out definition of number of thrombocytes and fibrinogen in plasma, and also time of coagulation (ATsV). The birth trauma can strengthen risk of bleeding.

Cases of a hypoglycemia are registered at newborns whose mothers accepted Valproatum during the third trimester of pregnancy.

Cases of a hypothyroidism are registered at newborns whose mothers accepted Valproatum during pregnancy.

Withdrawal (in particular, concern, irritability, hypererethism, a syndrome of the increased neuroreflex irritability, a hyperkinesia, disturbances of a tone of muscles, a tremor, spasms and frustration of meal) can arise at newborns whose mothers accepted Valproatum during the third trimester of pregnancy.

Breastfeeding. Allocation of Valproatum of sodium in breast milk low. However, in connection with data on decrease in verbal abilities at the children who underwent exposure by sodium Valproatum in a pre-natal state (see above) it is necessary to advise patients that it is undesirable to nurse.

Use at abnormal liver functions. Enkorat Hrono 200 is contraindicated at abnormal liver functions.

Use at renal failures. At use Enkorat Hrono 200 at patients with a renal failure can arise need for a drug dose decline.

Liver diseases. Prior to treatment and within the first 6 months of therapy periodic control of function of a liver is necessary, especially patients have risk groups.

At identification of small increase in activity of liver enzymes, especially in an initiation of treatment, recommend to conduct fuller laboratory examination (including, in particular, definition of a prothrombin ratio) for the purpose of correction of the mode in case of need; further inspection should be repeated.

Among classical tests the tests reflecting synthesis of protein in a liver and especially - a prothrombin ratio are most important. At considerable decrease in level of a prothrombin, the expressed reduction of content of fibrinogen, factors of coagulability of blood, increase in level of bilirubin and transaminases, treatment by Enkorat Hrono 200 should be suspended. If the patient receives at the same time salicylates, then they should be cancelled also immediately as salicylates and Enkorat Hrono 200 have the general ways of metabolism.

There are rare messages on hard cases of diseases of a liver with a lethal outcome. The group of the increased risk is made by children of a younger age group. With age the frequency of such complications decreases. In most cases the abnormal liver function was observed within the first 6 months of treatment, usually between 2 and 12 weeks, and most often - at the combined antiepileptic therapy.

Early diagnosis is based preferential on clinical inspection. In particular, it is necessary to take into account two factors which can precede jaundice, especially at the patients making risk group:

- the nonspecific general symptoms which are usually appearing suddenly, such as adynamy, the anorexia, extreme fatigue, drowsiness which sometimes are followed by the repeating vomiting and abdominal pains;

- a recurrence of epileptic seizures against the background of antiepileptic therapy.

It is necessary to warn the patient and if it is the child, then his family, about need to immediately inform the doctor of emergence of the specified symptoms. In addition to clinical inspection in such cases it is necessary to carry out the analysis of function of a liver immediately.

Pancreatitis. Severe forms of pancreatitis, sometimes - with a lethal outcome were in rare instances noted. These cases observed irrespective of age of the patient and duration of treatment though the risk of development of pancreatitis decreased with increase in age of patients. Insufficiency of function of a liver at pancreatitis increases risk of a lethal outcome.

Before therapy, before surgeries, when developing spontaneous hematomas or bleedings control of a picture of peripheral blood (with number of thrombocytes), definition of a bleeding time and carrying out coagulative tests is recommended.

At an acute pain abdominal syndrome and such symptoms as nausea, vomiting and/or anorexia, immediate inspection of the patient is necessary, and at confirmation of the diagnosis: pancreatitis - drug should be cancelled.

Renal failure. At Enkorat Hrono's use 200 at patients with a renal failure it is recommended to consider the increased concentration of free fraction of valproic acid in a blood plasma and to lower a dose.

System lupus erythematosus and other diseases of immune system. In need of purpose of drug patients with a system lupus erythematosus and other diseases of immune system should estimate the expected medical effect and possible risk of therapy as at Enkorat Hrono's use 200 in exclusively exceptional cases disturbances from immune system were noted.

It is not recommended to appoint drug to patients with deficit of enzymes of a carbamide cycle. At such patients several cases of the giperammoniyemiya which is followed by a stupor and/or a coma were described.

At children with inexplicable symptoms from the alimentary system (anorexia, vomiting, cytolysis cases), a lethargy or a coma in the anamnesis, with a delay of intellectual development or the instruction in the family anamnesis on death of the newborn or child, prior to treatment by Enkorat Hrono 200 metabolism researches, especially ammoniyemiya have to be conducted at starvation and after meal.

Patients need to be warned about risk of increase in body weight in an initiation of treatment and to recommend observance of a diet for minimizing of such influence.

As Enkorat Hrono 200 is brought generally by kidneys, partially in the form of whale bodies, at patients with a diabetes mellitus it can be the cause in a false manner of positive test result on ketonic bodies in urine.

Patients with insufficiency a carnitine palmitoyltransferase of the II type have to be informed on high risk of development of a rabdomioliz at medicine reception.

Women of childbearing age. Women of childbearing age should appoint this drug only in case of obvious need (for example when other methods of treatment are inefficient or impossible because of intolerance). This assessment has to be made prior to treatment drug or if the woman of childbearing age accepting Enkorat Hrono 200 plans pregnancy. Women of childbearing age have to use effective contraception during treatment by drug.

Suicide thinking and behavior. It was reported about cases of development of suicide thinking and behavior in the patients accepting antiepileptic drugs according to some indications. Meta-analysis of randomized placebos - controlled tests of antiepileptic drugs also showed existence of the increased risk of development of suicide thinking and behavior.

Thus, it is necessary to trace carefully at patients signs of a suicide myshleniye and behavior and to appoint the corresponding treatment. Patients (and to categories of patients) need to recommend to see a doctor at once after emergence of signs of development of suicide thinking and behavior.

Side effects:

Assessment of undesirable effects is based on the following data on emergence frequency: very often (≥1/10), it is frequent (≥1/100 to <1/10), sometimes (≥1/1, 000 to <1/100), is rare (≥1/10, 000 to <1/1000), is very rare (<1/10, 000), in some cases (it cannot be estimated on the basis of the available data).

Disturbances from blood and lymphatic system. Often: anemia, thrombocytopenia (see. Special instructions). Sometimes: pancytopenia, leukopenia. Seldom: oppression of function of marrow (including true erythrocyte aplasia), agranulocytosis, macrocytic anemia, macrocytosis.

Separate sluchaisnizheniye of level of fibrinogen and increase in a vremenikrovotecheniye, usually not having clinical effects are described especially when using high doses of drug. Valproatum renders the inhibiting effect on the second phase of aggregation of thrombocytes.

Disturbances from a nervous system. Very often: tremor. Often: extrapyramidal frustration, a stupor, drowsiness, spasms, a memory impairment, a headache, a nystagmus, dizziness can arise in a few minutes after intravenous administration and, usually, passes within several minutes. Sometimes: coma, drowsiness, reversible parkinsonism, ataxy, paresthesia. Seldom: the reversible dementia connected with a reversible brain atrophy, cognitive frustration. The stupor and a lethargy sometimes lead to a passing coma / encephalopathy; these cases were isolated or connected with increase of attacks of convulsions against the background of Valproatum, their frequency decreased after the termination of treatment or after a dose decline. Such states arose most often at the combined treatment (especially, in a combination with phenobarbital or topiromaty) or after sharp increase in a dose of Valproatum.

Disturbances from an acoustic organ and labyrinth disturbances. Often: relative deafness.

Disturbances from respiratory system, bodies of a thorax and a mediastinum. Sometimes: pleural exudate.

Disturbances from digestive tract. Very much chasto:toshnota. Often: vomiting, gingivalny diseases (generally a hyperplasia of gums), the stomatitises, stomach aches, diarrhea which are arising in an initiation of treatment and usually, passing in several days without demanding drug withdrawal. Sometimes: pancreatitis, sometimes from the death (see. Special instructions).

Disturbances from kidneys and urinary tract. Sometimes: renal failure. Seldom: enuresis, tubulointerstitsialny nephrite, a reversible syndrome of Fankoni, but the mechanism of effect of drug at such state remains obscure.

Disturbances from skin and hypodermic fabrics. Often: hypersensitivity, temporary and/or dozozavisimy hair loss. Sometimes: Quincke's edema, rash, change of texture, hair color, change of growth rate of hair. Seldom: a toxic epidermal necrolysis, a syndrome Stephens-Johnson, a mnogoformny erythema, medicinal rash in combination with an eosinophilia and system symptoms.

Disturbances from skeletal and muscular and connecting fabric. Sometimes: decrease in mineral density of a bone tissue, osteosinging, osteoporosis and fractures at the patients who are on prolonged treatment by drug. The mechanism by means of which drug influences metabolism of a bone tissue is not revealed. Seldom: a system lupus erythematosus (see. Special instructions), рабдомиолиз.

Disturbances from a metabolism and food. Often: hyponatremia. Seldom: a giperammoniyemiya (see. Special instructions). The chances of the isolated and moderate giperammoniyemiya which are not followed by changes from indicators of function of a liver; drug withdrawal is not required. At the same time, cases of the giperammoniyemiya proceeding with neurologic symptoms (are known up to a coma) and demanding carrying out additional analyses (see. Special instructions).

The high-quality, malignant and not specified new growths (including cysts and polyps). Seldom: miyelodisplastichesky syndrome.

Disturbances from endocrine system. Sometimes: a syndrome of inappropriate secretion of ADG, a giperandrogeniye (a hirsutism, a virilism, an acne, baldness on men's type and/or increase in level of androgens). Seldom: a hypothyroidism (see Pregnancy and breastfeeding).

Disturbances from vessels. Chasto:krovotecheniye (see. Special instructions and Pregnancy and breastfeeding). Sometimes: vasculitis.

The general frustration and disturbances in an injection site. Sometimes: fall of temperature of a body, peripheral hypostasis in not severe form.

Influence on results of laboratory and tool researches. Often: increase in body weight. As increase in body weight is risk factor of development of a syndrome of polycystic ovaries, careful control of body weight of patients is necessary (see. Special instructions). Seldom: decrease in factors of coagulability of blood (at least, one), distortion of results of coagulative tests (such as lengthening of a prothrombin time, lengthening the activated partial tromboplastinovy time, lengthening of thrombin time, MHO lengthening), deficit of vitamin N, deficit of biotinidase.

Disturbances from a liver and biliary tract. Often: injury of a liver (see. Special instructions).

Disturbances from generative organs and a mammary gland. Often: dysmenorrhea. Sometimes: amenorrhea. Seldom: male infertility, polycystosis of ovaries.

Disturbances of mentality. Often: confusion of consciousness, hallucination, aggression, concern, disturbance of attention. Seldom: abnormal behavior, psychomotor hyperactivity, learnability disturbance.

These disturbances it is observed preferential in pediatric population.

Interaction with other medicines:

Contraindicated combined use of Enkorat Hrono 200 and meflokhina, and also Enkorata Hrono 200 and drugs of a St. John's Wort.

At combined use of Enkorat Hrono 200 and a meflokhina development of spasms in connection with strengthening of biotransformation of valproic acid and ability of a meflokhin to cause spasms is possible.

At simultaneous use with drugs of a St. John's Wort there is a risk of reduction of concentration of Enkorat Hrono 200 in a blood plasma.

Combinations which are not recommended. At combined use Enkorat Hrono 200 can slow down metabolism of a lamotridzhin in a liver and increase its concentration in a blood plasma, and also increase probability of emergence of heavy skin reactions up to development of a toxic epidermal necrolysis (in need of a combination therapy careful clinical and laboratory control is required).

At simultaneous use of Enkorat Hrono 200 with carbamazepine there is an increase in concentration of its active metabolite in a blood plasma to overdose signs. Besides, carbamazepine strengthens Enkorat Hrono's metabolism 200 in a liver that leads to reduction of concentration of Enkorat Hrono 200 in a blood plasma (clinical observation, definition of concentration of drugs in a blood plasma, correction of their doses, especially in an initiation of treatment is recommended).

Combinations at which use extra care is required. At Enkorat Hrono's use 200 in a combination with meropenemy, panipenemy, and also, apparently, with aztreonamy and imipenemy decrease in concentration of Enkorat Hrono 200 in a blood plasma with increase in risk of emergence of spasms is possible (clinical observation, definition of concentration of drugs in a blood plasma is recommended, dose adjustment of Enkorat Hrono 200 can be required during treatment by an antibiotic and after its cancellation).

At combined use of a felbamat and Enkorat Hrono 200 increase in concentration of the last in a blood plasma and risk of development of overdose is possible (clinical and laboratory control and, perhaps, dose adjustment of Enkorat Hrono 200 is recommended during treatment felbamaty and after its cancellation).

At combined use Enkorat Hrono 200 increases concentration of phenobarbital and Primidonum in a blood plasma that leads to emergence of symptoms of overdose, usually at children. Besides, decrease in concentration of Enkorat Hrono 200 in a blood plasma, connected with strengthening of her metabolism in a liver under the influence of phenobarbital or Primidonum is observed (clinical monitoring during the first 15 days of the combined treatment with immediate reduction of a dose of phenobarbital or Primidonum at emergence of the first signs of sedation is recommended, definition of concentration of both anticonvulsant drugs in a blood plasma).

At simultaneous use of Enkorat Hrono 200 with Phenytoinum there is a risk of decrease in concentration of Enkorat Hrono 200 in a blood plasma that is connected with strengthening of metabolism of Enkorat Hrono 200 in a liver under the influence of Phenytoinum (clinical monitoring with definition of concentration of both drugs in plasma and if necessary - correction of their doses is recommended).

At simultaneous use with topiramaty the risk of development of a giperammoniyemiya or encephalopathy increases that it is caused by strengthening of action of Enkorat Hrono 200 (the strengthened clinical and laboratory control within the first month of treatment and in case of symptoms of an ammoniyemiya is recommended).

Enkorat Hrono 200 exponentiates action of neuroleptics, MAO inhibitors, antidepressants, benzodiazepines (clinical monitoring and, if necessary, dose adjustment of the corresponding drug is recommended).

At simultaneous use of Enkorat Hrono 200 with Cimetidinum or erythromycin increase in concentration of Enkorat Hrono in a blood plasma because of reduction of its biotransformation in a liver is possible.

At simultaneous use Enkorat Hrono 200 can increase concentration of a zidovudine in a blood plasma that leads to increase in toxicity of a zidovudine.

Combinations which should be taken into account. At simultaneous use with nimodipiny for intake (and parenterally) there is strengthening of hypotensive effect of a nimodipin owing to reduction of his metabolism under the influence of Enkorat Hrono and increase in concentration in a blood plasma.

At simultaneous use of Enkorat Hrono 200 and acetylsalicylic acid strengthening of effects of Enkorat Hrono 200 owing to increase in its concentration in a blood plasma is observed.

At simultaneous use with Enkorat Hrono of 200 indirect anticoagulants, antagonists of vitamin K careful monitoring of a prothrombin ratio is required.

Enkorata Hrono 200 does not cause induction of enzymes therefore at simultaneous use does not influence efficiency of the combined hormonal contraceptives containing estrogen and progesterone.

Influence on ability to driving of motor transport and to control of mechanisms. During treatment patients need to be careful when driving motor transport and other activity demanding high concentration of attention and speed of psychomotor reactions.

Contraindications:

- liver diseases in an active phase;

- the expressed abnormal liver function at the patient or in the family anamnesis (first of all medicinal genesis);

- porphyria;

- hypersensitivity to Valproatum or to any of medicine components;

- a combination with meflokhiny and a St. John's Wort.

Overdose:

Symptoms: a coma with a hypomyotonia, a hyporeflexia, a miosis, respiratory depression, a metabolic acidosis; cases of the intracranial hypertensia connected with wet brain are described.

Treatment: in a hospital - a gastric lavage if after administration of drug there passed no more than 10-12 h; monitoring and correction of a functional condition of cardiovascular and respiratory systems, maintenance of an effective diuresis. In very hard cases carry out dialysis. As a rule, the forecast is favorable, however several cases of a lethal outcome were described.

Storage conditions:

In the place protected from moisture, at a temperature not over 25 ºС. To store in the place, unavailable to children. A period of validity - 3 years. Medicine cannot be used after the termination of a period of validity.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in planimetric bezjyacheykovy packaging. 3 planimetric bezjyacheykovy packagings together with a leaf insert place in a pack from a cardboard.