Index of drugs

Primary epileptic seizures: typical and unusual attacks of the unconscious (petit mal), myoclonic seizures, tonic-clonic seizures (grand mal), mixed forms of tonic-clonic seizures and seizures of the unconscious, atonic attacks. The drug can also be used in other types of epilepsy, not responding adequately to other antiepileptic drugs, such as: partial epileptic seizures: both simple (focal) and complex (psychomotor); secondarily generalized seizures, especially akinetic and atonic seizures. In the case of primary generalized seizures, the drug can often be used as monotherapy. In partial seizures, it is more often necessary to introduce combination therapy, as in seizures of secondary generalized and mixed forms of primarily generalized and partial seizures. Treatment of manic episodes in bipolar disorder, when lithium is contraindicated or poorly tolerated. Continuation of valproate treatment may be considered in patients who have responded clinically to acute mania valproate therapy.

1 tabl sustained release contains 300 mg or 500 mg sodium valproate.

Anticonvulsant. The mechanism of action probably consists in increasing the concentration of GABA in the synaptic cleft. It also affects excitatory neurotransmitters. It can also have a direct effect on sodium and potassium channels in neuronal membranes. It is well absorbed after oral administration, bioavailability is 90-100% (food may increase the rate of absorption of the drug, but does not change the bioavailability). After a single dose of the preparation, the maximum concentration in the blood is reached after 8.6 +/- 2 h. In 90-95% it is bound to plasma proteins. Protein binding is reduced at higher doses of the drug, in elderly patients, with renal or hepatic impairment, and in people with hypoalbuminemia. Metabolism of the drug occurs in the liver, mainly in the process of glucuronidation and to a lesser extent in the oxidation process; urinary excretion. T_0,5 is 12-16 h, while patients taking medications that induce liver enzymes T_0,5 is 4-9 hours.

Hypersensitivity sodium valproate or any of the excipients. Chronic or acute hepatitis. Severe hepatic failure, especially drug-related history or family history. Severe pancreatic insufficiency. Porphyria. Bleeding tendency.

Because of the risk of severe hepatic impairment that may result in death, the drug should be used with caution in infants and children under 3 years of age with severe epilepsy, especially when they have mental retardation, brain damage, metabolic or degenerative disease. of a genetic background or a history of liver disease. In this group of patients, valproic acid should be administered as monotherapy. Most cases of hepatotoxic effects are observed within the first 6 months of treatment, especially between 2 and 12 weeks. In children over the age of 3, the risk of liver damage decreases with age. In young children, in patients with severe epilepsy, brain damage or when several antiepileptic drugs are used, the risk of acute pancreatitis which may be fatal increases at the same time. Hepatic failure combined with pancreatitis increases the risk of death. The concomitant use of valproate and salicylates should be avoided in children under 3 years due to the risk of liver toxicity and haemorrhage. The use of valproate in patients with urea cycle disorders is not recommended. In patients with systemic lupus erythematosus, the preparation should only be used after careful consideration of the risks and benefits of treatment. Patients with a history of bone marrow fracture should be carefully monitored. In patients with renal insufficiency, an increase in non-plasma protein valproic acid should be considered and the dose reduced as necessary.An immediate discontinuation of treatment should be considered in case of unexplained general deterioration, clinical manifestations of liver and / or pancreatic injury, coagulation disorders, over 2- or 3-fold increase in ALT or AST, also in the absence of clinical symptoms (consideration should be given induction of hepatic enzymes by co-administered drugs), moderate (1-1.5-fold) increase in ALT or AST, accompanied by acute fever infection, significant deterioration of coagulation parameters or occurrence of dose-related adverse reactions. There has been a slight increase in the risk of suicidal ideation and behavior in patients taking antiepileptic drugs - patients should be carefully monitored for signs of suicidal ideation and behavior and, if necessary, considered for alternative treatment. Co-administration of sodium valproate with carbapenems is not recommended. The safety and efficacy of the preparation in the treatment of manic episodes in bipolar disorder have not been established in patients under 18 years of age.

Because of the potential for birth defects and developmental defects in infants who have been exposed to valproate in the womb, for the treatment of epilepsy and bipolar disorder in patients who may become pregnant, valproate-containing medicines should only be prescribed when other forms of treatments are not effective or are not well tolerated. Patients should use effective contraception, and treatment should be under the supervision of a doctor who has experience in the treatment of these diseases. For patients who become pregnant or plan to become pregnant while on valproate therapy, alternative treatment options should be considered. The need for testing and a new benefit-risk benefit analysis for women and girls who take valproate should be regularly reviewed. Patients should be informed of the risk of valproate during pregnancy (information on pregnancy in accordance with EMA recommendations of 21/11/2014). Valproate penetrates to a small extent in milk. No adverse reactions were observed in fed children. Withdrawal from the breast is usually not necessary.

Very common: isolated hyperammonaemia. Common: mild and transient bone marrow suppression, thrombocytopenia, tremor, paresthesia, headache, transient hair loss, hair thinning, irregular menstruation, weight gain, weight loss, increased or decreased appetite. Uncommon: haemorrhage, hyperactivity, irritability, nausea, vomiting, increased salivation, gastrointestinal disturbances, liver dysfunction, sometimes with hyperammonaemia and drowsiness (in children, these disorders can be particularly severe and lead to death), peripheral edema with severe course. Rare: reduction of fibrinogen, systemic lupus erythematosus, Fanconi syndrome, increase in testosterone concentration, nystagmus, dizziness, hyperammonaemia with neurological symptoms, hearing loss, pancreatic function disorders (sometimes fatal), rash, skin vasculitis, erythema multiforme , amenorrhea, polycystic ovary, stomatitis, porphyria. Very rare: bone marrow suppression, sometimes leading to agranulocytosis, anemia or pancytopenia, lymphocytosis, prolonged bleeding time, bedwetting, hallucinations, tinnitus, toxic epidermal necrolysis, Stevens-Johnson syndrome. Not known: there have been reports of decreased bone mineral density, osteopenia and osteoporosis, and fractures in patients using sodium valproate for long-term therapy. In addition, fatigue, apathy, ataxia, confusion, stupor, lethargy passing into transient coma and dementia with reversible atrophy of the brain and transient parkinsonism were observed.

Orally.monotherapy. Initial dose - adults, adolescents, children: 10-15 mg / kg daily in two or more divided doses. The dose should be increased gradually at weekly intervals of 5-10 mg / kg, until the desired therapeutic effect is achieved. Maintenance dose - adults and adolescents: 9-35 mg / kg per day; children: 15-40 mg / kg daily in one dose or two divided doses. Children about the month ofless than 20 kg should receive sodium valproate in a different pharmaceutical form due to the need to adjust the dose of the preparation.Combination therapy. If the preparation is used in combination with previously used medicinal products or is replaced by a previously used medicinal product, a reduction of the previously used preparation (in particular phenobarbital) should be considered to avoid side effects. If the use of the existing preparation is to be discontinued, the withdrawal must be gradual. Since the induction of enzymes by other antiepileptics (such as phenobarbital, phenytoin, primidone and carbamazepine) is transient, 4-6 weeks after the last drug treatment, the valproic acid level in the blood should be measured and if necessary reduced daily dose.
In elderly patients, the pharmacokinetics of the drug may be altered, therefore the dosage should be determined based on the control of seizures. In patients with renal insufficiency, an increase in the free form of valproic acid in the blood should be taken into account and if necessary, the dose should be reduced.Manic episodes in bipolar disorder. Adults: The daily dose should be determined individually. The recommended initial daily dose is 750 mg. In addition, a satisfactory safety profile was obtained in clinical trials at an initial dose of 20 mg / kg. The sustained release dosage forms can be administered 1 or 2 times a day. The dose should be increased as soon as possible to achieve the lowest therapeutic concentration that ensures the desired clinical effect. The average daily dose is usually between 1000 and 2000 mg. Patients receiving daily doses exceeding 45 mg / kg they should remain under close observation.
The preparation should be taken during or after a meal. Swallow the tablets whole, do not chew, crush them, drink plenty of liquid.