Index of drugs

Epileptic conditions in which intravenously administered benzodiazepines are ineffective. Group fits. Treatment of convulsive seizures when oral treatment is temporarily impossible, due to the state of consciousness or inability to swallow, especially if the patient was previously successfully treated orally with sodium valproate (for generalized and partial seizures). Prophylactically in connection with head neurosurgical procedures, when there is a possibility of epileptic seizures.

1 vial of powder contains 400 mg sodium valproate.

Anticonvulsant. Increases the concentration of gamma-aminobutyric acid (GABA) in the brain. T_0,5 is 15-17 h. The minimum serum concentrations necessary to achieve therapeutic efficacy is 40-50 mg / l, in a wide range between 40 and 100 mg / l. If the concentration exceeds 200 mg / l, the dose should be reduced. Steady state concentrations are achieved within 2-4 days. Valproate binds to plasma proteins to a very large extent. It is metabolized by beta-ultaining and conjugated with glucuronic acid. It is mainly excreted in the urine.

Hypersensitivity to sodium valproate or other components of the drug. acute and chronic hepatitis. Severe hepatitis (especially drug-induced) in a history or a family history. Porphyria. Simultaneous treatment with mefloquine.

Due to the risk of severe hepatic impairment that may be fatal, the need for the preparation should be carefully considered in infants and children under 3 years of age, especially with severe epilepsy and in combination with brain damage, delayed psychomotor development and (or ) metabolic or genetic degenerative disease. In children under the age of 3 years, the preparation should be administered as monotherapy and only if the benefit outweighs the risk of liver damage and pancreatitis; in children of this age, concomitant use of salicylates should be avoided due to the risk of liver toxicity. In children over 3 years, the risk of liver damage decreases with age. The preparation may cause severe pancreatitis, sometimes fatal, especially in young children; the risk decreases with age. Risk factors are severe seizures, neurological disorders and the use of several antiepileptic drugs at the same time. Hepatic failure combined with pancreatitis increases the risk of death. The use of valproate is not recommended in patients with deficiency of urea cycle enzymes. Particularly cautiously used in patients with impaired renal function (may need to reduce the dose of the drug) and with systemic lupus erythematosus. An immediate discontinuation of treatment should be considered if signs of liver and / or pancreatic injury occur and / or abnormal prothrombin time is detected, especially if other abnormalities are present in the test results. There have been reports of suicidal ideation and suicidal behavior in patients taking anti-epileptic drugs - patients undergoing treatment should be under permanent medical supervision. Co-administration of valproate and carbapenems is not recommended.

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. The decision about breastfeeding should be made after assessing all the facts.

Common: nausea, stomach pain, diarrhea (at the beginning of treatment, usually lasting a few days), thrombocytopenia, isolated and moderate increases in blood ammonia (no change in liver function tests, no interruption of treatment), transient and / or dependent from the dose of the drug hair loss. Uncommon: ataxia. Rare: liver damage, anemia, leukopenia, pancytopenia, hearing loss. Very rare: pancreatitis (sometimes fatal), hyponatremia, transient dementia (associated with transient atrophy of the brain), toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, involuntary urination, peripheral edema of moderate intensity. In individual cases: stupor or lethargy (sometimes causing transient coma, more frequent in patients taking several antiepileptic drugs simultaneously, especially phenobarbital or topiramate or after a sudden increase in valproate dose), transient Fanconi syndrome. In addition: a syndrome of maladjusted anti-diuretic hormone (SIADH), sedation, extrapyramidal disorder (including transient parkinsonian symptoms), transient and / or dose-dependent postural tremor and drowsiness, increased blood ammonia with neurological symptoms, bone marrow failure ( including red cell aplasia), agranulocytosis, isolated reduction of fibrinogen and prolonged bleeding time, skin reactions (eg rash), amenorrhea, irregular menstrual cycles, male infertility, vasculitis, angioneurotic edema, severe hypersensitivity syndrome with drug erosion with eosinophilia and general symptoms (DRESS), allergic reactions, weight gain, confusion. Nausea may occur after intravenous administration, which disappears spontaneously after a few minutes.

Intravenously. The daily dose should be determined depending on age and body weight. The basis for determining the optimal dose of the preparation should always be clinical efficacy. Determination of the concentration of a drug in the blood is of secondary importance and should be performed in the case of insufficient control of seizures or suspected adverse reactions. The concentration of effective valproate in the blood serum is usually 50-120 mg / l (375-840 μmol / l). In patients who have previously been successfully treated with the oral formulation, the current dose can be given by continuous intravenous infusion or by multiple injections. For the remaining patients, the drug may be given initially by slow intravenous injection (over 3 min), usually 15 mg / kg, and then continued as an intravenous infusion at a rate of usually 1-2 mg / kg / h, adjusting it to the clinical response. Studies show that the results are not influenced by gender, duration of injection, previous use of another anti-epileptic medicine or previous dose of valproic acid between 5.3-28 mg / kg / day. As soon as possible, treatment should be continued with the oral preparation at generally recommended doses.
The solution should be prepared immediately prior to administration and used within 24 hours. With simultaneous administration of other drugs, the preparation should be administered through a separate catheter.