Valprok Hrono of the tab. of p/o of 300 mg No. 100

Pharmacological properties

Pharmacodynamics. anticonvulsant medicament of the prolonged action. inhibits gamk-transferase, brakes biotransformation gamk (inactivation), stabilizes and increases its contents in central nervous system. stimulates the central GABA-ergic processes (including brake a stress - limiting), reduces excitability and convulsive readiness of motor zones of a brain.

Shows tranquilizing properties, reduces sensation of fear, improves a mental condition and mood of patients. Highly effective at absentias epileptica and temporal pseudo-absentias epileptica, ineffective at psychomotor attacks.

Knows that in pharmacological researches Valproatum inhibited the different experimentally induced spasms (generalized and focal). Similarly and at people the antiepileptic effect of Valproatum can be noted in different types of epilepsy too.

In some researches in vitro observed promoting effect of Valproatum on replication of VICh-1. However this effect not especially expressed is also not reproduced in all experiments. Clinical consequences of this observation at the VICh-1-infitsirovannykh patients are unknown. These data need to be considered at assessment of measurements of viral load during sodium Valproatum use for the VICh-1-infitsirovannykh patients.

Pharmacokinetics

Absorption. Bioavailability of medicament — about 100%.

Drug Valprokom Hrono is present at blood in the form of valproic acid.

in a GIT. Its absorption is constant and long. Therefore there are no peaks of concentration of medicament in blood plasma, and therapeutic concentration of valproic acid are better maintained over time.

Distribution. The volume of distribution of valproic acid is mainly limited to blood and extracellular liquid which undergoes fast exchange.

Linking with blood proteins happens generally to albumine and is dose-dependent and saturated. At the general concentration of valproic acid in blood plasma of 40-100 mg/l a part of its free fraction mainly makes 6–15%.

valproic acid Level in SMZh similar to concentration of its untied substance in blood plasma (about 10%).

during dialysis, but the volume of the removed fraction considerably decreases as a result of its linking with albumine (about 10%).

at its concentration in blood plasma of 40-100 mg/l (278–694 µmol/l). At regular administration of medicament by Valprok Hrono the equilibrium concentration is established for the 3-4th day of therapy, in certain cases — through longer period. In case of keeping of the general level of valproic acid in blood plasma of 150 mg/l (1040 µmol/l) the decrease in a daily dose is necessary. More than 96% of medicament are exposed to intensive metabolism in a liver, 90 — 95% contact proteins of blood plasma, mainly albumine. Drug gets through GEB, a placental barrier, at use of the medicament Valprokom Hrono by the women nursing, valproic acid is excreted in breast milk (1–10% of the general concentration in blood plasma).

Metabolism. Metabolism of the medicament Valprokom Hrono mainly happens in a liver. The main metabolic ways are conjugation with glucuronic acid and β-oxidation. Unlike the majority of other antiepileptic drugs, Valproatum of sodium does not accelerate own degradation or degradation of other substances, such as estrogen-progestageny. This feature indicates that it does not induce the enzymes entering the metabolic system of P450 cytochrome.

Removal. Throughout a long time average T _½ valproic acid at adults makes 10.6 h (but can vary from 5 to 20 h) of blood plasma that 2 times a day are a basis for the scheme of dosing.

At the full-term babies of T _½ is made by 20-30 h. However it quickly approaches the values characteristic of adults, moderately how the baby grows.

mainly with kidneys.

not changed, but the most part is defined in urine in the form of metabolites.

Pharmacokinetics of separate groups of patients

At patients with a renal failure. Level of linking with albumine is reduced. Thus, it is necessary to consider the increase in free fraction of valproic acid in blood plasma which is a consequence of it and to respectively reduce a dose.

At patients of advanced age. Changes of pharmacokinetic parameters are revealed, but they were insignificant.

Thus, for selection of a dose decisive.

Indication

Main indication to medicament use valproky hrono, it is desirable as monotherapy, primary generalized epilepsy is: small epileptic seizures / absansny epilepsy, massive bilateral myoclonic spasms, big attacks of epilepsy with a myoclonia or without it, photosensitive forms of epilepsy.

Also as monotherapy or in a combination with other antiepileptic medicaments it is effective in the following diseases:

• secondary generalized epilepsy, especially Vest's syndrome (spasms at children of early age) and Lennox's syndrome — Gasto;
• partial epilepsy with simple or complex symptomatology (psychosensorial forms, psychomotor forms);
• epilepsy with secondary generalization;
• mixed epilepsy forms (generalized and partial).

Treatment of the episodes of a mania associated with bipolar affective disorders in the presence of contraindications to use or intolerance of lithium.

Prevention of a recurrence of dysthymic episodes at adult patients with bipolar disorders which at treatment of episodes of a mania have a therapeutic response to therapy by Valproatum.

Use

Valprok hrono is the form of medicament with the slowed-down release of active ingredient allowing to lower maximum and providing more uniform concentration of active ingredient in blood plasma within a day. to take the medicament inside, it is desirable at meal time. the daily dose is recommended to be accepted in 1 or 2 receptions. single use is possible in case of well controlled epilepsy. to swallow of a tablet whole, without crushing and without chewing, washing down with a half of a glass of water, milk or other soft drink. because of process of long release of medicament and like excipients as a part of medicament the inert matrix is not soaked up in a GIT, it is removed in the course of an excrement after release of active ingredient.

Epilepsy

Usual dose. The daily dose is defined according to age and body weight of the patient. However it must be kept in mind that the range of individual sensitivity to Valproatum rather wide. The optimum dose is established according to the received clinical answer. At unsatisfactory control of spasms or at suspicion on a possibility of development of side reactions can be necessary, except clinical observation, definition of concentration of medicine in blood plasma.

Therapeutic the range of concentration of 40-100 mg/l (300–700 µmol/l) is considered.

first line. Thanks to a dosage form of Hrono (the prolonged action) the daily dose of medicament can be applied at one time. The medicament should be taken at the beginning of meal.

Most often should apply such daily doses:

• 25 mg/kg — for children;
• 20-25 mg/kg — for teenagers;
• 20 mg/kg — for adults;
• 15-20 mg/kg — for patients of advanced age.

, therapy by the medicament Valprokom Hrono should be begun gradually.

Initial daily dose of Valproatum makes 10–15 mg/kg, then the dose should be increased gradually before achievement of an optimum dose.

If the patient does not take any other antiepileptic drugs, the dose should be increased gradually at an interval of 2–3 days to reach an optimum dose approximately in a week.

For the patients taking other anticonvulsant drugs, the Valprokom Hrono medicament treatment it is necessary to begin gradually to reach clinically effective dose approximately during 2 weeks then, depending on efficiency of treatment, to reduce doses of the medicaments taken at the same time.

if at use of medicament in the form of monotherapy such doses are reached: Elderly patients have 15 mg/kg/days, adults and teenagers have 20 mg/kg/days and children and babies have 25 mg/kg/days.

If clinical performance is satisfactory, the reached dose needs to be supported at this level. Elderly patients, 30 mg/kg have daily doses of 25 mg/kg at adults and teenagers and children and babies have 25 mg/kg, especially at use of Valproatum as monotherapy, seldom are necessary.

If these doses still do not allow to reach control of spasms, it is possible to continue to raise doses.

If the daily dose exceeds 50 mg/kg, it is recommended to divide it into 3 receptions, at the same time additional clinical inspections and control of indicators of biochemical analysis of blood are necessary (see. Special INSTRUCTIONS). In case of need uses of a combination of the medicament Valprokom Hrono with other antiepileptic means them should be entered into the scheme of treatment gradually.

Use of the medicament Valprokom Hrono in a combination with other antiepileptic means. It is necessary to begin sodium Valproatum use in the same way, as well as at monotherapy of the first line. The average daily dose is usually identical to the dose recommended for monotherapy. However in certain cases this dose can be increased by 5–10 mg/kg. Also it is necessary to consider influence of the medicament Valprokom Hrono on other antiepileptic means.

Replacement of other antiepileptic means by the medicament Valprokom Hrono. If it is going to replace gradually and completely the previous medicine with the medicament Valprokom Hrono, then it needs to be applied according to recommendations for monotherapy of the first line. A dose of certain previous medicines, especially barbiturates, at once gradually to reduce during 2–8 weeks before full cancellation.

mania Episodes at patients with bipolar disorder. The recommended initial dose — 20 mg/kg/days. This dose needs to be raised as soon as possible, the minimum therapeutic dose allowing to gain desirable clinical effect will not be reached yet.

As a rule, the desirable clinical effect is reached at concentration of Valproatum in blood plasma of 45-125 mkg/ml.

Dose can be adjusted depending on the individual clinical answer. The maximum dose should not exceed 3000 mg/days

Recommended maintenance dose of treatment in bipolar disorders — 1000–2000 mg/days

Children and teenagers: the efficiency and safety of medicament 500 Hrono for treatment of the episodes of a mania associated with bipolar disorders were not investigated by Valprok.

Prevention of a recurrence of episodes of a mania by which bipolar disorders are followed. The dose for prevention of a recurrence answers the smallest effective dose allowing to control as necessary symptoms of an acute mania at this patient. It is not necessary to exceed the maximum daily dose of 3000 mg.

female Children, female teenagers, women of reproductive age and pregnant women. Therapy by medicament needs to be begun and carried out under observation of the expert with experience of treatment of epilepsy. It is only necessary to appoint treatment this medicament when other types of therapy are inefficient or are not transferred by patients (see. Special INSTRUCTIONS and Use during pregnancy and feeding by a breast); the advantage and risk of use of this medicament need to be revised carefully at regular assessment of treatment. As a rule, the medicament Valprokom Hrono is appointed as monotherapy in the lowest dose at which the effect of treatment is observed and if it is possible, in the form of a dosage form with the prolonged release for avoidance of high peak concentrations in blood plasma. The daily dose needs to be divided at least into two receptions.

Valprok 300 Hrono:. Patients aged up to 18 years have assessment of efficiency and safety of medicament for treatment of maniacal episodes which are associated with bipolar disorders, was not carried out.

Valprok 500 Hrono. Drug is appointed to children with the body weight of 17 kg. This dosage form is not recommended to be applied at children under 6 years (there is a risk of hit in airways when swallowing).

to Children under 3 years recommends use of Valproatum as monotherapy, but prior to treatment it is necessary to estimate carefully therapeutic advantage of Valproatum concerning risk of damage of a liver or development of pancreatitis (see. Special INSTRUCTIONS).

needs to avoid simultaneous use of salicylates for treatment of children under 3 years because of risk of development of hepatotoxicity.

Contraindication

Hypersensitivity to Valproatum, divalproatum, a valpromid or other components of medicine in the anamnesis. acute hepatitis. chronic hepatitis. the cases of heavy hepatitis in the individual or family anamnesis of the patient which are especially caused by medicines. hepatic porphyria. a combination with meflokhiny and St. John's wort medicaments (see interactions). Valproatum is contraindicated to patients with the known mitochondrial disorders, caused by mutations in a nuclear gene which codes mitochondrial enzyme a polymerase scale (polg), for example with a syndrome of an alpers — a guttenlokher, to children up to 2 years at which presence of disorder connected with polg and also to patients with disturbance of an ornitinovy cycle is suspected of the anamnesis (see special instructions).

Side reactions are classified by

depending on development frequency: very often (≥1/100, 1/10); often (≥1/100, 1/10); infrequently (≥1/1000, 1/100); seldom (≥1/10,000, 1/1000); very seldom (≥1/10,000); frequency is unknown (it is impossible to estimate on the existing data).

Congenital, family and genetic disorders (see Use during pregnancy and feeding by a breast)

from digestive system: very often — nausea; often — vomiting, a disease of gums (generally a hyperplasia of gums), stomatitis, pain in epigastriums, diarrhea and other dispeptic disturbances develop in an initiation of treatment more often and, as a rule, pass independently within several days without medicament withdrawal. Frequency of developing of these disorders can be reduced considerably if to raise a dose of the medicament Valprokom Hrono very slowly, to take a pill, coated, the slowed-down release (Hrono) and to take the medicament at the beginning of meal. In these cases the symptomatic therapy can be appointed. Infrequently — cases of development of pancreatitis at which early medicament withdrawal is required.

can sometimes be

Consequence lethal (see. Special INSTRUCTIONS).

At all patients who complain of an acute pain in a stomach against the background of intake of Valproatum of sodium/valproic acid needs to perform immediately medical examination (analysis of enzymes of a pancreas, other appropriate laboratory researches).

Gepatobiliarny disorders: often — an abnormal liver function (tranzitorny increase in level of hepatic transaminases and level of bilirubin in blood plasma) (see. Special INSTRUCTIONS).

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It was reported about cases of emergence of severe damage of a liver, including a liver failure, sometimes with lethal consequences. Increase in level of liver enzymes, especially at the beginning of therapy, usually being tranzitorny.

from the respiratory system, bodies of a thorax and mediastinum: infrequently — a pleural exudate.

Mental disorders: very often — confusion of consciousness, aggression *, irritability, disturbance of attention *, hallucinations, excitability *; seldom — abnormal behavior *, psychomotor hyperactivity *, difficulties in uchebe*.

* These effects are observed by

mainly at children.

from central nervous system: very often — a tremor; often — drowsiness, a headache, a nystagmus, extrapyramidal disorders (sometimes irreversible), a stupor *, spasms *, a memory impairment, dizziness (in a case in/in an injection the dizziness arises in a few minutes after an injection and, as a rule, spontaneously passes still in a few minutes); infrequently — paresthesia, an ataxy, a melkoamplitudny postural tremor (first of all upper extremities, it can be temporary, the dose decline can be necessary), the isolated reversible parkinsonism, the isolated stuporny states, the lethargy sometimes leading to a tranzitorny coma (encephalopathy) isolated or in combination with paradoxical strengthening of the spasms which are coming to an end after cancellation or a dose decline of drug. Such cases arise at therapy by several medicines more often (in particular with phenobarbital or topiramaty) or after sharp increase in a dose of Valproatum. Seldom — very exceptional cases of disturbance of cognitive function with gradual emergence and the progressing development which can progress to full dementia are described and are reversible, disappearing after the termination of treatment for the period lasting from several weeks up to several months; very seldom — confusion of consciousness.

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It was reported about several cases of hyperactivity and irritability in an initiation of treatment, mainly at children.

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It was reported about sedation cases (especially at reception with other anticonvulsant drugs). Also there were messages about cases of a reversible syndrome of Parkinson which noted seldom.

from organs of hearing and balance: often — deafness (sometimes irreversible); frequency is unknown — a noise/ring in ears.

from the system of a hemopoiesis: often — anemia, thrombocytopenia (as a rule, asymptomatic at which at an opportunity the medicament dose decline taking into account the level of thrombocytes and extent of control of a disease is shown that usually promotes disappearance of thrombocytopenia); infrequently — a pancytopenia, a leukopenia; seldom — a macrocytosis, macrocytic anemia, an aplasia of red marrow or a true erythrocyte aplasia; agranulocytosis.

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It was reported about cases of decrease in level of fibrinogen or increase in duration of a bleeding time (especially at use of high doses of drug), as a rule, without clinical consequences. Valproatum inhibits the second phase of aggregation of thrombocytes.

Aplasia of red marrow or true erythrocyte aplasia.

information on the disturbances from sedimentation of blood corresponding to an angiohemophilia of the I type Exists.

needs to carry out by

blood test (the general complete blood count test with calculation of quantity of thrombocytes, definition of a bleeding time and carrying out tests for blood sedimentation, including determination of level of a factor of VIII) before therapy and also if at the patient the surgical intervention or in case of developing of a hematoma or spontaneous bleeding is planned.

from vessels: often — bleeding; infrequently — a vasculitis.

from an urinogenital system: infrequently — a renal failure, damage of kidneys; seldom — enuresis, urine incontinence, tubulointerstitsialny nephrite, a reversible syndrome of Fankoni, but the action mechanism is still not found out.

from skin and hypodermic cellulose: often — reactions of hypersensitivity, a tranzitorny and/or dose-dependent alopecia, damage of nails and a nail bed; infrequently — a Quincke's disease, rash, problems with hair (for example pathological texture of hair, discoloration of hair, pathological growth of hair); seldom — a toxic epidermal necrolysis, Stephens's syndrome — Johnson, a multiformny erythema, a hypersensitivity syndrome to medicament or DRESS syndrome (a syndrome of medicamentous rash with an eosinophilia and sisitemny symptomatology).

from a skeletal and muscular system: infrequently — decrease in bone mineral density, osteosinging, osteoporosis, fractures at the patients who are on long-term therapy using Valproatum; seldom — a system lupus erythematosus, a rhabdomyolysis.

Metabolic and alimentary disturbances: often — increase in appetite and increase in body weight (at 5–10% of patients), in particular at teenagers and young women. As increase in body weight can lead to deterioration in clinical symptoms of a syndrome of polycystic ovaries (see. Special INSTRUCTIONS), it is necessary to control body weight; hyponatremia. Seldom — the isolated and moderate giperammoniyemiya without changes from indicators of function of a liver, especially at therapy by several medicines, and it should not lead to the treatment termination. Also giperammoniyemiya cases with neurologic symptoms are described. In such cases the additional research is necessary (see also SPECIAL INSTRUCTIONS).

Endocrine disturbances: infrequently — a syndrome of inadequate secretion of antidiuretic hormone, a giperandrogeniye (hirsutism, a virilism, an acne, an androgenic alopecia and/or increase in levels of androgenic hormones); seldom — a hypothyroidism (see Use during pregnancy and feeding by a breast).

Reproductive disturbances: often — a dysmenorrhea, disturbances of a menstrual cycle; infrequently — an amenorrhea; seldom — risk of emergence of a polycystic syndrome of ovaries, infertility at men; very seldom — a gynecomastia.

Benign, malignant and not diagnosed new growths (including cysts and polyps): seldom — a miyelodisplastichesky syndrome.

Disorder, connected with pregnancy and a puerperal period, and perinatal disorders. Disturbances of intellectual development after pre-natal influence of Valproatum (see Use during pregnancy and feeding by a breast and SPECIAL INSTRUCTIONS).

General disorders. It was reported about hypothermia cases. It was very seldom reported about cases of developing of not heavy peripheral hypostases.

Results of researches: seldom — decrease in maintenance of blood-coagulation factors, aberrations from coagulation indicators (such as increase in a prothrombin time, increase in the activated partial tromboplastinovy time, increase in thrombin time, increase in an indicator of the international normalized relation). Against the background of use of the medicament Valprokom Hrono the number of thrombocytes can decrease by 10 000-30 000/mm ³ . In most cases such decrease is dose-dependent and tranzitorny. In this regard it is recommended to define quantity of thrombocytes to and in 3 and 6 months after an initiation of treatment and also before surgical intervention, especially if the dose exceeds 30 mg/kg/days. Seldom — deficiency of biotin / enzymatic activity of biotinidase.

Teratogenic risk (see Use during pregnancy and feeding by a breast).

Special instructions

Beginning of use of antiepileptic medicament can sometimes be followed by resuming of epileptic attacks or emergence of heavier attacks or development in the patient of new types of attacks, irrespective of spontaneous fluctuations which are observed at some epileptic states. first of all, it can be noted at changes in the scheme of combination therapy by antiepileptic medicaments and can be connected with pharmacokinetic interaction, toxicity or overdose.

sodium Valproatum which is one of active ingredients of the medicament Valprokom Hrono in a human body turns into valproic acid therefore it is not necessary to use at the same time other medicaments which are exposed to the same transformation in order to avoid valproic acid overdose (for example divalproatum, valpromid).

Children females/teenagers of the female/woman of reproductive age / pregnant women. Because of the high teratogenic potential and risk of disturbance of development in babies which were put at pre-natal influence of Valproatum the medicament Valprokom Hrono should not be used at female children, female teenagers, women of reproductive age and pregnant women, except for cases when alternative methods of treatment are inefficient or are not transferred by patients. The advantage and risk of use of this medicament have to be revised carefully at regular assessment of treatment, at puberty and in an immediate order when the woman of reproductive age taking the medicament Valprokom Hrono plans pregnancy or already became pregnant. Women of reproductive age have to use effective remedies of contraception during treatment by this medicine and have to be informed on the risk connected with use of the medicament Valprokom Hrono during pregnancy (see Use during pregnancy and feeding by a breast).

In particular, the doctor who appoints medicament has to be convinced that the patient understands:

• an essence and importance of the risks connected with influence of medicament during pregnancy, in particular teratogenic risks and risks of disturbance of development;
• need of use of effective remedies of contraception;
• need of regular assessment of treatment;
• need of the immediate address to the doctor in case of planning or veroyany approach of pregnancy.

Whenever possible, it is necessary to take all measures concerning replacement of medicament at the women planning pregnancy, the corresponding alternative method of treatment before fertilization (see Use during pregnancy and feeding by a breast).

only after revaluation by the doctor who has experience of treatment of epilepsy, advantage and risk of such therapy for the patient.

Severe damage of a liver

Condition of emergence. There are single messages about heavy or sometimes and lethal damages of a liver. Experience shows that the greatest risk, especially in case of a concomitant use of other antiepileptic drugs, is noted at babies and children under 3 years with heavy epilepsy, in particular, it concerns children with a brain damage, mental retardation and/or genetically caused metabolic or degenerative diseases.

At children aged from 3 years the risk considerably decreases which gradually decreases with age.

within the first 6 months of treatment, usually for 2–12 weeks, and is the most frequent — in complex antiepileptic therapy.

Is recommended to inform the patient (if the child — that his parents) that at emergence of the described clinical symptoms it is necessary to see a doctor immediately. Except clinical inspection it is necessary to carry out functional hepatic trials urgently.

Signs to which it is necessary to pay attention. The early diagnosis of hepatotoxicity is based on a clinical picture. In particular, it is necessary to consider symptoms which can precede jaundice, and other symptoms testifying to hepatotoxicity:

• general symptoms and signs (usually appear suddenly): for example drowsiness, an asthenia, confusion of consciousness, the excited state, anorexia, an abdominal pain, vomiting, bleeding and hypostasis;
• recurrence of epileptic attacks: despite observance of doctor's instructions.

Identification. The research of function of a liver should be conducted prior to therapy, and then to carry out regularly within the first 6 months of treatment. During therapy it is regularly necessary to control functional trials of a liver (level of aminotransferases, bilirubin, crude protein), blood clotting (prothrombin time, fibrinogen, a factor of VIII), quantity of thrombocytes, activity of a lipase and alpha amylase in urine. At identification of abnormally low level of the prothrombin which is especially followed by considerable decrease in level of fibrinogen and factors of blood clotting, increase in level of bilirubin and transaminases the treatment by Valproatum has to be suspended. Risk of development of side effects from a liver is increased at combination therapy with other antiepileptic means.

as a precautionary measure and also at simultaneous use it is necessary to stop therapy by salicylates as they have an identical metabolic way. It is necessary to make repeatedly laboratory analyses depending on the revealed changes of indicators.

Pancreatitis. Pancreatitis cases which sometimes came to an end letalno were seldom noted. These cases did not depend on age of the patient and duration of treatment. Pancreatitis most often arises at children of younger age or at patients with heavy epilepsy, injury of a brain, or at the patients accepting complex antiepileptic therapy. If pancreatitis is followed by a liver failure, the risk of emergence of lethal cases considerably increases.

At patients with acute abdominal pain or such gastrointestinal symptoms as nausea, vomiting and/or anorexia, it is necessary to carry out differential diagnostics with pancreatitis and at increase in levels of transaminases immediately to cancel medicament and to resort to alternative therapeutic actions.

Patient and/or his family have to ask immediately for medical care at emergence of symptoms of pancreatitis (such as abdominal pain, nausea and vomiting). In the presence of the symptoms testifying to pancreatitis the medical examination, including determination of level of a lipase and/or amylase in blood plasma has to be performed. At suspicion of pancreatitis the use of the medicament Valprokom Hrono should be stopped immediately.

as a precautionary measure, considering risk of hepatotoxicity, it is not necessary to apply derivatives of salicylic acid along with this drug.

At children under 3 years needs to use the medicament Valprokom Hrono only as monotherapy. At patients of this age group the therapy should be begun only after assessment of clinical advantages and risks of damage of a liver or development of pancreatitis. Together with it it is not necessary to apply salicylates at children aged up to 16 years (see reference information about acetylsalicylic acid / salicylates at Ray's syndrome).

At children with the obscure symptoms from a liver and a digestive tract (anorexia, vomiting, cytolysis cases), a lethargy or a coma in the anamnesis, with a delay of intellectual development, in case of a lethal outcome at the baby or the child in the family anamnesis prior to the Valprokom Hrono medicament treatment it is necessary to conduct a metabolism research, especially the test for an ammoniyemiya on an empty stomach and after meal.

needs to control free concentration of valproic acid in blood of patients with a renal failure and at its increase respectively to reduce a medicament dose.

Valproatum of sodium increases risk of a giperammoniyemiya at patients with disturbance of a cycle of ureapoiesis. Such patients should avoid sodium Valproatum use. At such patients the giperammoniyemiya cases which were followed by a stupor or a coma are described. Though in the course of treatment disturbances of functions of the immune system arise Valproatums exclusively seldom, patients need to compare possible advantage of use of the medicament Valprokom Hrono to potential risk when prescribing medicament with a system lupus erythematosus.

before therapy or surgery, in case of spontaneous hematomas or bleedings recommends to carry out blood test (to define a blood count, including quantity of thrombocytes, a bleeding time and coagulative tests).

Before an initiation of treatment of patients should warn about a possibility of increase in body weight that can be risk factor of development of a syndrome of a polycystosis of ovaries at women. Therefore the body weight of patients should be monitored carefully, it is necessary to take the appropriate measures, mainly dietary character