Convulex: instructions for use of syrup, drops, solution, tablets and capsules. Varieties, names, composition and release forms of Convulex. Side effects of "Convulex", unwanted reactions

Registration number: P N015315/01

Trade name of the drug: Convulex®

International Nonproprietary Name (INN):
valproic acid

Dosage form: Long-acting, film-coated tablets.

Compound: One tablet contains: active substance - sodium valproate 300 mg or 500 mg; excipients: citric acid - 39.0/65.0 mg, ethylcellulose - 60.0/100.0 mg, methyl methacrylate trimethylammonioethyl methacrylate chloride, ethyl acrylate copolymer (1: 2: 0.1) (Eudragit RS30D) - 20.1/ 33.5 mg, talc - 8.1/13.5 mg, colloidal silicon dioxide - 6.0/10.0 mg, magnesium stearate - 6.0/10.0 mg; shell: methyl methacrylate trimethylammonioethyl methacrylate chloride, ethyl acrylate copolymer (1: 2: 0.2) (Eudragite RL30D type A) - 2.25/3.2 mg, methyl methacrylate trimethylammonioethyl methacrylate chloride, ethyl acrylate copolymer (1: 2: 0.1) (Eudragite RS30D) - 2.25/3.2 mg, triethyl citrate - 0.9/1.28 mg, carmellose sodium - 1.27/1.8 mg, titanium dioxide - 1.06/1.5 mg, talc - 2 .02/2.87 mg, vanillin - 0.11/0.15 mg.

Description. Oval, biconvex, white, film-coated tablets, with a break line and engraving “CC3” (for 300 mg tablets) and “CC5” (for 500 mg tablets) on one side, with the smell of vanillin. At the break: white or almost white.

Pharmacotherapeutic group:
Antiepileptic drug.

ATX code: N03AG01

Pharmachologic effect.

CONVULEX® is an antiepileptic drug that has a central muscle relaxant and sedative effect. The mechanism of action is primarily due to an increase in the content of gamma-aminobutyric acid (GABA) in the central nervous system (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 is played by the effect of valproic acid on GABA A receptors, as well as the effect on voltage-gated sodium channels. According to another hypothesis, it acts on sites of postsynaptic receptors, simulating or enhancing the inhibitory effect of GABA. A possible direct effect on membrane activity is associated with changes in conductivity for potassium ions. Improves the mental state and mood of patients, has antiarrhythmic activity.

Pharmacokinetics. Valproic acid is almost completely absorbed from the gastrointestinal tract, bioavailability when taken orally is 100%. Eating does not reduce the rate of absorption. The maximum level of plasma concentration is observed 4 hours after taking the extended-release tablets. Equilibrium concentration is achieved on days 2-4 of treatment, depending on the intervals between doses. The therapeutic concentration of the drug in blood plasma ranges from 50-150 mg/l. Communication with plasma proteins is 90-95% at a concentration in blood plasma up to 50 mg/l and 80-85% at a concentration of 50-100 mg/l. With uremia, hypoproteinemia and liver cirrhosis, binding to plasma proteins is reduced.
The concentration in the cerebrospinal fluid correlates with the size of the non-protein-bound fraction of the drug. Valproic acid penetrates the placental barrier and the blood-brain barrier and is excreted in breast milk. The concentration in breast milk is 1-10% of the concentration in maternal blood plasma. 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 feces and exhaled air. The half-life (T1/2) of the drug is in healthy subjects and in monotherapy from 8 to 20 hours, when combined with drugs that induce enzymes involved in the metabolism of valproic acid, T1/2 can be 6-8 hours, in patients with disorders liver function in elderly patients and children under 18 months may be significantly longer.
The prolonged form is characterized by slow absorption, lower (25%), but relatively more stable concentrations between 4 and 14 hours.

Indications for use

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 (Vest, Lennox-Gastaut).
Disorders of character and behavior caused by epilepsy.
Febrile convulsions in children, childhood tics
Bipolar affective disorders that cannot be treated with lithium or other medications - treatment and prevention.

Contraindications

Hypersensitivity to valproic acid and its salts or components of the drug
Liver failure
Acute and chronic hepatitis
Pancreatic dysfunction
Porphyria
Hemorrhagic diathesis
Severe thrombocytopenia
Disorders of urea metabolism (including family history)
Lactation period
Children weighing less than 20 kg
Children's age up to 3 years

Carefully:
Prescription of CONVULEX® to the following categories of patients:
- with anamnestic data on diseases of the liver and pancreas
- with inhibition of bone marrow hematopoiesis (leukopenia, thrombocytopenia, anemia);
- with renal failure;
- with congenital enzymopathies;
- children with mental retardation;
- with organic brain diseases;
- with hypoproteinemia;
- pregnancy (especially the first trimester)

Method of administration and dose. CONVULEX® is taken orally, without chewing, 1-2 times a day, during or immediately after meals, with a small amount of liquid.
The initial daily dose is 600 mg, with a gradual increase by 150-250 mg every three days until a clinical effect is achieved (disappearance of seizures).
The initial dose for monotherapy is 5-15 mg/kg/day, then this dose is gradually increased by 5-10 mg/kg/week.
The recommended daily dose is about 1000-2000 mg, i.e. 20-25 mg/kg, if necessary, the dose can be increased to a maximum dose of 2500 mg per day (30 mg/kg body weight). The maximum dose is 30 mg/kg/day (in patients with accelerated metabolism of valproic acid, identified by monitoring the concentration of the drug in the blood plasma, the maximum dose can be increased to 60 mg/kg/day). With combination therapy - 10-30 mg/kg/day, followed by an increase of 5-10 mg/kg/week.

The initial daily dose is 300 mg (5-15 mg/kg/day), with a gradual increase in dose (by 5-10 mg/kg/week) until a clinical effect is achieved (disappearance of seizures), which is usually 1000-1500 mg per day (20-30 mg/kg/day). The maximum dose is 30 mg/kg/day (in patients with accelerated metabolism of valproic acid, identified by monitoring the concentration of the drug in the blood plasma, the maximum dose can be increased to 60 mg/kg/day).

The average daily dose for monotherapy is 15-45 mg/kg, the maximum is 50 mg/kg. With combination therapy - 30-100 mg/kg/day. Children weighing less than 20 kg should be recommended to take other forms of the drug.

Although the pharmacokinetics of valproic acid may vary in the elderly, this is of limited clinical significance and dosing should be based on clinical effect. Due to decreased binding to serum albumin, the proportion of unbound drug in plasma increases. This makes it advisable to more carefully select the dose of the drug in the elderly, with the possible use of smaller doses of the drug.

It may be necessary to reduce the dose of the drug. The dose should be selected based on monitoring of the clinical condition, since plasma concentrations may not be sufficiently informative.

Side effects. In general, CONVULEX® is well tolerated by patients. Side effects are possible mainly when the drug concentration in plasma is above 100 mg/l or during combination therapy.

nausea, vomiting, gastralgia, decreased or increased appetite, diarrhea, hepatitis; rarely constipation, pancreatitis, up to severe injuries with a fatal outcome (in the first 6 months of treatment, more often at 2-12 weeks).

tremor, changes in behavior, mood or mental state (depression, feeling tired, hallucinations, aggressiveness, hyperactivity, psychosis, unusual agitation, restlessness or irritability), ataxia, dizziness, drowsiness, headache, encephalopathy, dysarthria, enuresis, stupor, disturbance of consciousness, coma.

diplopia, nystagmus, flashing “spots” before the eyes.

anemia, leukopenia, thrombocytopenia, decreased fibrinogen content and platelet aggregation, leading to the development of hypocoagulation (accompanied by prolongation of bleeding time, petechial hemorrhages, bruises, hematomas, bleeding).

decrease or increase in body weight.

skin rash, urticaria, angioedema, photosensitivity, malignant exudative erythema (Stevens-Johnson syndrome).

Hypercreatininemia, hyperammonemia, hyperbilirubinemia, slight increase in the activity of liver transaminases, lactate dehydrogenase (dose-dependent).

dysmenorrhea, secondary amenorrhea, breast enlargement, galactorrhea.

peripheral edema, hair loss (usually restored after discontinuation of the drug).

Overdose. Symptoms: nausea, vomiting, dizziness, diarrhea, respiratory dysfunction, muscle hypotonia, hyporeflexia, miosis, coma. Treatment: gastric lavage (no later than 10-12 hours), taking activated carbon, hemodialysis, forced diuresis, maintaining vital body functions.

Interaction

Valproic acid enhances the effects, including side effects, of other antiepileptic drugs (phenytoin, lamotrilzine), antidepressants, antipsychotic drugs (neuroleptics), anxiolytics, barbiturates, monoamine oxidase inhibitors (MAOIs), thymoleptics, ethanol. The addition of valproic acid to clonazepam in isolated cases can lead to increased severity of absence status.
With simultaneous use of valproic acid with barbiturates or primidone, an increase in the concentration of the latter in the blood plasma is observed. Increases T1/2 of lamotrigine (inhibits liver enzymes, causes a slowdown in the metabolism of lamotrigine, as a result of which T1/2 is extended to 70 hours in adults and up to 45-55 hours in children).
Tricyclic antidepressants, MAO inhibitors, antipsychotics (neuroleptics) and other drugs that lower the threshold for seizure activity reduce the effectiveness of the drug. When taking the drug Convulex® simultaneously with ethanol and other drugs that depress the central nervous system (tricyclic antidepressants, MAO inhibitors, antipsychotic drugs), increased depression of the central nervous system is possible.
When combined with salicylates, an increase in the effects of valproic acid is observed (displacement from plasma proteins). Konvulex® 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 plasma by 35-50% (dose adjustment is necessary).

Myelotoxic drugs - increased risk of inhibition of bone marrow hematopoiesis.
Valproic acid does not induce liver enzymes and does not reduce the effectiveness of oral contraceptives.
Ethanol and hepatotoxic drugs increase the likelihood of developing liver damage.
Valproic acid can either increase or decrease the serum concentration of ethosuximide due to changes in metabolism.
Meropenem reduces plasma concentrations of valproic acid, which may result in decreased anticonvulsant effect. When used simultaneously with topiramate, the risk of developing hyperammonemia and encephalopathy increases.

Special instructions. During treatment, it is advisable to monitor the activity of liver transaminases, bilirubin concentration, peripheral blood patterns, blood platelets, the state of the blood coagulation system, amylase activity (every 3 months, especially when combined with other antiepileptic drugs).
For patients receiving other antiepileptic drugs, transfer to valproic acid should be done gradually, reaching a clinically effective dose after 2 weeks, after which gradual withdrawal of other antiepileptic drugs is possible. In patients not treated with other antiepileptic drugs, a clinically effective dose should be achieved after 1 week.
The risk of side effects from the liver is increased during combination anticonvulsant therapy, as well as in children.
Drinks containing ethanol are not allowed.
Before surgery, a general blood test (including platelet count), determination of bleeding time, and coagulogram parameters are required.
If symptoms of an “acute” abdomen occur during treatment, before surgery, it is recommended to determine the activity of amylase in the blood to exclude acute pancreatitis.
During treatment, one should take into account the possible distortion of the results of urine tests in diabetes mellitus (due to an increase in the content of keto products) and indicators of thyroid function.
If any acute serious side effects develop, you should immediately discuss with your doctor the advisability of continuing or stopping treatment.
To reduce the risk of developing dyspeptic disorders, it is possible to take antispasmodics and enveloping agents.
Abruptly stopping CONVULEX® may lead to an increase in epileptic seizures.
During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Release form.
Extended-release film-coated tablets 300 mg and 500 mg.
50 or 100 tablets in a dark glass bottle, hydrolytic resistance type III (Eur.F.), with a white high-density polyethylene cap, with or without a drying capsule built into the cap, with tamper evident. 1 bottle along with instructions for use in a cardboard box.
50 or 100 tablets in a cylindrical container (bottle) made of high-density polyethylene, white, with a lid made of low-density polyethylene with first-opening control. 1 bottle along with instructions for use in a cardboard box.
50 or 100 tablets in a cylindrical container (bottle) made of polypropylene, with a low-density polyethylene cap with tamper evident, with or without a drying capsule built into the cap. 1 bottle along with instructions for use in a cardboard box.

In this article you can read the instructions for use of the drug Convulex. Reviews of site visitors - consumers of this medicine, as well as the opinions of specialist doctors on the use of Convulex in their practice are presented. We kindly ask you to actively add your reviews about the drug: whether the medicine helped or did not help get rid of the disease, what complications and side effects were observed, perhaps not stated by the manufacturer in the annotation. Analogues of Konvulex in the presence of existing structural analogues. Use for the treatment of epilepsy, seizures, convulsions in adults, children, as well as during pregnancy and lactation.

Convulex- antiepileptic drug. It also has a central muscle relaxant and sedative effect.

The mechanism of action is primarily due to an increase in GABA content in the central nervous system 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 is played by the effect of valproic acid on GABAA receptors (activation of GABAergic transmission), as well as the effect on voltage-gated sodium channels. According to another hypothesis, it acts on postsynaptic receptor sites, simulating or enhancing the inhibitory effect of GABA. A possible direct effect on membrane activity is associated with changes in conductivity for potassium ions. Improves the mental state and mood of patients, has antiarrhythmic activity.

Compound

Valproic acid + excipients (capsules, solution for intravenous administration).

Sodium valproate + excipients (tablets, drops, syrup).

Pharmacokinetics

Valproic acid is almost completely absorbed from the gastrointestinal tract, bioavailability when taken orally is 100%. Eating does not reduce the rate of absorption. Concentration values ​​in the cerebrospinal fluid correlate with the value of the non-protein-bound fraction of the active substance. Valproic acid penetrates the placental barrier and is excreted in breast milk. The concentration in breast milk is 1-10% of the concentration in maternal blood plasma. Valproic acid undergoes glucuronidation and oxidation in the liver. Valproic acid (1-3% of the dose) and its metabolites are excreted by the kidneys, small amounts - with feces and exhaled air.

Indications

• epilepsy of various etiologies (idiopathic, cryptogenic and symptomatic);
• generalized epileptic seizures in adults and children (clonic, tonic, tonic-clonic, absence seizures, myoclonic, atonic);
• partial epileptic seizures in adults and children (with or without secondary generalization);
• specific syndromes (West, Lennox-Gastaut);
• behavioral disorders caused by epilepsy;
• febrile convulsions in children, childhood tics;
• treatment and prevention of bipolar affective disorders.

Release forms

Capsules 150 mg, 300 mg and 500 mg.

Extended-release tablets retard 300 mg and 500 mg.

Drops for oral administration.

Syrup for children.

Solution for intravenous administration (injections in injection ampoules).

Instructions for use and dosage

Capsules

Capsules are taken orally, without chewing, 2-3 times a day, during or immediately after meals, with a small amount of water.

Adults are prescribed an initial dose of 600 mg per day with a gradual increase in dose by 150-250 mg every 3 days until a clinical effect is achieved (disappearance of seizures).

The maximum dose is 30 mg/kg per day (in patients with accelerated metabolism of valproic acid, the maximum dose can be increased to 60 mg/kg per day under monitoring of the concentration of valproic acid in the blood plasma).

Retard tablets

Extended-release tablets are taken orally, without chewing, 1-2 times a day, during or immediately after meals, with a small amount of water.

Adults are prescribed an initial dose of 600 mg per day with a gradual increase every 3 days until a clinical effect is achieved (disappearance of seizures).

The initial dose for monotherapy is 5-15 mg/kg per day, then the dose is gradually increased by 5-10 mg/kg per week.

The maximum dose is 30 mg/kg per day (in patients with accelerated metabolism of valproic acid, the maximum dose can be increased to 60 mg/kg per day under monitoring of the concentration of valproic acid in the blood plasma).

When carrying out combination therapy, the dose is 10-30 mg/kg per day, followed by an increase of 5-10 mg/kg per week.

Children weighing more than 25 kg are prescribed an initial dose of 300 mg per day (5-15 mg/kg per day), with a gradual increase by 5-10 mg/kg per week until a clinical effect is achieved (disappearance of seizures), while the dose , as a rule, is 1-1.5 g per day (20-30 mg/kg per day).

The maximum dose is 30 mg/kg per day (in patients with accelerated metabolism of valproic acid, the maximum dose can be increased to 60 mg/kg per day under monitoring of the concentration of valproic acid in the blood plasma).

For children weighing 20-25 kg with monotherapy, the average dose is 15-45 mg/kg per day, the maximum is 50 mg/kg per day. With combination therapy - 30-100 mg/kg per day. It should be taken into account that children weighing less than 20 kg are not recommended to use the drug in the form of extended-release tablets; they should use other forms of the drug.

Although the pharmacokinetics of valproic acid may vary in the elderly, this is of limited clinical significance and dosing should be based on clinical effect. Due to decreased binding to serum albumin, the proportion of unbound drug in plasma increases. This makes it advisable to more carefully select the dose of the drug in the elderly, with the possible use of smaller doses of the drug.

Syrup

Children weighing more than 25 kg are prescribed an initial dose of 300 mg per day with a gradual increase until a clinical effect is achieved (disappearance of seizures), while the dose is usually 20-30 mg/kg per day.

The initial dose for monotherapy is 5-15 mg/kg per day, then the dose is gradually increased by 5-10 mg/kg per week.

The maximum dose is 30 mg/kg per day (can be increased to 60 mg/kg per day under the control of the concentration of valproic acid in the blood plasma).

For children weighing 7.5-25 kg with monotherapy, the average dose is 15-45 mg/kg per day, the maximum is 50 mg/kg per day. With combination therapy - 30-100 mg/kg per day.

Ampoules

The drug is administered intravenously (slowly) or infusion.

When switching from oral administration to intravenous administration, the doses do not change; the first intravenous administration is recommended 12 hours after the last oral administration. The injection solution 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 dosage regimen is recommended: intravenous administration at a dose of 15 mg/kg over 5 minutes, after 30 minutes begin infusion at a rate of 1 mg/kg/h with constant monitoring of concentration until a level of plasma about 75 μg/ml.

The maximum daily dose of the drug should not exceed 2500 mg.

Average daily doses are 20 mg/kg in adults (including elderly patients), 25 mg/kg in adolescents, 30 mg/kg in children.

Isotonic sodium chloride solution, 5% glucose solution, and Ringer's solution can be used as an infusion solution for Convulex. The prepared solution for infusion can be used within 24 hours; the unused volume of the solution is destroyed. If other drugs are also used intravenously, Convulex should be administered via a separate infusion system.

Side effect

• nausea, vomiting;
• gastralgia;
• decreased or increased appetite;
• diarrhea, constipation;
• pancreatitis;
• tremor;
• diplopia;
• nystagmus;
• flashing "flies" before the eyes;
• behavior changes;
• mood or mental state (depression, feeling tired, hallucinations, aggressiveness, hyperactivity, psychosis, unusual agitation, restlessness or irritability);
• ataxia;
• dizziness;
• drowsiness;
• headache;
• encephalopathy;
• dysarthria;
• enuresis;
• stupor;
• disturbance of consciousness;
• coma;
• anemia, leukopenia, thrombocytopenia;
• decrease in fibrinogen content and platelet aggregation, leading to the development of hypocoagulation (accompanied by prolongation of bleeding time, petechial hemorrhages, bruises, hematomas, bleeding);
• decrease or increase in body weight;
• dysmenorrhea;
• secondary amenorrhea;
• enlargement of the mammary glands;
• galactorrhea;
• hyperbilirubinemia;
• skin rash;
• hives;
• angioedema;
• photosensitivity;
• malignant exudative erythema (Stevens-Johnson syndrome);
• peripheral edema;
• hair loss (usually recovers after discontinuation of the drug).

Contraindications

• liver failure;
• acute and chronic hepatitis;
• pancreatic dysfunction;
• porphyria;
• hemorrhagic diathesis;
• severe thrombocytopenia;
• disorders of urea metabolism (including family history);
• combination with mefloquine, St. John's wort, lamotrigine;
• 1st trimester of pregnancy (for syrup);
• lactation period;
• children under 3 years of age (for capsules, tablets);
• hypersensitivity to valproic acid and its salts or components of the drug.

Use during pregnancy and breastfeeding

During treatment with Convulex, you should protect against pregnancy.

In the 1st trimester of pregnancy you should not start treatment with Convulex. If a pregnant woman is already receiving the drug, treatment should not be interrupted due to the risk of increased seizures. The drug should be used in the minimum effective dose, avoiding combination with other anticonvulsants and, if possible, regularly monitoring drug plasma levels.

Experimental studies on animals revealed the teratogenic effect of valproic acid.

The incidence of neural tube defects in children born to women who took valproate in the 1st trimester of pregnancy is 1-2%. In this regard, it is advisable to use folic acid preparations.

During lactation, the use of the drug Konvulex is contraindicated. At the same time, breastfeeding is possible, because the concentration in breast milk does not exceed 1-10% of the drug level in the mother’s blood plasma.

Use in children

Contraindicated in children under 3 years of age (for extended-release tablets and capsules).

special instructions

Due to reports of severe and fatal cases of liver failure and pancreatitis when using valproic acid preparations, the following should be kept in mind:

• at increased risk are infants and children under 3 years of age with severe epilepsy, often associated with brain damage and congenital metabolic or degenerative diseases;
• in most cases, liver dysfunction 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 patient's age;
• insufficiency of liver function with pancreatitis increases the risk of death;
• early diagnosis (before the icteric stage) is based mainly on clinical observation - identification of early symptoms such as asthenia, anorexia, extreme fatigue, drowsiness, sometimes accompanied by vomiting and abdominal pain; in this case, a relapse of epileptic seizures may occur against the background of unchanged antiepileptic therapy.

In such cases, you should immediately consult a doctor for a clinical examination and liver function test.

During treatment, especially in the first 6 months, it is necessary to periodically check liver function - liver transaminase activity, levels of prothrombin, fibrinogen, coagulation factors, bilirubin concentration, as well as amylase activity (every 3 months, especially when combined with other antiepileptic drugs) and picture of peripheral blood, in particular blood platelets.

In patients receiving other antiepileptic drugs, transfer to valproic acid should be carried out gradually, reaching a clinically effective dose after 2 weeks, after which gradual withdrawal of other antiepileptic drugs is possible. In patients not treated with other antiepileptic drugs, a clinically effective dose should be achieved after 1 week.

The risk of side effects from the liver is increased during combination anticonvulsant therapy, as well as in children. Drinks containing ethanol (alcohol) are not allowed.

Before surgery, a general blood test (including platelet count), determination of bleeding time, and coagulogram parameters are required.

If the symptom complex “acute abdomen” occurs during treatment, it is recommended to determine the activity of amylase in the blood before the start of surgery to exclude acute pancreatitis.

During treatment, one should take into account the possible distortion of the results of urine tests in diabetes mellitus (due to an increase in the content of ketone bodies) and indicators of thyroid function.

If any acute serious side effects develop, you should immediately discuss with your doctor the advisability of continuing or stopping treatment.

To reduce the risk of developing dyspeptic disorders, it is possible to take antispasmodics and enveloping agents.

Abruptly stopping taking Convulex may lead to an increase in epileptic seizures.

Impact on the ability to drive vehicles and operate machinery

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug interactions

Contraindicated combinations

Mefloquine. Risk of epileptic seizures due to increased metabolism of valproic acid and a decrease in its plasma concentration and, on the other hand, the convulsant effect of mefloquine.

St. John's wort. The risk of a decrease in the concentration of valproic acid in the blood plasma.

Lamotrigine. Increased risk of severe skin reactions (toxic epidermal necrolysis). Valproic acid inhibits microsomal liver enzymes that ensure the metabolism of lamotrigine, which slows down its T1/2 to 70 hours in adults and up to 45-55 hours in children and increases plasma concentrations. If the combination is necessary, careful clinical and laboratory monitoring is required.

Combinations requiring special precautions

Carbamazepine. Convulex increases the concentration of the active metabolite of carbamazepine in plasma to the point of signs of overdose. In addition, carbamazepine enhances the hepatic metabolism of valproic acid and reduces its concentration. These circumstances require the attention of a doctor and determination of drug concentrations in plasma and a possible revision of their doses.

Phenobarbital, primidone. Valproic acid increases plasma concentrations of phenobarbital or primidone to the point of signs of overdose, more often in children. In turn, phenobarbital or primidone enhance the hepatic metabolism of valproic acid and reduce its concentration. Clinical observation is recommended during the first 2 weeks of combination treatment with an immediate reduction in the dose of phenobarbital or primidone if signs of sedation appear, and determination of the level of anticonvulsants in the blood.

Phenytoin. Changes in the concentration of phenytoin in plasma are possible; phenytoin increases the hepatic metabolism of valproic acid and reduces its concentration. Clinical observation is recommended, determining the level of anticonvulsants in the blood, changing dosages if necessary.

Clonazepam. The addition of valproic acid to clonazepam in isolated cases can lead to increased severity of absence status.

Ethosuximide. Convulex can either increase or decrease the concentration of ethosuximide in the blood serum due to changes in its metabolism. Clinical observation is recommended, determining the level of anticonvulsants in the blood, changing dosages if necessary.

Topiramate. The risk of developing hyperammonemia and encephalopathy increases.

Felbamate. An increase in the concentration of valproic acid in plasma by 35-50%, with the risk of overdose. Clinical observation, determination of the level of valproic acid in the blood, and changes in the dosage of valproic acid when combined with felbamate and after its discontinuation are recommended.

Neuroleptics, MAO inhibitors, antidepressants, benzodiazepines. Neuroleptics, tricyclic antidepressants, MAO inhibitors, which reduce the threshold for convulsive readiness, reduce the effectiveness of the drug. In turn, valproic acid potentiates the effect of these psychotropic drugs, as well as benzodiazepines.

Cimetidine, erythromycin. Suppress the hepatic metabolism of valproic acid and increase its concentration in plasma.

Zidovudine. Valproic acid increases the plasma concentration of zidovudine, which leads to increased toxicity.

Carbapenems, monobactams. Meropenem, panipenem, as well as aztreonam and imipenem reduce the plasma concentration of valproic acid, which may lead to a decrease in the anticonvulsant effect.

Combinations to consider

Acetylsalicylic acid. Strengthening the effects of valproic acid due to its displacement from plasma proteins. Valproic acid enhances the effect of acetylsalicylic acid.

Indirect anticoagulants. Valproic acid enhances the effect of indirect anticoagulants; careful monitoring of the prothrombin index is necessary when administered together with vitamin K-dependent anticoagulants.

Nimodipine. Strengthening the hypotensive effect of nimodipine due to an increase in its concentration in plasma due to the suppression of its metabolism by valproic acid.

Myelotoxic drugs. Increased risk of suppression of bone marrow hematopoiesis.

Ethanol (alcohol) and hepatotoxic drugs. Increase the likelihood of developing liver damage.

Other combinations

Oral contraceptives. Valproic acid does not induce liver microsomal enzymes and does not reduce the effectiveness of hormonal oral contraceptives.

Analogues of the drug Konvulex

Structural analogues of the active substance:

• Valparine;
• Sodium valproate;
• Valproic acid Sandoz;
• Depakine;
• Depakine chrono;
• Depakin Chronosphere;
• Depakine enteric;
• Dipromal;
• Convulsofin;
• Encorat;
• Encorat chrono.

If there are no analogues of the drug for the active substance, you can follow the links below to the diseases for which the corresponding drug helps, and look at the available analogues for the therapeutic effect.

Instructions for use
Convulex

Dosage forms

Tablets 300mg
tablets 500mg

Synonyms
Valparin XP
Depakin
Depakin Chrono
Depakin Chronosphere
Depakine enteric 300
Convulsofin
Enkorat

Group
Anticonvulsants - valproate

International nonproprietary name
Valproic acid

Compound
Active ingredient: Valproic acid.

Manufacturers
Gerot Pharmaceuticals GmbH (Austria)

pharmachologic effect
Antiepileptic, muscle relaxant, sedative. By inhibiting GABA transferase, it increases the content of gamma-aminobutyric acid in the central nervous system, which causes a decrease in the threshold of excitability and the level of convulsive readiness of the motor areas of the brain. When taken orally, it dissociates to valproate ion, which is absorbed into the blood plasma. Food reduces the rate of absorption. Metabolized in the liver. Metabolites and conjugates are excreted by the kidneys. A small amount of valproic acid is excreted in milk.

Side effect
Nausea, vomiting, diarrhea, stomach pain, anorexia or increased appetite, impaired liver function, drowsiness, tremor, paresthesia, confusion, peripheral edema, bleeding, leukopenia, thrombocytopenia. With long-term use - temporary hair loss.

Indications for use
Various forms of generalized seizures: small (absences), large (convulsive) and polymorphic; used for focal seizures, childhood tics.

Contraindications
Hypersensitivity, incl. “familial” (death of close relatives while taking valproic acid), diseases of the liver and pancreas (in some patients there may be a significant decrease in metabolism in the liver), hemorrhagic diathesis, pregnancy (first trimester), breastfeeding. Restrictions on use. Children's age (simultaneous administration of several anticonvulsants), bone marrow aplasia, pregnancy (late stages).

Directions for use and dosage

Orally, during or after meals, without chewing, with a small amount of liquid. Adults: initial daily dose - 15 mg/kg. The frequency of administration is 2-3 times a day. The dose is gradually increased by 5-10 mg/kg per week until a clinical effect is achieved. The average daily dose is about 1000-2000 mg/day, i.e. 20-30 mg/kg body weight. If necessary, the dose can be increased to 2500 mg/day. The maximum dose is 30 mg/kg/day (can be increased if it is possible to monitor plasma concentrations up to 60 mg/kg/day). With combination therapy - 10-30 mg/kg/day, followed by increasing the dose by 5-10 mg/kg/week. Children: average daily dose for body weight 7.5-14 kg - 150-450 mg/day, 14-21 kg - 300-600 mg/day, 21-32 kg - 600-900 mg/day, 32-50 kg - 900-1500 mg/day.
Overdose
No data.

Interaction
The effect is enhanced by other anticonvulsants, sedatives and hypnotics. Dyspeptic disorders develop less frequently against the background of antispasmodics and enveloping agents. Alcohol and other hepatotoxic drugs increase the likelihood of liver damage, anticoagulants or acetylsalicylic acid - the risk of bleeding.

special instructions
No data.

Storage conditions
Sp. B. In a dry place, protected from light, at a temperature of 15-21°C.

Instructions for use

Active ingredients

Release form

Compound

Sodium valproate 300 mgExcipients: sodium saccharinate - 8.5 mg, orange flavor - 2 mg, hydrochloric acid 37% - q.s. to pH 9.0, sodium hydroxide - q.s. to pH 9.0, purified water - up to 1 ml.

Pharmacological effect

Antiepileptic drug. It also has a central muscle relaxant and sedative effect. The mechanism of action is primarily due to an increase in the content of GABA in the central nervous system 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 is played by the effect of valproic acid on GABAA receptors (activation of GABA-ergic transmission), as well as the effect on voltage-dependent sodium channels. According to another hypothesis, it acts on postsynaptic receptor sites, simulating or enhancing the inhibitory effect of GABA. A possible direct effect on membrane activity is associated with changes in conductivity for potassium ions. Improves the mental state and mood of patients, has antiarrhythmic activity.

Pharmacokinetics

Absorption Valproic acid is almost completely absorbed from the gastrointestinal tract, bioavailability when taken orally is 100%. Eating does not reduce the rate of absorption. Cmax in blood plasma after taking extended-release tablets is achieved after 4 hours, Cmax in blood plasma after taking oral drops - after 1-3 hours. The therapeutic concentration of valproic acid in blood plasma is 50-150 mg/l. The prolonged form is characterized by a slow absorption, lower (25%), but more stable plasma concentration between 4 and 14 hours. Distribution of Css is achieved on days 2-4 of treatment, depending on the intervals between doses. At plasma concentrations up to 50 mg/l, binding valproic acid with plasma proteins is 90-95%, at a concentration of 50-100 mg/l - 80-85%. The concentration values ​​in the cerebrospinal fluid correlate with the value of the non-protein-bound fraction of the active substance. Valproic acid penetrates 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 Valproic acid undergoes 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. T1/2 of valproic acid in monotherapy and in healthy volunteers is 8-20 hours. Pharmacokinetics in special clinical cases With uremia, hypoproteinemia and cirrhosis, the binding of valproic acid to plasma proteins decreases. When combined with other drugs, T1/2 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 T1/2 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 (Westa, Lennox-Gastaut); behavioral disorders caused by epilepsy; febrile convulsions in children, childhood tics; treatment and prevention of bipolar affective disorders (for oral drops); treatment and prevention of bipolar affective disorders resistant to treatment with lithium drugs or other medications (for extended-release tablets).

Contraindications

Liver failure; acute and chronic hepatitis; pancreatic dysfunction; porphyria; hemorrhagic diathesis; severe thrombocytopenia; urea metabolism disorders (including family history); combination with mefloquine, St. John's wort, lamotrigine; lactation period; children with weight body weight less than 7.5 kg (for oral drops); children weighing less than 20 kg (for extended-release tablets); children under 3 years of age (for extended-release tablets); hypersensitivity to valproic acid and its salts or components drug. With caution: with anamnestic data on diseases of the liver and pancreas (including family history); with suppression of bone marrow hematopoiesis (leukopenia, thrombocytopenia, anemia); with renal failure; with congenital enzymopathies; with organic diseases of the brain ;for hypoproteinemia; during pregnancy (especially the first trimester); for children with mental retardation; for children weighing more than 7.5 kg (for oral drops).

Precautionary measures

Use for liver dysfunction Contraindicated in severe liver dysfunction. The drug should be prescribed with extreme caution if there is a history of liver disease. Use for impaired renal function Patients with renal failure may need to reduce the dose of the drug. The dose is set by monitoring the patient’s clinical condition, because values ​​for the concentration of valproic acid in blood plasma may not be sufficiently informative. Use in children Contraindication: children under 3 years of age (for tablets with prolonged action).

Use during pregnancy and breastfeeding

During treatment, pregnancy should be protected. Experiments on animals revealed the teratogenic effect of valproic acid. The incidence of neural tube defects in children born to women who took valproate in the first trimester of pregnancy is 1-2%. In this regard, it is advisable to use folic acid preparations. In the first trimester of pregnancy, treatment with Convulex should not be started. If a pregnant woman is already receiving the drug, treatment should not be interrupted due to the risk of increased seizures. The drug should be used in the lowest effective doses, avoiding combination with other anticonvulsants and, if possible, regularly monitoring the concentration of valproic acid in plasma.

Directions for use and doses

Drops for oral administration are taken orally 2-3 times a day, regardless of meals, with a small amount of water. Adults are prescribed an initial dose of 600 mg/day with a gradual increase every 3 days until a clinical effect is achieved (disappearance of seizures). monotherapy is 5-15 mg/kg/day, then the dose is gradually increased by 5-10 mg/kg per week. The recommended daily dose is about 1-2 g, i.e. 20-30 mg/kg. If necessary, the dose can 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 monitoring the concentration of valproic acid in the blood plasma). When carrying out combination therapy, the dose is 10-30 mg/kg/day, followed by an increase of 5-10 mg/kg per week. Children weighing more than 25 kg are prescribed an initial dose of 300 mg/kg day (5-15 mg/kg/day), with a gradual increase by 5-10 mg/kg per week until a clinical effect is achieved (disappearance of seizures), while the dose is usually 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 the blood plasma). For children with body weight 7.5-25 kg with monotherapy, the average dose is 15-45 mg/kg/day, the maximum is 50 mg/kg/day. With combination therapy - 30-100 mg/kg/day. It should be taken into account that children weighing less than 20 kg are not recommended to use the drug in the form of extended-release tablets; they should use other forms of the drug.

Side effects

In general, Konvulex is well tolerated by patients. Side effects are possible mainly when the concentration of the drug in plasma is above 100 mg/l or with combination therapy. From the digestive system: nausea, vomiting, gastralgia, decreased or increased appetite, diarrhea, hepatitis, constipation, pancreatitis, up to severe lesions with lethal outcome (in the first 6 months of treatment, more often at 2-12 weeks). From the central nervous system: tremor, diplopia, nystagmus, floaters flashing before the eyes, changes in behavior, mood or mental state (depression, feeling tired, hallucinations, aggressiveness, hyperactive condition, psychosis, unusual agitation, motor restlessness or irritability), ataxia, dizziness, drowsiness, headache, encephalopathy, dysarthria, enuresis, stupor, impaired consciousness, coma. From the hematopoietic system: anemia, leukopenia, thrombocytopenia, decreased fibrinogen and platelet aggregation, leading to the development of hypocoagulation (accompanied by prolongation of bleeding time, petechial hemorrhages, bruises, hematomas, bleeding). From the metabolic side: decrease or increase in body weight. From the endocrine system: dysmenorrhea, secondary amenorrhea, enlarged mammary glands, galactorrhea. From laboratory parameters: hypercreatininemia, hyperammonemia, hyperbilirubinemia, slight increase in the activity of liver transaminases, LDH (dose-dependent). Allergic reactions: skin rash, urticaria, angioedema, photosensitivity, malignant exudative erythema (Stevens-Johnson syndrome). Others: peripheral edema, hair loss (usually recovers after discontinuation of the drug).

Overdose

Symptoms: nausea, vomiting, dizziness, diarrhea, respiratory dysfunction, muscle hypotonia, hyporeflexia, miosis, coma. Treatment: gastric lavage (no later than 10-12 hours) followed by the administration of activated charcoal, hemodialysis. Forced diuresis, maintaining vital body functions.

Interaction with other drugs

Contraindicated combinations Mefloquine: risk of epileptic seizures due to increased metabolism of valproic acid and a decrease in its concentration in plasma and, on the other hand, the convulsant effect of mefloquine. St. John's wort: risk of decreased concentration of valproic acid in blood plasma. Not recommended combinations Lamotrigine: increased risk of severe skin reactions (toxic epidermal necrolysis). Valproic acid inhibits microsomal liver enzymes that ensure the metabolism of lamotrigine, which slows down its T1/2 to 70 hours in adults and up to 45-55 hours in children and increases plasma concentrations. If the combination is necessary, careful clinical and laboratory monitoring is required. Combinations requiring special precautions Carbamazepine: Valproic acid increases the plasma concentration of the active metabolite of carbamazepine to the point of signs of overdose. In addition, carbamazepine enhances the hepatic metabolism of valproic acid and reduces its concentration. These circumstances require the attention of a doctor and determination of drug concentrations in plasma and possible revision of their doses. Phenobarbital, primidone: valproic acid increases the concentration of phenobarbital or primidone in plasma to signs of overdose, more often in children. In turn, phenobarbital or primidone enhance the hepatic metabolism of valproic acid and reduce its concentration. Clinical observation is recommended during the first 2 weeks of combination treatment with an immediate reduction in the dose of phenobarbital or primidone if signs of sedation appear, determining the level of anticonvulsants in the blood. Phenytoin: changes in the concentration of phenytoin in plasma are possible, phenytoin increases the hepatic metabolism of valproic acid and reduces its concentration. Clinical observation is recommended, determining the level of anticonvulsants in the blood, changing dosages if necessary. Clonazepam: the addition of valproic acid to clonazepam in isolated cases can lead to an increase in the severity of absence status. Ethosuximide: valproic acid can either increase or decrease the concentration of ethosuximide in the blood serum due to changes in its metabolism. Clinical observation is recommended, determining the level of anticonvulsants in the blood, changing dosages if necessary. Topiramate: increases the risk of hyperammonemia and encephalopathy. Felbamate: increases the concentration of valproic acid in plasma by 35-50%, with the risk of overdose. Clinical observation, determination of the level of valproic acid in the blood, and changes in the dosage of valproic acid when combined with felbamate and after its discontinuation are recommended. Neuroleptics, MAO inhibitors, antidepressants, benzodiazepines: neuroleptics, tricyclic antidepressants, MAO inhibitors, which lower the seizure threshold, reduce the effectiveness of the drug. In turn, valproic acid potentiates the effect of these psychotropic drugs, as well as benzodiazepines. Cimetidine, erythromycin: suppress the hepatic metabolism of valproic acid and increase its concentration in plasma. Zidovudine: valproic acid increases the concentration of zidovudine in plasma, which leads to increased toxicity. Carbapenems , monobactams: meropenem, panipenem, as well as aztreonam and imipenem reduce the concentration of valproic acid in plasma, which can lead to a decrease in the anticonvulsant effect. Combinations that should be taken into account Acetylsalicylic acid: increased effects of valproic acid due to its displacement from plasma proteins. Valproic acid enhances the effect of acetylsalicylic acid. Indirect anticoagulants: valproic acid enhances the effect of indirect anticoagulants; careful monitoring of the prothrombin index is necessary when co-administered with vitamin K-dependent anticoagulants. Nimodipine: increased hypotensive effect of nimodipine due to an increase in its concentration in plasma due to suppression of its metabolism valproic acid. Myelotoxic drugs: increased risk of suppression of bone marrow hematopoiesis. Ethanol and hepatotoxic drugs: increase the likelihood of developing liver damage. Other combinations Oral contraceptives: valproic acid does not induce microsomal liver enzymes and does not reduce the effectiveness of hormonal oral contraceptives.

special instructions

Due to reports of severe and fatal cases of liver failure and pancreatitis with the use of valproic acid drugs, the following should be kept in mind: - infants and children under 3 years of age are at increased risk, with severe epilepsy, often associated with brain damage and congenital metabolic disorders. or degenerative diseases; - in most cases, liver dysfunction 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; - insufficiency of liver function in pancreatitis increases the risk of death; - early diagnosis (before the icteric stage) is based mainly on clinical observation - identification of early symptoms such as asthenia, anorexia, extreme fatigue, drowsiness, sometimes accompanied by vomiting and pain in the stomach; in this case, a recurrence of epileptic seizures may occur against the background of unchanged antiepileptic therapy. In such cases, you should immediately consult a doctor for a clinical examination and analysis of liver function. During treatment, especially in the first 6 months, it is necessary to periodically check liver function - the activity of liver transaminases, the level of prothrombin, fibrinogen, coagulation factors, bilirubin concentration, as well as amylase activity (every 3 months, especially when combined with other antiepileptic drugs) and the picture of peripheral blood, in particular, blood platelets. Patients who receive other antiepileptic drugs, transfer to the appointment Valproic acid should be administered gradually, reaching a clinically effective dose after 2 weeks, after which gradual withdrawal of other antiepileptic drugs is possible. In patients who have not received treatment with other antiepileptic drugs, a clinically effective dose should be achieved after 1 week. The risk of side effects from the liver is increased during combination anticonvulsant therapy, as well as in children. Drinks containing ethanol are not allowed. Before surgery, a general blood test (including platelet count), determination of bleeding time, and coagulogram parameters are required. If symptoms of an acute abdomen occur during treatment, it is recommended to determine amylase activity in the blood before surgery. to exclude acute pancreatitis. During treatment, possible distortion of the results of urine tests in diabetes mellitus (due to an increase in the content of ketone bodies), indicators of thyroid function should be taken into account. If any acute serious side effects develop, you should immediately discuss with your doctor the advisability of continuing or stopping treatment. To reduce the risk of developing dyspeptic symptoms it is possible to take antispasmodics and enveloping agents. Abrupt cessation of taking Konvulex can lead to an increase in epileptic seizures. Impact on the ability to drive vehicles and operate machinery During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed psychomotor reactions.

KNF (medicine included in the Kazakhstan National Formulary of Medicines)

ALO (Included in the List of free outpatient drug provision)

ED (Included in the List of drugs within the framework of the guaranteed volume of free medical care, subject to purchase from the Single Distributor)

Manufacturer: G.L.Pharma GmbH

Anatomical-therapeutic-chemical classification: Valproic acid

Registration number: No. RK-LS-5 No. 014717

Registration date: 31.10.2014 - 31.10.2019

Limit price: 26.4 KZT

Instructions

• Russian

Tradename

Convulex®

International nonproprietary name

Valproic acid

Dosage form

Extended release film-coated tablets, 300 mg and 500 mg

Compound

One tablet contains

active substance - sodium valproate 300 or 500 mg,

Excipients: citric acid monohydrate, ethylcellulose 100 cps, ammonium methacrylate copolymer, type B (Eudrazhit RS30D), purified talc, anhydrous colloidal silicon dioxide, magnesium stearate

shell composition: ammonium methacrylate copolymer, type A (Eudragit RL30D), ammonium methacrylate copolymer, type B (Eudragit RS30D), triethyl citrate, sodium carmellose, titanium dioxide (E171), purified talc, vanillin.

Description

Tablets are oval-shaped, film-coated, white, with a line on one side of the line engraved “SS” on the other “3”, with the smell of vanillin, length from 14.8 to 15.4 mm, width from 7.8 to 8.3 mm and height from 5.3 to 5.8 mm (for a dosage of 300 mg).

Tablets, oval, film-coated, white, with a line on one side of the line engraved “SS” on the other “5”, with the smell of vanillin, length from 17.2 to 17.8 mm, width from 8.8 to 9.3 mm and height from 6.5 to 7.1 mm (for a dosage of 500 mg).

Farmacotherapy group

Antiepileptic drugs. Fatty acid derivatives. Valproic acid.

ATX code N03AG01

Pharmacological properties

Pharmacokinetics

Valproic acid is quickly and almost completely absorbed from the gastrointestinal tract, bioavailability when taken orally is 100%. Eating does not reduce the rate of absorption. The maximum level of concentration in plasma is observed after 1-6 hours. Equilibrium concentration is achieved on days 2-4 of treatment, depending on the dosing intervals. The therapeutic concentration of the drug in blood plasma ranges from 40-100 mg/l. Valproic acid is bound 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; with uremia, hypoproteinemia and cirrhosis, protein binding is reduced. The level of concentration in the cerebrospinal fluid correlates with the size of the non-protein-bound fraction of the drug. Valproic acid penetrates the placental barrier and is excreted in breast milk. The concentration in breast milk is 1-10% of the concentration in maternal blood plasma. 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 feces and exhaled air. The half-life of the drug in monotherapy is from 10 to 15 hours, in children 6-10 hours, when combined with other drugs the half-life can be 6-8 hours due to the induction of metabolic enzymes, in patients with impaired liver function and elderly patients it can be significantly longer.

The prolonged form is characterized by the absence of absorption latency, slow absorption, lower (25%), but relatively more stable plasma concentrations between 4 and 14 hours.

Pharmacodynamics

Konvulex is an antiepileptic drug that also has a central muscle relaxant and sedative effect. The mechanism of action is primarily due to inhibition of the GABA transferase enzyme and an increase in GABA content in the central nervous system. GABA inhibits pre- and postsynaptic discharges and thereby prevents the spread of seizure activity into the central nervous system. In addition, in the mechanism of action of the drug, a significant role is played by the effect of valproic acid on GABA A receptors, as well as the effect on voltage-dependent Na channels. Acts on sites of postsynaptic receptors, simulating or enhancing the inhibitory effect of GABA. A possible direct effect on membrane activity is associated with changes in potassium conductance. Improves the mental state and mood of patients, has antiarrhythmic activity.

Indications for use

Epileptic seizures (including generalized and partial, as well as against the background of organic brain diseases)

Manic-depressive syndrome with bipolar course, when lithium is contraindicated or not tolerated by the patient

Directions for use and doses

The drug is taken orally, without chewing, 1 time per day, during or after meals, with a small amount of liquid. The duration of use is determined by the doctor.

Adults

The initial dose for monotherapy is 5-10 mg/kg/day, for combination therapy - 10-30 mg/kg/day, then this dose is gradually increased by 5-10 mg/kg/week.

The average daily dose is 20-30 mg/kg body weight.

The daily dose can be increased to 60 mg/kg if it is possible to monitor the concentration of the drug in the blood plasma.

Children

For use in children under 6 years of age, the following forms of the drug Convulex are recommended: drops for oral administration and syrup for children.

The dosage for children 6 years of age and older is 10-20 mg/kg with a gradual increase to 20-30 mg/kg per day. In children requiring doses greater than 40 mg/kg per day, biochemical and hematological parameters should be monitored.

Elderly age

Although the pharmacokinetics of valproate in the elderly varies, it is of limited clinical significance and dosage should be based on clinical effect. Due to decreased binding to serum albumin, the proportion of unbound drug in plasma increases. This makes it advisable to more carefully select the dose of the drug in the elderly, with the possible use of smaller doses of the drug.

Patients with renal failure

It may be necessary to reduce the dose of the drug. The dose should be selected based on monitoring of the clinical condition, since plasma concentrations may not be sufficiently informative.

Average daily doses:

Side effects

Side effects are possible mainly when the drug level in plasma is above 100 mg/l or during combination therapy.

Often (from 1/100 to<1/10 случаев)

- nausea, vomiting, anorexia or increased appetite, diarrhea, gastralgia, hepatitis

- tremor

- diplopia, flashing spots before the eyes

- anemia, thrombocytopenia, decreased fibrinogen content, platelet aggregation and blood clotting, accompanied by prolongation of bleeding time, petechial hemorrhages, bruising, hematomas, bleeding, agranulocytosis, lymphocytosis

- weight loss or gain

- hypercreatininemia, hyperammonemia, hyperglycinemia, hyperbilirubinemia, slight increase in the activity of “liver” transaminases, LDH (dose-dependent)

- dysmenorrhea, secondary amenorrhea, breast enlargement, galactorrhea

- peripheral edema, hair loss (usually recovers after discontinuation of the drug)

Vasculitis

Hearing impairment, paresthesia

Polycystic ovary syndrome

Enuresis in children

Rarely (from 1/10,000 to<1/1,000 случаев)

Changes in behavior, mood or mental status (depression, feeling tired, hallucinations, aggressiveness, hyperactivity, psychosis, unusual agitation, restlessness or irritability), ataxia, dizziness, somnolence, headache, encephalopathy, dysarthria, stupor, altered consciousness, coma

- leukopenia, pancytopenia, lymphocytosis, erythrocyte hypoplasia

Liver dysfunction

Systemic lupus erythematosus

Lethargy, confusion

Headache, nystagmus

- skin rash, urticaria, angioedema, photosensitivity

Very rarely (<1/10,000 случаев)

Encephalopathy, coma

Pancreatitis, up to severe lesions with a fatal outcome (in the first 6 months of treatment, more often at 2-12 weeks)

Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme

Reversible Fanconi syndrome

Bone marrow aplasia

Hyponatremia

Renal dysfunction

Contraindications

hypersensitivity to valproate or any of the excipients

severe dysfunction of the liver and/or pancreas

hepatic porphyria

acute and chronic hepatitis

a case of severe hepatitis in the patient’s personal or family history, including those associated with taking medications

thrombocytopenia

hemorrhagic diathesis

combination with carbapenems

combination with St. John's wort

combination with mefloquine

children up to 6 years old

pregnancy and lactation

children under 18 years of age with manic-depressive syndrome with bipolar course

Drug interactions

When valproic acid is used concomitantly with drugs that depress the central nervous system (tricyclic antidepressants, monoamine oxidase inhibitors (MAO) inhibitors and antipsychotics), increased central nervous system depression may occur. Ethanol and other hepatotoxic drugs increase the likelihood of developing liver damage. Tricyclic antidepressants, MAO inhibitors, antipsychotics and other drugs that lower the threshold for seizure activity reduce the effectiveness of valproic acid.

Convulex, depending on its concentration in plasma, can displace thyroid hormones from their binding sites to plasma protein and cause their metabolism, which can lead to a false diagnosis indicating hypothyroidism.

Other antiepileptic drugs with an enzyme-inducing effect (phenytoin, phenobarbital, primidone, carbamazepine) reduce the concentration of valproate in the blood plasma. When carrying out combination therapy, the dosage should be adjusted according to the level of the drug in the blood.

The simultaneous use of antidepressants, neuroleptics, tranquilizers, barbiturates, MAO inhibitors, thymoleptics, ethanol with Konvulex is not recommended. The addition of valproate to clonazepam in isolated cases can lead to increased severity of absence status.

Valproate may decrease the metabolism of lamotrigine and increase its mean half-life. Dose adjustment may be required (lower dose of lamotrigine). Concomitant use of lamotrigine and valproate may increase the risk of (severe) skin reactions, especially in children).

Valproate may increase the plasma concentration of zidovudine, which will lead to increased toxicity of the latter.

With the simultaneous use of valproic acid with barbiturates or primidone, an increase in their concentration in the blood plasma is observed. Increases the half-life (T1/2) of lamotrigine (inhibits liver enzymes, causes a slowdown in the metabolism of lamotrigine, as a result of which its T1/2 is extended to 45-55 hours - in children). Reduces the clearance of zidovudine by 38%, while its T1/2 does not change.

When combined with salicylates, an increase in the effects of valproic acid is observed (displacement from plasma proteins). Konvulex 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 plasma by 35-50% (dose adjustment is necessary).

With the combined use of cimetidine or erythromycin. The concentration of valproate in the blood plasma may increase (due to a decrease in its metabolism in the liver).

Cholestyramine may reduce the absorption of valproic acid.

When taken concomitantly with Rifampicin, the risk of seizures increases due to increased hepatic metabolism of valproate under the influence of rifampicin. Clinical and laboratory monitoring is recommended, and dose adjustment of the anticonvulsant drug is possible during treatment with rifampicin and after its discontinuation.

Valproic acid does not induce liver enzymes and does not reduce the effectiveness of oral contraceptives.

special instructions

Particular caution is required when prescribing Convulex to the following categories of patients:

With anamnestic data on diseases of the liver and pancreas, as well as bone marrow damage

With impaired renal function

With congenital enzymopathies

Mentally retarded children

For hypoproteinemia

During treatment with the drug, alcohol consumption is not allowed. Suicidal thinking and behavior was observed among patients receiving antiepileptic agents for some indications. The mechanism by which this risk occurs remains unknown, and available data do not exclude the possibility of an increased risk due to the use of valproic acid.

Therefore, patients should be closely monitored for signs of suicidal ideation and behavior, and initiation of appropriate treatment should be considered. Patients (and caregivers) should be advised to seek immediate medical attention if suicidal ideation or behavior occurs.

For liver disorders

Before starting treatment and periodically during the first six months of treatment, especially among patients at risk and those with a history of liver disease, liver function parameters should be continuously monitored. Such patients should be under close medical supervision.

Liver function tests include prothrombin time, aminoferase and/or bilirubin levels, and/or fibrinogen breakdown products. At the first stage, there may be an increase in aminoferase levels; this is usually a temporary phenomenon that responds to dose reduction.

Patients with abnormal biochemical tests should undergo repeat clinical evaluation and liver function (including prothrombin time) should be monitored until normal. However, an excessively prolonged prothrombin time, especially if it is associated with abnormal values ​​of other relevant tests, requires discontinuation of treatment.

Hepatic dysfunction, including liver failure leading to death, has been reported in patients treated with valproic acid or sodium valproate. Patients most often at risk are children, especially those younger than 3 years of age, and patients with inherited metabolic or degenerative disorders, organic brain dysfunction, or severe seizures associated with mental retardation. Most of these events occurred during the first six months of therapy, predominantly at weeks 2 to 12, and typically included multidrug anticonvulsant therapy. For this group of patients, monotherapy is preferred.

In the early stages of liver failure, clinical symptoms can be more helpful in correcting the diagnosis than laboratory tests. Severe or fatal liver disease may be preceded by unusual symptoms, usually of sudden onset, such as loss of seizure control, discomfort, weakness, lethargy, edema, loss of appetite, vomiting, abdominal pain, drowsiness and jaundice. They represent indications for immediate discontinuation of the drug. Patients should be instructed to immediately report any such signs to their healthcare provider for appropriate evaluation. Although it is difficult to establish which tests can provide accurate predictions, tests that measure protein synthesis, such as prothrombin time, are thought to still be the most relevant.

In patients with hepatic dysfunction, concomitant use of the salicylic acid salt should be discontinued as it may share the same metabolic pathway and thereby increase the risk of hepatic failure.

For hematological disorders

Before surgery, a general blood test (including platelet count), determination of bleeding time, and coagulogram parameters are required. Patients with a history of bone marrow involvement should also be closely monitored.

For pancreatic disorders

In very rare cases, severe pancreatitis has been reported, which could be fatal. The risk of death is most common in young children and decreases with increasing age. Severe seizures or neurological disorders during combination anticonvulsant therapy may be risk factors for serious pancreatitis. If kidney failure occurs along with pancreatitis, the risk of death increases. Patients should be advised that they should contact their physician immediately if they develop symptoms suggestive of pancreatitis (eg, abdominal pain, nausea, vomiting). Such patients should undergo a thorough medical evaluation (including measurement of serum amylase levels); If pancreatitis is diagnosed, sodium valproate should be discontinued. Patients with a history of pancreatitis should be under close clinical supervision.

For diabetes

During treatment, one should take into account the possible distortion of the results of urine tests in diabetes mellitus (due to an increase in the content of keto products) and indicators of thyroid function.

Weight gain

Valproate very often causes weight gain, which can be noticeable and progressive. Patients should be advised of this risk at the start of treatment, as well as appropriate measures to minimize weight gain.

Hyperammonemia

If an enzymatic deficiency of the urea cycle is suspected, metabolic studies should be carried out before starting treatment, as there is a risk of hyperammonemia with valproate.

If any acute serious side effects develop, you should immediately discuss with your doctor the advisability of continuing or stopping treatment.

To reduce the risk of developing dyspeptic disorders, it is possible to take antispasmodics and enveloping agents.

Abruptly stopping taking Convulex may lead to an increase in epileptic seizures.

The risk of malformations caused by valproate is 3 to 4 times higher in pregnant women taking this drug than the risk found in the general population, which is 3%. The most commonly observed malformations are neural tube closure defects (approximately 2-3%), facial dysmorphia, facial clefts, craniostenosis, cardiac defects, renal and urinary tract malformations, and limb deformities.

Doses exceeding 1000 mg/day and combination with other anticonvulsants are important risk factors for the formation of malformations in the fetus.

Current epidemiological data do not indicate a decrease in the overall IQ of children with exposure to sodium valproate.

However, some decrease in verbal abilities and/or more frequent use of speech therapists or additional classes have been described in such children. In addition, several cases of autism and related disorders have been reported in children exposed to sodium valproate in utero. Additional studies are needed to confirm or refute these results.

When planning a pregnancy

If pregnancy is planned, you should definitely decide on the use of other medications.

If the use of sodium valproate is unavoidable (i.e. there is no other alternative), it is recommended to prescribe the minimum effective daily dose. Sustained-release dosage forms should be used or, if this is not possible, the daily dose should be divided into several doses. This is necessary in order to avoid peaks in the maximum concentrations of valproic acid in the blood plasma.

Given the beneficial effects of folic acid before pregnancy, additional folic acid supplementation at a dose of 5 mg/day can be suggested 1 month before conception and for 2 months after it. Screening for birth defects should be the same for everyone, regardless of whether the pregnant woman is taking folic acid or not.

During pregnancy

If choosing another drug is absolutely impossible and treatment with sodium valproate must be continued, it is recommended to prescribe the minimum effective dose. Doses exceeding 1000 mg/day should be avoided whenever possible. Regardless of folic acid intake, screening for fetal abnormalities is necessary for all pregnant women.

Before delivery, a coagulation test should be performed, including platelet count, fibrinogen level and clotting time (activated partial thromboplastin time, aPTT).

Newborns

Convulex can cause the development of hemorrhagic syndrome in newborns, not associated with vitamin K deficiency.

Normal indicators of maternal hemostasis do not exclude the possibility of pathology in the newborn. Therefore, the newborn's platelet count, fibrinogen level, and activated partial thromboplastin time (aPTT) should be determined. Hypoglycemia has also been reported in newborns in the first week of life.

Lactation

Valproate is excreted in breast milk in small amounts (1-10% of the drug level in the mother's blood plasma). However, due to data on reduced verbal abilities in young children, patients should be advised not to breastfeed.

Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

Overdose

Symptoms: nausea, vomiting, dizziness, diarrhea, respiratory dysfunction, muscle hypotonia, hyporeflexia, miosis, coma.

Treatment: gastric lavage (no later than 10-12 hours), activated charcoal, IV naloxone, hemodialysis, hemoperfusion, forced diuresis, maintenance of respiration and cardiovascular functions

Release form and packaging

50 tablets are placed in amber-colored hydrolytic class III bottles, sealed with a white tamper-evident screw cap made of high-density polyethylene. Or 50 tablets in a polyethylene bottle with a lid and first opening control.

1 bottle, along with instructions for medical use in the state and Russian languages, is placed in a cardboard pack.

Storage conditions

Store at a temperature not exceeding 25°C, in a dry place, protected from light.

Keep out of the reach of children!

Shelf life

Do not use the drug after the expiration date.

Conditions for dispensing from pharmacies

On prescription

Manufacturer

"G.L. Pharma GmbH., Industriestrasse 1, A-8502 Lannach, Austria

Registration Certificate Holder

LLC "Valeant", Russia

Address of the organization that receives claims (suggestions) from consumers regarding product quality in the territory of the Republic of Kazakhstan and is responsible for post-registration surveillance and safety of the medicinal product

Valeant LLP

Kazakhstan, 050059, Almaty, Al-Farabi Avenue,

17, Block 4B, office 1104

Phone + 7 727 3 111 516, fax +7 727 3 111 517

Email: [email protected]

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