Mechanism of action
Antiepileptic drug. The mechanism of action is due to inhibition of the GABA transferase enzyme and an increase in the content of GABA in the central nervous system. GABA prevents pre- and postsynaptic discharges and, thereby, prevents the spread of seizure activity in the central nervous system.
Suction
Valproic acid is rapidly and almost completely absorbed from the gastrointestinal tract, bioavailability when administered is about 93%. Eating does not affect the amount of absorption. Cmax in plasma it is noted in 1-3 hours (when taking capsules - in 2-3 hours). The therapeutic concentration of valproic acid in the blood plasma is 50-100 mg / l.
Distribution
Css is achieved by 2-4 days of treatment, depending on the intervals between doses of doses. Plasma protein binding is 80-95%. Concentration levels in the cerebrospinal fluid correlate with the amount of the active substance bound to the proteins. Valproic acid penetrates the placental barrier, excreted in breast milk.
Metabolism
Valproic acid is metabolized by glucuronidation and oxidation in the liver.
Removal
Valproic acid (1-3% of the dose) and its metabolites are excreted by the kidneys. T1/2 with monotherapy and in healthy volunteers is 8-20 hours
Pharmacokinetics in special clinical situations
When combined with other drugs T1/2 may be 6-8 hours due to induction of metabolic enzymes.
Indications and usage
- generalized epileptic seizures;
- small epileptic seizures;
- focal (partial) seizures with simple and complex symptoms;
- convulsive syndrome in organic brain diseases;
- behavioral disorders associated with epilepsy;
- febrile convulsions in children;
- children's tick.
The initial daily dose is 15 mg / kg body weight; the dose is gradually increased by 5-10 mg / kg of body weight per week until the clinical effect is achieved (the disappearance of convulsive seizures).
The average daily dose is 30 mg / kg body weight.
| The body weight of the patient (kg) | Dose (mg / day) | The number of syrup (ml) | Number of drops |
|---|
| 7.5-14 |
150-450 |
3-9 |
15-45 |
| 14-21 |
300-600 |
6-12 |
30-60 |
| 21-32 |
600-900 |
12-18 |
60-90 |
| 32-50 |
900-1500 |
- |
- |
| 50-90 |
1500-2500 |
- |
- |
The daily dose is divided into 2-3 doses.
Capsules accept, without chewing, in time or after food with a small amount of liquid.
The drops are mixed with sweetened water and taken during or after meals.
Syrup for children take during or after a meal, washed down with a small amount of liquid.
Adverse reactions
Gastrointestinal: nausea, vomiting, anorexia (mainly at the beginning of treatment; disappear when the dose is adjusted and the drug is taken during or after a meal); possible violations of the liver and pancreas, increased appetite, pain and cramps in the stomach, diarrhea, constipation.
From the side of the central nervous system: lethargy, ataxia, tremor, dizziness, depression, confusion.
Hemic and lymphatic: rarely - thrombocytopenia, neutropenia, hypofibrinogenemia, anemia.
Allergic reactions: skin rash.
Other: weight gain is possible; rarely - alopecia, lengthening of bleeding time, tendency to petechiae and hematomas, menstrual disorders.
Side effects are possible mainly at the level of valproic acid in the blood plasma above 100 mg / l or with combination therapy.
Contraindications
- abnormal liver function;
- dysfunction of the pancreas;
- hemorrhagic diathesis;
- I trimester of pregnancy;
- lactation (breastfeeding);
- Hypersensitivity to valproic acid.
Pregnancy and breastfeeding
Konvulex is contraindicated for use in the first trimester of pregnancy.
When a pregnancy occurs during therapy, it is recommended to interrupt it. If pregnancy is preserved due to the risk of deterioration, treatment is not recommended. Convulex should be used in the lowest effective doses, to avoid combination with other anticonvulsants, and regularly monitor the level of valproic acid in the plasma.
If necessary, the use of Convulex during lactation should decide on the termination of breastfeeding.
Women of childbearing age should use reliable methods of contraception.
AT experimental studies established teratogenic effect of the drug.
Special notes
With caution prescribed Konvulex with impaired renal function, congenital enzymopathies, severe forms of convulsive seizures, organic brain damage, disorders of the hematopoietic system, patients with liver disease and pancreas history (due to the high risk of liver damage).
Abrupt discontinuation of Convulex may lead to more frequent convulsive seizures.
During the period of use of the drug should avoid alcohol.
Control of laboratory parameters
Before starting therapy and during the period of use of the drug, it is necessary to regularly monitor liver function, the state of the blood coagulation system, the levels of amylase, lipase, plasma nitrogen, kidney function and, if possible, monitor the concentration of valproic acid (and other anticonvulsants) in the blood plasma, with their combined use.
Use in pediatrics
Caution is prescribed Convulex. mentally retarded children and children under the age of 2 (due to the high risk of liver damage).
Influence on ability to drive motor transport and control mechanisms
Patients taking Convulex should refrain from engaging in potentially hazardous activities that require increased attention and quickness of psychomotor reactions.
Overdosage
Symptoms: coma, accompanied by hypo- or areflexia, respiratory depression.
Treatment: gastric lavage followed by the appointment of Activated carbon, hemodialysis. Ensuring diuresis, maintaining the function of respiration and the cardiovascular system.
Drug Interactions
With simultaneous use Konvulex potentiates the inhibitory effect on the central nervous system of neuroleptics, antidepressants and ethanol, and also enhances the effect of antiplatelet agents (acetylsalicylic acid) and anticoagulants.
At simultaneous use with Konvulex, salicylates, displacing valproic acid from its association with proteins, enhance the effect of the drug.
With the simultaneous use of Konvulex displaces phenytoin, phenobarbital and diazepam from the association with plasma proteins and increases their free concentration in the blood plasma.
With simultaneous use with Konvulex, phenytoin, phenobarbital, Carbamazepine and primidone increase metabolism and, thus, reduce the level of valproic acid in plasma.
Storage conditions
The drug should be stored in a dry, dark place at a temperature of from 15 ° to 25 ° C. Shelf life - 5 years.
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