Composition, form of production and packaging
Syrup for children is colorless or slightly yellowish, with a fruity odor.
1 ml
sodium valproate 50 mg
Auxiliary substances: maltitol liquid (lycasin 80/55) - 800 Ојg, methylparahydroxybenzoate - 1 mg, propyl parahydroxybenzoate - 400 Ојg, sodium saccharate - 1 mg, sodium cyclamate - 3 mg, sodium chloride - 400 Ојg, raspberry aroma 9/372710 - 400 mkg, peach flavoring 9/030307 - 1.25 mg, purified water - up to 1 ml.
100 ml - bottles of dark glass (1) complete with a measuring syringe - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
Antiepileptic drug. The mechanism of action is due to inhibition of the enzyme GABA-transferase and an increase in GABA in the CNS. GABA interferes with pre- and postsynaptic discharges and thereby prevents the spread of convulsive activity in the central nervous system. In addition, the action of valproic acid on the GABAA receptors plays an important role in the mechanism of action of the drug, as well as the effect on voltage-dependent sodium channels. According to another hypothesis, valproic acid acts on the sites of postsynaptic receptors, imitating or enhancing the inhibitory effect of GABA. A possible direct effect on membrane activity is associated with changes in potassium permeability.
It improves the mental state and mood of patients, has antiarrhythmic activity.
PHARMACOKINETICS
Suction
Valproic acid is quickly and almost completely absorbed from the digestive tract, bioavailability when ingested is about 100%. Eating does not reduce the absorption rate. C max in plasma is observed after 3-4 hours. The therapeutic concentration of valproic acid in blood plasma is 50-100 mg / l.
The prolonged form is characterized by slow absorption, a lower (by 25%), but more stable plasma concentration between 4 and 14 hours.
Distribution
C ss is achieved on the 2nd-4th day of treatment, depending on the intervals between doses.
At a plasma concentration of up to 50 mg / l, the binding of valproic acid with plasma proteins is 90-95%, with a concentration of 50-100 mg / l, 80-85%.
Values ​​of concentration in the cerebrospinal fluid correlate with the value of the fraction of the active substance not associated with proteins. Valproic acid penetrates the placental barrier, excreted in breast milk. Concentration in breast milk is 1-10% concentration in the blood plasma of the mother.
Metabolism
Valproic acid is metabolized in the liver by oxidation and conjugation with glucuronic acid.
Excretion
Valproic acid (1-3% of the dose) and its metabolites are excreted by the kidneys, in small amounts - with feces and exhaled air. T 1/2 for monotherapy and for healthy volunteers is 8-20 hours.
Pharmacokinetics in special clinical cases
With uremia, hypoproteinemia and cirrhosis, the binding of valproic acid with plasma proteins decreases.
When combined with other drugs T 1/2 can be 6-8 hours due to the induction of metabolic enzymes. In patients with impaired liver function and elderly people, a significant increase in T 1/2 is possible.
In elderly patients due to a reduction in the binding of the active substance to serum albumin, an increase in the plasma content of the unbound preparation is possible.
INDICATIONS
- epilepsy of any genesis;
- epileptic seizures (including generalized and partial, as well as against the background of organic brain diseases);
- behavioral disorders associated with epilepsy;
- febrile convulsions in children;
- Manic-depressive syndrome with bipolar course, not amenable to treatment with lithium preparations or other drugs.
DOSING MODE
Children with a body weight of more than 25 kg are prescribed in an initial dose of 300 mg / day with a gradual increase to achieve a clinical effect (disappearance of seizures), with the dose, as a rule, 20-30 mg / kg / day.
The initial dose for monotherapy is 5-15 mg / kg / day, then the dose is gradually increased by 5-10 mg / kg per week.
The maximum dose is 30 mg / kg / day (can be increased to 60 mg / kg / day under the control of the concentration of valproic acid in blood plasma).
For children weighing 7.5-25 kg with monotherapy, the average dose is 15-45 mg / kg / day, the maximum - 50 mg / kg / day. When combined therapy - 30-100 mg / kg / day.
The average dose of Convulex is shown in the table.
Body weight of the patient (kg) Dose (mg / day) Quantity of syrup (ml)
7.5-14 150-450 3-9
14-21 300-600 6-12
21-32 600-900 12-18
32-50 900-1500 -
50-90 1500-2500 -
Patients with renal insufficiency may need to reduce the dose of the drug. The dose is set by monitoring the clinical state of the patient, tk. Valence concentrations of valproic acid in blood plasma may not be enough informative.
The daily dose of the drug is divided into 2-3 doses. The drug is taken regardless of food intake.
The syrup is taken with a small amount of liquid.
SIDE EFFECT
The development of side effects is possible mainly at a drug concentration in the blood plasma of more than 100 mg / kg or with combined therapy.
On the part of the digestive system: nausea, vomiting, gastralgia, anorexia or increased appetite, diarrhea, hepatitis; rarely - constipation, pancreatitis, up to severe lesions with a lethal outcome (in the first 6 months of treatment, more often for 2-12 weeks).
From the side of the central nervous system: there is a tremor, diplopia, nystagmus, flashing of "flies" before the eyes; rarely changes in behavior, mood or mental state (depression, fatigue, hallucinations, aggressiveness, hyperactive state, psychoses, unusual arousal, motor anxiety or irritability), ataxia, dizziness, drowsiness, headache, dysarthria, stupor, impaired consciousness, coma .
On the part of the hematopoiesis system: anemia, leukopenia, thrombocytopenia, fibrinogen reduction, platelet aggregation and blood coagulation, accompanied by prolonged bleeding time, petechial hemorrhages, bruising, bruising, bleeding.
From the side of metabolism: it is possible to reduce or increase body weight.
From the endocrine system: possible dysmenorrhea, secondary amenorrhea, breast enlargement, galactorrhea.
On the part of laboratory indicators: hypercreatininaemia, hyperammonemia, hyperbilirubinemia, a slight increase in the activity of hepatic transaminases, LDH (dose-dependent).
Allergic reactions: skin rash, hives, angioedema, photosensitivity, Stevens-Johnson syndrome are possible.
Other: swelling, hair loss (usually recovers after drug discontinuation).
Side effects are possible mainly at the level of valproic acid in blood plasma above 100 mg / l or with combined therapy.
CONTRAINDICATIONS
severe hepatic impairment;
- severe disorders of the pancreas;
- porphyria;
- hemorrhagic diathesis;
- severe thrombocytopenia;
- I trimester of pregnancy;
- lactation (breastfeeding);
- Hypersensitivity to valproic acid.
With special caution should prescribe the drug with an indication in the history of liver disease and pancreas, lesions of the bone marrow; with violations of kidney function; patients with congenital enzymopathy; mentally retarded children; with organic brain lesions; with hypoproteinemia.
PREGNANCY AND LACTATION
Convullex В® is contraindicated for use in the first trimester of pregnancy.
With the onset of pregnancy due to the risk of deterioration of treatment should not be interrupted. Convullex В® should be used in the lowest effective doses, avoid combination with other anticonvulsants and regularly monitor the level of valproic acid in the plasma.
If you need to use Convulex during lactation, you should decide whether to stop breastfeeding.
Women of childbearing age in the period of treatment should apply reliable methods of contraception.
In experimental studies , the teratogenic effect of the drug was established.
The incidence of neural tube defects in children born to women taking valproate in the first trimester of pregnancy is 1-2%. In this regard, in pregnancy, it is advisable to use folic acid preparations.
APPLICATION FOR FUNCTIONS OF THE LIVER
Patients with renal insufficiency may need to reduce the dose of the drug. The dose is set by monitoring the clinical state of the patient, tk. Valence concentrations of valproic acid in blood plasma may not be enough informative.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in severe violations of liver function. With extreme caution, you should prescribe the drug with a history of liver disease.
APPLICATION FOR CHILDREN
Contraindication: children under 3 years (for tablets with prolonged action).
SPECIAL INSTRUCTIONS
Patients who receive other antiepileptic drugs, the transfer to the treatment of Convulex should be carried out gradually, reaching a clinically effective dose after 2 weeks, after which a gradual cancellation of other antiepileptic agents is possible. In patients who have not been treated with other antiepileptic drugs, a clinically effective dose should be achieved after 1 week of therapy.
When combined anticonvulsant therapy is used, the risk of side effects from the liver is increased.
In patients receiving Convulex В® , a general blood test (including the number of platelets), bleeding time, coagulogram indices is required before surgery.
If a symptom-complex "acute abdomen" occurs before the onset of surgery, it is recommended to determine the level of amylase in the blood to exclude acute pancreatitis.
It should be borne in mind that against the background of treatment may distort the results of urinalysis in diabetes mellitus (due to an increase in the content of keto products), indicators of thyroid function.
To reduce the risk of developing dyspeptic phenomena, it is possible to take antispasmodics and enveloping agents.
The patient should be warned about the need to consult a doctor about the advisability of continuing or discontinuing treatment for the development of any acute serious side effects.
A sharp discontinuation of the use of Convulex can lead to more frequent seizures.
During the period of drug use, alcohol should be avoided.
Control of laboratory indicators
Before the start of therapy and during the use of the drug, it is necessary to regularly monitor liver function (hepatic transaminase activity, bilirubin content), the peripheral blood picture, the state of the blood coagulation system, the activity of amylase (every 3 months, especially when combined with other antiepileptic drugs).
Use in Pediatrics
When using the drug in children, the risk of side effects from the liver increases.
Impact on the ability to drive vehicles and manage mechanisms
Patients taking Convullex В® should refrain from engaging in potentially dangerous activities requiring increased attention and speed of psychomotor reactions.
OVERDOSE
Symptoms: nausea, vomiting, dizziness, diarrhea, impaired breathing function, muscle hypotension, hyporeflexia, miosis, coma.
Treatment: gastric lavage (not later than 10-12 hours) followed by the appointment of activated charcoal, hemodialysis. Forced diuresis, maintenance of respiratory function and cardiovascular system.
DRUG INTERACTION
Pharmacodynamic interaction
With the simultaneous use of valproic acid with drugs that exert a depressing effect on the central nervous system (including tricyclic antidepressants, MAO inhibitors and antipsychotic drugs), as well as with ethanol, an increase in the CNS depression is possible.
Hepatotoxic drugs (including ethanol) increase the likelihood of liver damage.
Drugs that reduce the threshold of convulsive readiness (including tricyclic antidepressants, MAO inhibitors, antipsychotics), reduce the effectiveness of valproic acid.
Convullex В® enhances the effects (including side effects) of other anticonvulsants (phenytoin, lamotrigine), antidepressants, antipsychotics, tranquilizers, barbiturates, MAO inhibitors, thymoleptics, ethanol. With the use of valproate in patients receiving clonazepam, in isolated cases there was an increase in the expression of absent status.
Pharmacokinetic interaction
With the simultaneous use of valproic acid with barbiturates or with primidone, there is an increase in their concentrations in the blood plasma. Due to the inhibition of liver enzymes under the influence of valproic acid and lamotrigine metabolism retardation, its T 1/2 increase to 70 h in adults and to 45-55 h in children.
Valproic acid reduces zidovudine clearance by 38%, while its T 1/2 does not change.
With simultaneous application with salicylates, the effects of valproic acid are enhanced due to its displacement from the bond with plasma proteins. Convullex В®enhances the effects of antiplatelet agents (acetylsalicylic acid) and indirect anticoagulants.
When combined with phenobarbital, phenytoin, carbamazepine, mefloquine, the content of valproic acid in the blood serum decreases (acceleration of metabolism).
Felbamate increases the concentration of valproic acid in the blood plasma by 35-50% (dose adjustment is necessary).
Valproic acid does not induce the induction of hepatic enzymes and does not reduce the effectiveness of oral contraceptives.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. Keep in a dry, dark place at a temperature of 15 В° to 25 В° C. Shelf life - 5 years ..
