Composition, form of production and packaging
Tablets of prolonged action, covered with a film coating of white color, oval, biconcave, with the smell of vanillin, with a fault line and engraving "CC3" on one side; on the bend - white or almost white.
1 tab.
sodium valproate 300 mg
Excipients: citric acid 39 mg, ethyl cellulose 60 mg, methyl methacrylate copolymer, trimethylammonioethyl methacrylate chloride and ethyl acrylate (1: 2: 0.1) (eudragit RS30D) 20.1 mg, talc 8.1 mg, silicon dioxide colloid 6 mg, magnesium stearate - 6 mg.
Composition of the coating: copolymer of methyl methacrylate, trimethylammonioethyl methacrylate chloride and ethyl acrylate (1: 2: 0.2) (Eudragit RL30D type A) 2.25 mg, methyl methacrylate copolymer, trimethylammonioethyl methacrylate chloride and ethyl acrylate (1: 2: 0.1) (2.20 mg), triethyl citrate - 0.9 mg, carmellose sodium - 1.27 mg, titanium dioxide - 1.06 mg, talc - 2.02 mg, vanillin - 0.11 mg.
50 pcs. - vials of polypropylene (1) - packs cardboard.
50 pcs. - bottles of dark glass (1) - packs of cardboard.
100 pieces. - vials of polypropylene (1) - packs cardboard.
100 pieces. - bottles of dark glass (1) - packs of cardboard.
Tablets of prolonged action, covered with a film coating of white color, oval, biconcave, with the smell of vanillin, with a fault line and engraving "CC5" on the one hand; on the bend - white or almost white.
1 tab.
sodium valproate 500 mg
Auxiliary substances: citric acid - 65 mg, ethyl cellulose - 100 mg, copolymer of methyl methacrylate, trimethylammonioethyl methacrylate chloride and ethyl acrylate (1: 2: 0.1) (eudragit RS30D) - 33.5 mg, talc - 13.5 mg, silicon colloidal anhydrous - 10 mg, magnesium stearate - 10 mg.
Composition of the coating: copolymer of methyl methacrylate, trimethylammonioethyl methacrylate chloride and ethyl acrylate (1: 2: 0.2) (Eudragit RL30D type A) 3.2 mg, methyl methacrylate copolymer, trimethylammonioethyl methacrylate chloride and ethyl acrylate (1: 2: 0.1) (3.20 mg), triethyl citrate - 1.28 mg, carmellose sodium - 1.8 mg, titanium dioxide - 1.5 mg, talc - 2.87 mg, vanillin - 0.15 mg.
50 pcs. - vials of polypropylene (1) - packs cardboard.
50 pcs. - bottles of dark glass (1) - packs of cardboard.
100 pieces. - vials of polypropylene (1) - packs cardboard.
100 pieces. - bottles of dark glass (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
PHARMACHOLOGIC EFFECT
Antiepileptic drug. It also has a central muscle relaxant and sedative effect.
The mechanism of action is mainly due to an increase in the GABA content in the CNS due to inhibition of the GABA-transferase enzyme. GABA reduces the excitability and convulsive readiness of the motor zones of the brain. In addition, the action of valproic acid on the GABA A receptors (activation of GABA-ergic transmission), as well as the influence on the potential-dependent sodium channels, plays an important role in the mechanism of action of the drug. According to another hypothesis, it 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 conductivity for potassium ions.
It improves the mental state and mood of patients, has antiarrhythmic activity.
PHARMACOKINETICS
Suction
Valproic acid is almost completely absorbed from the digestive tract, the bioavailability when ingested is 100%. Eating does not reduce the absorption rate. C max in blood plasma is achieved after 4 hours. The therapeutic concentration of valproic acid in blood plasma is 50-150 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 subjected to glucuronidation and oxidation in the liver.
Excretion
Valproic acid (1-3% of the dose) and its metabolites are excreted by the kidneys, small amounts - with feces and exhaled air. T 1/2 valproic acid with monotherapy and in 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, elderly patients and children under the age of 18 months, a significant increase in T 1/2 is possible.
INDICATIONS
- 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 (Vesta, Lennox-Gastaut);
- Behavioral disorders due to epilepsy;
- febrile convulsions in children, children's teak;
- treatment and prevention of bipolar affective disorders, resistant to treatment with lithium drugs or other drugs.
DOSING MODE
Tablets of prolonged action are taken orally, without chewing, 1-2 times / day, during or immediately after eating, with a small amount of water.
Adults are prescribed in an initial dose of 600 mg / day with a gradual increase every 3 days to achieve a clinical effect (disappearance of seizures).
The initial dose for monotherapy is 5-15 mg / kg / day, then gradually increase the dose by 5-10 mg / kg per week.
The recommended daily dose is about 1-2 g, i.Рµ. 20-30 mg / kg. If necessary, the dose may be increased to 2.5 g / day (30 mg / kg / day).
The maximum dose is 30 mg / kg / day (in patients with accelerated metabolism of valproic acid, the maximum dose can be increased to 60 mg / kg / day under the control of the concentration of valproic acid in blood plasma).
When combined therapy, the dose is 10-30 mg / kg / day, followed by an increase of 5-10 mg / kg per week.
Children with a body weight of more than 25 kg are prescribed in an initial dose of 300 mg / day (5-15 mg / kg / day), with a gradual increase of 5-10 mg / kg per week until the clinical effect (disappearance of seizures), while the dose , as a rule, is 1-1.5 g / day (20-30 mg / kg / day).
The maximum dose is 30 mg / kg / day (in patients with accelerated metabolism of valproic acid, the maximum dose can be increased to 60 mg / kg / day under the control of the concentration of valproic acid in blood plasma).
For children weighing 20-25 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. It should be borne in mind that children with a body weight of less than 20 kg are not recommended to use the drug in the form of long-acting tablets, they should use other forms of the drug.
Although the pharmacokinetics of valproic acid in the elderly may have its own peculiarities, this is of limited clinical importance, and the dose should be determined by the clinical effect. Due to a decrease in binding to serum albumin, the proportion of unbound preparation in plasma increases. This causes the expediency of a more careful selection of the dose of the drug in the elderly, with the possible use of smaller doses of the drug.
Patients with renal insufficiency may find it necessary to reduce the dose of the drug. The dose should be selected by monitoring the clinical state, since plasma concentrations may not be sufficiently informative.
SIDE EFFECT
In general, Convulex В® is well tolerated by patients. Side effects are possible mainly at a drug concentration in the plasma above 100 mg / l or with combination therapy.
On the part of the digestive system: nausea, vomiting, gastralgia, decreased 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 CNS: tremor, changes in behavior, mood or mental state (depression, fatigue, hallucinations, aggressiveness, hyperactive state, psychoses, unusual agitation, motor anxiety or irritability), ataxia, dizziness, drowsiness, headache, encephalopathy, dysarthria, enuresis, stupor, impaired consciousness, coma.
From the senses: diplopia, nystagmus, flashing of "flies" before the eyes.
On the part of the hematopoiesis system: anemia, leukopenia, thrombocytopenia, reduction of fibrinogen and platelet aggregation, leading to the development of hypocoagulation (accompanied by prolonged bleeding time, petechial hemorrhages, bruises, bruises, bleeding).
From the side of metabolism: decrease or increase in body weight.
Allergic reactions: skin rash, hives, angioedema, photosensitivity, malignant exudative erythema (Stevens-Johnson syndrome).
On the part of laboratory indicators: hypercreatininaemia, hyperammonemia, hyperbilirubinemia, a slight increase in the activity of hepatic transaminases, LDH (dose-dependent).
On the part of the endocrine system: dysmenorrhea, secondary amenorrhea, breast enlargement, galactorrhea.
Other: peripheral edema, hair loss (usually recovers after drug discontinuation).
CONTRAINDICATIONS
- liver failure;
acute and chronic hepatitis;
- impaired pancreatic function;
- porphyria;
- hemorrhagic diathesis;
- severe thrombocytopenia;
- Disorders of urea metabolism (including in family history);
- lactation period;
- Children weighing less than 20 kg;
- Children's age up to 3 years;
- Hypersensitivity to valproic acid and its salts or components of the drug.
With caution:
- with anamnestic data on liver and pancreas diseases;
- with oppression of bone marrow hematopoiesis (leukopenia, thrombocytopenia, anemia);
- with renal insufficiency;
- with congenital fermentopathy;
- with organic diseases of the brain;
- with hypoproteinemia;
- during pregnancy (especially I trimester);
- children with mental retardation.
PREGNANCY AND LACTATION
During treatment should be protected from pregnancy. In animal experiments, the teratogenic effect of valproic acid has been revealed. The incidence of neural tube defects in children born to women taking valproate in the first trimester of pregnancy is 1-2%. It is advisable in this regard, the use of folic acid preparations. In the first trimester of pregnancy, do not start treatment with Convex. If the pregnant woman is already receiving the drug, then due to the risk of more seizures, treatment should not be interrupted. The drug should be used in the lowest effective doses, avoiding the combination with other anticonvulsants and, if possible, regularly monitoring the concentration of valproic acid in the plasma.
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
In connection with the available reports of severe and lethal cases of hepatic insufficiency and pancreatitis with the use of valproic acid preparations, it is necessary to bear in mind the following:
- At-risk groups are infants and children under 3 years old, with severe epilepsy, often associated with brain damage and congenital metabolic or degenerative diseases;
- in most cases, liver function abnormalities developed in the first 6 months (usually between 2 and 12 weeks) of treatment, more often with combined antiepileptic treatment;
- cases of pancreatitis were observed regardless of the patient's age and duration of treatment, although the risk of developing pancreatitis decreased with the age of the patient;
- Lack of liver function in pancreatitis increases the risk of death;
- early diagnosis (before the icteric stage) is based mainly on clinical observation - the detection of early symptoms such as asthenia, anorexia, extreme fatigue, drowsiness, sometimes accompanied by vomiting and abdominal pain; with the recurrence of epileptic seizures against a background of unchanged antiepileptic therapy.
In such cases, you should immediately consult a doctor for clinical examination and liver function analysis.
During treatment, especially in the first 6 months, it is necessary to periodically check the liver function - the activity of hepatic transaminases, the level of prothrombin, fibrinogen, coagulation factors, bilirubin concentration, and amylase activity (every 3 months, especially when combined with other antiepileptic drugs) and a picture of peripheral blood, in particular, blood platelets.
Patients who receive other antiepileptic drugs, transfer to admission valproic acid should be carried out gradually, reaching a clinically effective dose after 2 weeks, after which a gradual cancellation of other antiepileptic drugs is possible. In patients who were not treated with other antiepileptic drugs, a clinically effective dose should be achieved after 1 week.
The risk of developing side effects from the liver is increased when combined anticonvulsant therapy, as well as in children. Do not drink drinks containing ethanol.
Before the surgical intervention, a general blood test (including platelet numbers), bleeding time, coagulogram indices is required.
If there is a "acute abdomen" symptom complex before treatment, it is recommended to determine the activity of amylase in the blood to exclude acute pancreatitis.
During treatment it is necessary to take into account the possible distortion of the results of urinalysis in diabetes mellitus (due to an increase in the content of ketone bodies), thyroid function indices.
With the development of any acute serious side effects, it is necessary to immediately discuss with the doctor the advisability of continuing or discontinuing treatment.
To reduce the risk of developing dyspeptic phenomena, it is possible to take antispasmodics and enveloping agents.
A sharp discontinuation of the use of Convulex can lead to an increase in epileptic seizures.
Impact on the ability to drive vehicles and manage mechanisms
During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous 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 vital body functions.
DRUG INTERACTION
Valproic acid enhances effects, incl. and secondary, other antiepileptic drugs (phenytoin, lamotrigine), antidepressants, antipsychotic drugs (neuroleptics), anxiolytics, barbiturates, MAO inhibitors, timoleptics, ethanol. The addition of valproic acid to clonazepam in isolated cases can lead to an increase in the expression of absences status.
With the simultaneous use of valproic acid with barbiturates or primidone, there is an increase in the concentration of the latter in the blood plasma.
Increases T 1/2 of lamotrigine (inhibits liver enzymes, slows metabolism of lamotrigine, so that T 1/2 it lengthens to 70 hours in adults and up to 45-55 hours in children).
Reduces zidovudine clearance by 38%, while its T 1/2 does not change.
Tricyclic antidepressants, MAO inhibitors, antipsychotics (antipsychotics) and other drugs that reduce the threshold of seizure activity, reduce the effectiveness of the drug. With simultaneous reception of the preparation of Convulex В® with ethanol and other drugs depressing the work of the central nervous system (tricyclic antidepressants, MAO inhibitors, antipsychotic drugs), it is possible to increase CNS depression.
When combined with salicylates, there is an increase in the effects of valproic acid (displacement of plasma from the protein). Convux В® enhances the effect 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 plasma by 35-50% (dose adjustment is necessary).
Myelotoxic drugs - increased risk of oppression of bone marrow hematopoiesis.
Valproic acid does not induce induction hepatic enzymes and does not reduce the effectiveness of oral contraceptives.
Ethanol and hepatotoxic drugs increase the likelihood of developing liver damage.
Valproic acid can both increase and decrease the concentration of ethosuximide in the blood serum due to changes in metabolism.
Meropenem reduces the concentration of valproic acid in the plasma, which can lead to a decrease in the anticonvulsant effect.
With simultaneous application with topiramate, the risk of hyperammonemia and encephalopathy increases.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in a dry place in tightly closed containers at a temperature of no higher than 25 В° C. Shelf life - 5 years.
