pharmachologic effect
Antiepileptic drug. It also has a central muscle relaxant and sedative effect.
The mechanism of action is due mainly to an increase in the content of gamma-aminobutyric acid (GABA) in the CNS due to inhibition of the GABA transferase enzyme. GABA reduces the excitability and convulsive readiness of the motor areas of the brain. In addition, in the mechanism of action of the drug, a significant role belongs to the effect of valproic acid on GABAА receptors (activation of GABA-ergic transmission), as well as the effect on voltage-dependent sodium channels. According to another hypothesis, it acts on sites of postsynaptic receptors, mimicking or enhancing the inhibitory effect of GABA. A possible direct effect on membrane activity is associated with changes in the conductivity for potassium ions.
Improves the mental state and mood of patients, has antiarrhythmic activity.
Pharmacokinetics
Distribution
Css with intravenous administration is achieved within a few minutes and can be maintained with a slow infusion. The therapeutic concentration of the drug in blood plasma ranges from 50-150 mg / l.
Valproic acid binds to plasma proteins by 90-95% at plasma concentrations up to 50 mg/l and by 80-85% at concentrations of 50-100 mg/l.
Valproic acid crosses the BBB. Cerebrospinal fluid concentration levels correlate with the protein-free fraction of the drug, accounting for about 10% of the serum level. Valproic acid crosses the placental barrier and is excreted in breast milk. The concentration in breast milk is 1-10% of the concentration in the mother’s blood plasma.
Metabolism and excretion
The drug undergoes glucuronidation and oxidation in the liver.
Metabolites and unchanged valproic acid (1-3% of the dose) are excreted by the kidneys, small amounts are excreted in the feces and exhaled air. T1 / 2 of the drug is in healthy volunteers and with monotherapy from 8 to 20 hours.
Pharmacokinetics in special clinical situations
With uremia, hypoproteinemia and cirrhosis, protein binding is reduced.
When combined with other drugs, T1 / 2 may be 6-8 hours due to the induction of metabolic enzymes.
In patients with impaired liver function, elderly patients and children under 18 months T1 / 2 may be significantly longer.
Indications of the drug Konvuleks®
epileptic status;
epilepsy of various etiologies (idiopathic, cryptogenic and symptomatic);
generalized epileptic seizures in adults and children (clonic, tonic, tonic-clonic, absences, myoclonic, atonic);
partial epileptic seizures in adults and children (with or without secondary generalization);
specific syndromes (West, Lennox-Gastaut);
febrile convulsions in children;
treatment and prevention of bipolar affective disorders.Dosing regimen
The drug is used for intravenous administration.
With intravenous slow administration, the recommended daily dose is 5-10 mg/kg of body weight. With intravenous infusion, the recommended dose is 0.5-1 mg / kg / h.
When switching from oral to intravenous administration, the doses do not change, the first intravenous administration is recommended 12 hours after the last oral administration. The introduction of the solution for injection should be replaced by taking the drug orally, as soon as the patient’s condition allows it. The first oral administration is also recommended 12 hours after the last injection.
If it is necessary to quickly achieve and maintain high plasma concentrations, the following approach is recommended: IV administration of 15 mg/kg over 5 minutes, after 30 minutes, start infusion at a rate of 1 mg/kg/h with constant monitoring of the concentration until a plasma concentration of about 75 mcg/ml.
The maximum daily dose of the drug should not exceed 2500 mg.
Average daily doses are 20 mg/kg in adults and elderly patients, 25 mg/kg in adolescents, 30 mg/kg in children.
As an infusion solution for Konvuleks®, an isotonic sodium chloride solution, 5% dextrose solution, Ringer’s solution are used. The prepared solution for infusion may need to be used within 24 hours, the unused volume of the solution is destroyed. If other drugs are also used intravenously, Convulex® should be administered through a separate infusion system.
Side effect
In general, Convulex® s is well tolerated by patients. Side effects are possible mainly at a concentration of valproic acid in the blood plasma above 100 mg / l or with combined therapy.
On the part of the digestive system: nausea, vomiting, gastralgia, decreased or increased appetite, diarrhea, hepatitis, constipation, pancreatitis, up to severe lesions with a fatal outcome (in the first 6 months of treatment, more often at 2-12 weeks).
From the side of the central nervous system: tremor, changes in behavior, mood or mental state (depression, fatigue, hallucinations, aggressiveness, hyperactivity, psychosis, unusual agitation, restlessness or irritability), ataxia, dizziness, drowsiness, headache, dysarthria, stupor, impaired consciousness, coma.
On the part of the organ of vision: diplopia, nystagmus, flashing “flies” before the eyes.
On the part of the hematopoietic system: anemia, leukopenia, thrombocytopenia, a decrease in the content of fibrinogen, platelet aggregation and blood clotting, accompanied by an increase in bleeding time, petechial hemorrhages, bruising, hematomas, bleeding.
From the genital organs and mammary gland: dysmenorrhea, secondary amenorrhea, breast enlargement, galactorrhea.
On the part of laboratory parameters: hypercreatininemia, hyperammonemia, hyperbilirubinemia, a slight increase in liver transaminases, LDH (dose-dependent).
Allergic reactions: skin rash, urticaria, angioedema, photosensitivity, Stevens-Johnson syndrome.
Other: decrease or increase in body weight, peripheral edema, hair loss (usually recovers after discontinuation of the drug).
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