Cough

Convulex liquid for oral administration. Konvulex syrup - official instructions for use

Dosage form"type="checkbox">

Dosage form

Syrup for children

Compound

100 ml syrup contains

active substance - sodium valproate 5.00 g (obtained from valproic acid 4.338 g and sodium hydroxide 1.204 g),

excipients: liquid maltitol, methyl 4-hydroxybenzoate, propyl 4-hydroxybenzoate, sodium saccharin, sodium cyclamate, sodium chloride, raspberry flavor (9/372710), peach flavor additive (9/030307), purified water.

Description

The syrup is colorless to slightly yellowish in color, with a peach odor and sweet peach taste.

Pharmacotherapeutic group

Antiepileptic drugs. Fatty acids derivatives. Valproic acid.

ATX code N03AG01

Pharmacological properties"type="checkbox">

Pharmacological properties

Pharmacokinetics

Sodium valproate is rapidly and almost completely absorbed into gastrointestinal tract(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 1-3 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. Concentration levels in cerebrospinal fluid correlate with the size of the non-protein-bound fraction of the drug. Valproic acid penetrates the placental barrier and is excreted in breast milk. 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 quantities excreted in feces and exhaled air. The elimination period of the drug is 10-15 hours, in children 6-10 hours, when combined with other medicines 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.

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 enzyme GABA transferase and an increase in the content gamma-aminobutyric acid(GABA) in the central nervous system(CNS). 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 postsynaptic receptor sites, simulating or enhancing the inhibitory effect of GABA. A possible direct effect on membrane activity is associated with changes in potassium conductance. Improves mental state and the mood of patients, has antiarrhythmic activity.

Indications for use

Primary generalized, secondary generalized and partial epileptic seizures

Directions for use and doses

Konvulex syrup should be prescribed and used only under the supervision of a specialist. The dosage, duration of treatment, and discontinuation of the drug are prescribed only by a doctor. The benefits and risks of the drug should be carefully weighed before use. It is preferable to prescribe Convulex as monotherapy, in the minimum effective dose to prevent peak plasma concentrations. Convulex in the form of syrup is specially intended for use in children due to its pleasant taste. The syrup contains a sweetener and does not lead to the formation of caries. The drug is taken orally, 2-3 times a day, during or after meals.

Monotherapy.

In children, the initial dose is 10-20 mg/kg per day with a gradual increase in the dose by 5-10 mg/kg at intervals of 3-7 days, until a dose of 20-30 mg/kg per day is reached. If adequate control is not achieved within this range, the dose may be increased to 35 mg/kg per day. Doses higher than 40 mg/kg/day may be required in in some cases. In children requiring doses greater than 40 mg/kg per day, biochemical and hematological parameters should be monitored.

Children weighing more than 20 kg. Initial daily dose is 300 mg, with a gradual increase in dose until clinical effect(disappearances seizures), which is usually 20-30 mg/kg body weight per day.

Average daily doses:

Combined treatment:

If Convulex syrup is prescribed together with other antiepileptic drugs, then the dosage of the drug that was started earlier should be gradually reduced. The dosage of Convulex syrup should be increased gradually, and the main dosage regimen should be achieved after approximately two weeks of taking the drug. If Convulex syrup is used in combination with anticonvulsants that induce liver enzyme activity, such as phenytoin, phenobarbital or carbamazepine, the dose should be increased from 5 to 10 mg/kg/day.

After a known liver enzyme inducer has been discontinued, it is possible to maintain seizure control on a reduced dose of Convulex syrup. If carried out simultaneous administration with barbiturates, and especially if there is sedative effect(particularly in children), then the dosage of barbiturates should be reduced.

Reducing the dose or stopping the drug is possible no earlier than 2-3 years after the cessation of attacks. Discontinuation of the drug should be carried out gradually over 1-2 years.

Instructions for use of the dosing device.

1. Lower the plunger into the syringe until it stops, then place the syringe in a glass bottle.

2. Raise the piston up until the mark on the piston corresponds to the prescribed dosage (graduation in ml and mg). If necessary, repeat the process until the total prescribed quantity is reached.

3.Using the plunger to press down, apply the measured dose directly into the child's mouth or spoon. Make sure the prescribed dose is received.

4. After each use, close the bottle and rinse the syringe thoroughly with water. Store both the syringe and bottle in a cardboard box.

Side effects"type="checkbox">

Side effects

Convulex is well tolerated by patients. Side effects possible mainly when the drug level in plasma is above 100 mg/l or with combination therapy.

Often (from ³1/100 to<1/10 случаев)

Nausea, vomiting, anorexia or increased appetite, diarrhea, gastralgia, hepatitis

Tremor, paresthesia, ataxia, dizziness

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

Loss or gain of body weight

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)

Hearing impairment, paresthesia

Rarely (from ³1/10,000 to<1/1,000 случаев)

Nausea, vomiting, diarrhea, constipation, increased salivation

Changes in behavior, mood or mental state (depression, feeling tired, hallucinations, aggressiveness, hyperactivity, psychosis, unusual agitation, restlessness or irritability), drowsiness, headache, encephalopathy, dysarthria, stupor, impaired consciousness, ringing in the ears, deterioration hearing

Leukopenia, pancytopenia, lymphocytosis, erythrocyte hypoplasia, agranulocytosis

Liver dysfunction

Systemic lupus erythematosus

Lethargy, confusion

Headache, nystagmus

Skin rash, urticaria, angioedema, photosensitivity

Polycystic ovary syndrome, dysmenorrhea, amenorrhea

Increased appetite

Very rarely (<1/10,000 случаев)

Allergic reactions

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

Parkinson's syndrome

Bone marrow aplasia, decreased fibrinogen levels

Hyponatremia

Renal dysfunction

Gynecomastia, hirsutism

Increase testosterone levels

Porphyria

Frequency unknown

Thrombocytopenia, prolonged bleeding time

Angioedema, vasculitis, drug exanthema with eosinophilia, photosensitivity

Enuresis in children

Hyperammonemia, accompanied by vomiting, ataxia, impaired consciousness

Depression, hyperactivity, behavior changes

Contraindications

Hypersensitivity to valproate or any of the excipients

Severe dysfunction of the liver and/or pancreas

Hepatic porphyria

Acute and chronic hepatitis

Patient's personal or family history of severe hepatitis, including those associated with medication use

Thrombocytopenia

Hemorrhagic diathesis

Combination with carbapenems

Combination with St. John's wort

Combination with mefloquine

Children up to 3 months old

Pregnancy and lactation

Drug interactions

When valproic acid is used concomitantly with drugs that depress the central nervous system (tricyclic antidepressants, monoamine oxidase inhibitors (MAO) inhibitors, benzodiazepines and antipsychotics), increased central nervous system depression may occur. Close medical monitoring and, if necessary, dose adjustment are recommended.

With simultaneous use of Konvulex syrup with diazepam or loracepam, the clearance of the latter in plasma may be reduced.

Ethanol and other hepatotoxic drugs increase the likelihood of developing liver damage. Sodium valproate enhances the effects of alcohol. Tricyclic antidepressants, MAO inhibitors, antipsychotics and other drugs that lower the threshold for seizure activity reduce the effectiveness of valproic acid.

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. Particularly at the beginning of combination treatment, careful medical monitoring and dosage adjustment are recommended.

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. Prothrombin time should be monitored during anticoagulant therapy.

When combined with phenobarbital, phenytoin, carbamazepine, mefloquine, the content of valproic acid in the blood serum decreases (acceleration of metabolism).

Encephalopathy and/or hyperammonemia have been reported with concomitant use of valproate and topiromate. These patients should be closely monitored.

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.

Fluoxetine can affect the concentration of valproic acid, both increasing and decreasing.

Special instructions

Because of its high teratogenic potential and risk of development of disorders in children exposed to valproate in utero, Convulex should be used in girls, adolescent girls, women of childbearing potential, and pregnant women when alternative treatments are ineffective or intolerant. When prescribing the drug during puberty, in women of childbearing age, when planning pregnancy and during pregnancy, the benefits and risks must be carefully weighed. Patients of childbearing potential should use effective contraception during treatment and should be advised of the risks associated with the use of Convulex during pregnancy.

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

With organic brain damage

For hypoproteinemia

During treatment with the drug, alcohol consumption is not allowed. Suicidal ideation and behavior have been reported 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 repeated clinical evaluation, and liver functions (including prothrombin time) should be monitored until they return to 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 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. Convulex 50 mg/ml syrup for children contains artificial sweeteners and therefore can be used by patients with diabetes. However, the carbohydrate content of 0.05 BU (dietary units) per ml of syrup should be taken into account.

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 there is a suspicion of enzymatic deficiency of the urea cycle, metabolic studies should be carried out before starting treatment, as there is a risk of hyperammonemia with the use of 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 can lead to an increase in epileptic seizures.

Thyroid hormones: Depending on their plasma concentrations, valproate may displace thyroid hormones from plasma proteins and increase their metabolism, which may lead to a misdiagnosis of hypothyroidism.

In patients with known or suspected mitochondrial disease, Convulex may induce or enhance clinical signs of underlying mitochondrial disease caused by mutations in mitochondrial DNA or the nuclear POLG gene.

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

By prescription

Manufacturer

"G.L. Pharma GmbH., Austria, A-1160, Vienna, Arnetgasse 3

Before using CONVULEX you should consult your doctor. These instructions for use are for informational purposes only. For more complete information, please refer to the manufacturer's instructions.

Clinical and pharmacological group

02.011 (Anticonvulsant)

Release form, composition and packaging

Enteric-soluble soft gelatin capsules, pink, enteric-coated, marked “150” in gray ink; the contents of the capsules are a colorless or colorless liquid with a slightly yellowish tint, with a weak characteristic odor.

Excipients:

Capsule body composition: carion 83 (mannitol 2-4%, sorbitol 27-32%, hydrogenated starch 61-71%) - 15.14 mg, glycerol 85% - 21.63 mg, gelatin - 71.56 mg, titanium dioxide - 0.67 mg, iron oxide red (E172) - 0.17 mg, hydrochloric acid 25% - 0.57 mg.

Composition of the enteric coating: 30% dispersion of copolymer of methacrylic acid and ethyl acrylate (1:1) dry (sodium lauryl sulfate 0.7%, polysorbate-80 2.3%) - 17.55 mg, triethyl citrate - 2.81 mg, macrogol 6000 - 0.88 mg, glyceryl monostearate 45-55 type II - 0.53 mg.

Composition of capsule marking ink: shellac - 47.5%, titanium dioxide, black iron oxide dye, butanol, water, propylene glycol, denatured ethanol (methylated alcohol), isopropanol.

Enteric-soluble soft gelatin capsules, pink, enteric-coated, marked “300” in gray ink; the contents of the capsules are a colorless or colorless liquid with a slightly yellowish tint, with a weak characteristic odor.

Excipients:

Capsule body composition: carion 83 (mannitol 2-4%, sorbitol 27-32%, hydrogenated starch 61-71%) - 24.94 mg, glycerol 85% - 35.63 mg, gelatin - 117.86 mg, titanium dioxide - 1.1 mg, iron oxide red (E172) - 0.28 mg, hydrochloric acid 25% - 0.94 mg.

Composition of the enteric coating: 30% dispersion of copolymer of methacrylic acid and ethyl acrylate (1:1) dry (sodium lauryl sulfate 0.7%, polysorbate-80 2.3%) - 28.83 mg, triethyl citrate - 4.61 mg, macrogol 6000 - 1.44 mg, glyceryl monostearate 45-55 type II - 0.86 mg.

20 pcs. - blisters (5) - cardboard packs.

Enteric-soluble soft gelatin capsules, pink, enteric-coated, marked “500” in gray ink; the contents of the capsules are a colorless or colorless liquid with a slightly yellowish tint, with a weak characteristic odor.

Excipients:

Capsule body composition: carion 83 (mannitol 2-4%, sorbitol 27-32%, hydrogenated starch 61-71%) - 40.97 mg, glycerol 85% - 58.53 mg, gelatin - 193.64 mg, titanium dioxide - 1.81 mg, iron oxide red (E172) - 0.46 mg, hydrochloric acid 25% - 1.54 mg.

Composition of the enteric coating: 30% dispersion of copolymer of methacrylic acid and ethyl acrylate (1:1) dry (sodium lauryl sulfate 0.7%, polysorbate-80 2.3%) - 47.62 mg, triethyl citrate - 7.62 mg, macrogol 6000 - 2.38 mg, glyceryl monostearate 45-55 type II - 1.43 mg.

Composition of capsule marking ink: shellac 47.5%, titanium dioxide, black iron oxide dye, butanol, water, propylene glycol, denatured ethanol (methylated alcohol), isopropanol.

10 pcs. - blisters (10) - cardboard packs.

Pharmacological action

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 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

Suction

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 plasma is observed after 2-3 hours. The therapeutic concentration of valproic acid in blood plasma is 50-150 mg/l.

Distribution

Css is achieved on days 2-4 of treatment, depending on the intervals between doses.

At a concentration in blood plasma of up to 50 mg/l, the binding of valproic acid to plasma proteins is 90-95%, at a concentration of 50-100 mg/l - 80-85%.

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 plasma.

Metabolism

Valproic acid undergoes glucuronidation and oxidation in the liver.

Removal

Valproic acid (1-3% of the dose) and its metabolites are excreted by the kidneys, small amounts - with feces and exhaled air. T1/2 with monotherapy and in healthy volunteers is 8-20 hours.

Pharmacokinetics in special clinical situations

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 18 months of age, a significant increase in T1/2 is possible.

CONVULEX: DOSAGE

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/day with a gradual increase in dose by 150-250 mg every 3 days until a clinical effect is achieved (disappearance of seizures).

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

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/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 , 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 monitoring 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/day, the maximum is 50 mg/kg/day. With combination therapy - 30-100 mg/kg/day.

Average daily doses of Convulex

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.

In 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.

Patient's body weight (kg)
Dose (mg/day)
Quantity of capsules 150 mg
Number of capsules 300 mg
Number of capsules 500 mg
7.5-14
150-450
1-3
–
–
14-21
300-600
2-4
1-2
–
21-32
600-900
4-6
2-3
–
32-50
900-1500
–
3-5
2-3
50-90
1500-2500
–
–
3-5

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, maintenance of function.

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: risk of reducing 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 provide metabolism, which slows down its T1/2 to 70 hours in adults and up to 45-55 hours in children and increases the concentration in the blood plasma. 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 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 when 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.

: 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 serum concentrations of ethosuximide 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: increased plasma concentrations of valproic acid by 35-50%, with risk of overdose. Clinical observation and level determination are recommended when combined with felbamate and after its discontinuation.

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 plasma concentration.

Zidovudine: Valproic acid increases the plasma concentration of zidovudine, leading to increased toxicity.

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

Combinations to consider

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 administered together with vitamin K-dependent anticoagulants.

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

Myelotoxic drugs: increased risk of bone marrow hematopoiesis suppression.

Ethanol 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.

Pregnancy and lactation

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.

CONVULEX: SIDE EFFECTS

In general, Konvulex® 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.

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

From the side of the central nervous system: tremor, diplopia, nystagmus, flickering of “floaters” before the eyes, changes in behavior, mood or mental state (depression, fatigue, hallucinations, aggressiveness, hyperactive state, psychosis, unusual agitation, restlessness or irritability), ataxia, dizziness, drowsiness, headache, encephalopathy, dysarthria, enuresis, stupor, impaired consciousness, coma.

From the hematopoietic system: 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).

From the metabolic side: decrease or increase in body weight.

From the endocrine system: dysmenorrhea, secondary amenorrhea, breast enlargement, galactorrhea.

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).

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

Storage conditions and periods

The drug should be stored out of the reach of children at a temperature not exceeding 30°C. Shelf life - 5 years.

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 (Vesta,
Lennox-Gastaut);
behavioral disorders,
caused by epilepsy;
febrile seizures in children,
baby tic;
treatment and prevention of bipolar affective disorders.

Contraindications

liver failure;
acute and chronic hepatitis;
pancreatic dysfunction;
porphyria;
hemorrhagic diathesis;
severe thrombocytopenia;
disorders of urea metabolism (incl.
in family history);
combination with mefloquine,
St. John's wort,
lamotrigine;
lactation period;
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 diseases of the liver and pancreas (incl.
in family history);
with suppression of bone marrow hematopoiesis (leukopenia,
thrombocytopenia,
anemia);
with renal failure;
for congenital enzymopathies;
for organic diseases of the brain;
with hypoproteinemia;
during pregnancy (especially the first trimester);
children with mental retardation.

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:

the high-risk group includes 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 patient age;
insufficiency of liver function with pancreatitis increases the risk of death;
early diagnosis (before the icteric stage) is based mainly on clinical observation - identifying 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.

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 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 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 of psychomotor reactions.

Use for renal impairment

Patients with renal failure may require a dose reduction. The dose is set by monitoring the patient’s clinical condition, because values of valproic acid concentration in blood plasma may not be sufficiently informative.

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.

Antiepileptic drug.
Drug: CONVULEX®

Active substance of the drug: valproic acid
ATX encoding: N03AG01
KFG: Anticonvulsant drug
Registration number: P No. 011170/02
Registration date: 07.29.05
Owner reg. credential: GEROT PHARMAZEUTIKA GmbH (Austria)

Konvulex release form, drug packaging and composition.

Pink soft gelatin capsules, enteric coated; The capsule is printed in black ink “150”.

1 caps.
valproic acid
150 mg

Pink soft gelatin capsules, enteric coated; The capsule is printed in black ink “300”.

1 caps.
valproic acid
300 mg

Excipients: sorbitol (Karion 83), glycerol 85%, gelatin, titanium dioxide, red iron oxide (E172), hydrochloric acid 25%, shellac, black iron oxide (E172), hypromellose phthalate, dibutyl phthalate.

20 pcs. - blisters (5) - cardboard packs.

Pink soft gelatin capsules, enteric coated; “500” is printed on the capsule in black ink.

1 caps.
valproic acid
500 mg

Excipients: sorbitol (Karion 83), glycerol 85%, gelatin, titanium dioxide, red iron oxide (E172), hydrochloric acid 25%, shellac, black iron oxide (E172), hypromellose phthalate, dibutyl phthalate.

10 pcs. - blisters (10) - cardboard packs.

Extended-release tablets, white, oval, biconvex, vanilla-flavored, with a score line and “CC3” engraved on one side; on a cross section - white.

1 tab.
sodium valproate
300 mg

Extended-release tablets, white, oval, biconvex, vanilla-flavored, with a score line and engraved “CC5” on one side; on a cross section - white.

1 tab.
sodium valproate
500 mg

Excipients: citric acid monohydrate, ethylcellulose, Eudragit RS30D, purified talc, colloidal anhydrous silicon, magnesium stearate, Eudragit L30D, dibutyl phthalate, sodium carmellose, macrogol 6000, titanium dioxide, vanillin, simethicone.

50 pcs. — polyethylene bottles (1) — cardboard packs.
50 pcs. - glass bottles (1) - cardboard packs.

Drops for oral administration in the form of a colorless or slightly yellowish solution.

1 ml
sodium valproate
300 mg

Excipients: purified water.

100 ml - glass bottles (1) - cardboard packs.

Syrup for children is colorless or slightly yellowish, with a peach aroma and a sweet peach taste.

1 ml
sodium valproate
50 mg

Excipients: sodium hydroxide, lycasin 80/55, sodium saccharin, sodium cyclamate, methylhydroxybenzoate, propylhydroxybenzoate, sodium chloride, raspberry (9/372710) and peach (9/030307) flavorings, purified water.

100 ml - dark glass bottles (1) complete with a dosing glass - cardboard packs.

The description of the drug is based on the officially approved instructions for use.

Pharmacological action of Konvulex

Antiepileptic drug. The mechanism of action is due to inhibition of the GABA transferase enzyme and an increase in the content of GABA in the central nervous system. GABA 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 GABAA receptors, as well as the effect on voltage-dependent Na channels. Another hypothesis is that valproic acid acts at postsynaptic receptor sites, mimicking or enhancing the inhibitory effect of GABA. A possible direct effect on membrane activity is associated with changes in potassium permeability.

Improves the mental state and mood of patients, has antiarrhythmic activity.

Pharmacokinetics of the drug.

Suction

Valproic acid is quickly and almost completely absorbed from the gastrointestinal tract, bioavailability when taken orally is about 100%. Eating does not reduce the rate of absorption. Cmax in plasma is observed after 3-4 hours. The therapeutic concentration of valproic acid in blood plasma is 50-100 mg/l.

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

Distribution

Css is achieved on days 2-4 of treatment, depending on the intervals between doses.

At a concentration in blood plasma of up to 50 mg/l, the binding of valproic acid to plasma proteins is 90-95%, at a concentration of 50-100 mg/l - 80-85%.

Metabolism

Valproic acid is metabolized in the liver by oxidation and conjugation with glucuronic acid.

Removal

Valproic acid (1-3% of the dose) and its metabolites are excreted by the kidneys, in small quantities - with feces and exhaled air. T1/2 with monotherapy and in healthy volunteers is 8-20 hours.

Pharmacokinetics of the drug.

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 and the elderly, a significant increase in T1/2 is possible.

In elderly patients, due to decreased binding of the active substance to serum albumin, an increase in the plasma level of unbound drug is possible.

Indications for use:

Epilepsy of any origin;

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

Behavioral disorders associated with epilepsy;

Febrile seizures in children;

Manic-depressive syndrome with a bipolar course that cannot be treated with lithium or other medications.

Dosage and method of administration of the drug.

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).

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

The average 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.

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/day with a gradual increase until a clinical effect is achieved (disappearance of seizures), while the dose is usually 20-30 mg/kg/day.

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

The maximum dose is 30 mg/kg/day (can be increased to 60 mg/kg/day under monitoring 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/day, the maximum is 50 mg/kg/day. With combination therapy - 30-100 mg/kg/day.

In children weighing from 7.5 to 17 kg, it is preferable to use the drug in the form of capsules (150 mg or 300 mg), drops, or syrup.

The average doses of Convulex in capsule form are presented in Table 1.

Table 1
Patient's body weight (kg)
Dose (mg/day)
Quantity of capsules 150 mg
Number of capsules 300 mg
Number of capsules 500 mg
7.5-14
150-450
1-3
—
—
14-21
300-600
2-4
1-2
—
21-32
600-900
4-6
2-3
—
32-50
900-1500
—
3-5
2-3
50-90
1500-2500
—
—
3-5

The average doses of Convulex in the form of drops and syrup are presented in Table 2.

Table 2
Patient's body weight (kg)
Dose (mg/day)
Quantity of syrup (ml)
Number of drops
7.5-14
150-450
3-9
15-45
14-21
300-600
6-12
30-60
21-32
600-900
12-18
60-90
32-50
900-1500
—
—
50-90
1500-2500
—
—

In elderly patients, the dose should be determined more carefully, taking into account the clinical effect; It may be necessary to use the drug in smaller doses.

The daily dose of the drug in the form of capsules, drops for oral administration and syrup is distributed into 2-3 doses; The daily dose of the drug in the form of tablets with prolonged action is distributed into 1-2 doses. The drug is taken regardless of meals.

Extended-release capsules and tablets are taken without chewing with a small amount of liquid. Drops and syrup are taken with a small amount of liquid.

Side effects of Convulex:

The development of side effects is possible mainly when the concentration of the drug in the blood plasma is more than 100 mg/kg or during combination therapy.

From the digestive system: possible nausea, vomiting, gastralgia, anorexia 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).

From the side of the central nervous system: possible tremor, diplopia, nystagmus, flashing “spots” before the eyes; rarely - changes in behavior, mood or mental state (depression, feeling tired, hallucinations, aggressiveness, hyperactive state, psychosis, unusual agitation, restlessness or irritability), ataxia, dizziness, drowsiness, headache, dysarthria, stupor, impaired consciousness, coma .

From the hematopoietic system: possible anemia, leukopenia, thrombocytopenia, decreased fibrinogen content, platelet aggregation and blood clotting, accompanied by an increase in bleeding time, petechial hemorrhages, bruises, hematomas, bleeding.

From the side of metabolism: a decrease or increase in body weight is possible.

From the endocrine system: possible dysmenorrhea, secondary amenorrhea, enlarged mammary glands, galactorrhea.

Laboratory parameters: hypercreatininemia, hyperammonemia, hyperbilirubinemia, slight increase in the activity of liver transaminases, LDH (dose-dependent).

Allergic reactions: possible skin rash, urticaria, angioedema, photosensitivity, Stevens-Johnson syndrome.

Other: swelling, hair loss (usually recovers after discontinuation of the drug).

Side effects are possible mainly when the level of valproic acid in the blood plasma is above 100 mg/l or with combination therapy.

Contraindications to the drug:

Severe liver dysfunction;

Severe pancreatic dysfunction;

Porphyria;

Hemorrhagic diathesis;

Severe thrombocytopenia;

I trimester of pregnancy;

Lactation (breastfeeding);

Children under 3 years of age (for tablets with prolonged action);

Hypersensitivity to valproic acid.

The drug should be prescribed with extreme caution if there is a history of liver and pancreas diseases or bone marrow lesions; with impaired renal function; patients with congenital enzymopathies; mentally retarded children; with organic brain lesions; with hypoproteinemia.

Use during pregnancy and lactation.

Konvulex is contraindicated for use in the first trimester of pregnancy.

If pregnancy occurs, treatment should not be interrupted due to the risk of worsening the condition. Convulex should be used in the lowest effective doses, avoid combination with other anticonvulsants, and regularly monitor plasma valproic acid levels.

If it is necessary to use Convulex during lactation, the issue of stopping breastfeeding should be decided.

Women of childbearing age should use reliable methods of contraception during treatment.

Experimental studies have established the teratogenic effect of the drug.

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, during pregnancy it is advisable to use folic acid supplements.

Special instructions for the use of Convulex.

For patients receiving other antiepileptic drugs, transfer to Konvulex 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 year of therapy.

When conducting combined anticonvulsant therapy, the risk of side effects from the liver increases.

In patients receiving Convulex, 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 level of amylase in the blood before surgery to exclude acute pancreatitis.

It should be taken into account that during treatment, the results of urine tests for diabetes mellitus (due to an increase in the content of keto products) and indicators of thyroid function may be distorted.

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

The patient should be warned to consult with a physician about the advisability of continuing or discontinuing treatment if any acute serious side effects develop.

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

During the period of use of the drug, you should avoid drinking alcohol.

Control of laboratory parameters

Before starting therapy and during the period of use of the drug, it is necessary to regularly monitor liver function (liver transaminase activity, bilirubin content), peripheral blood picture, state of the blood coagulation system, amylase activity (every 3 months, especially when combined with other antiepileptic drugs).

Use in pediatrics

When using the drug in children, the risk of developing side effects from the liver increases.

Impact on the ability to drive vehicles and operate machinery

Patients taking Convulex should refrain from engaging in potentially hazardous activities that require increased attention and speed of psychomotor reactions.

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 respiratory and cardiovascular function.

Interaction of Konvulex with other drugs.

Pharmacodynamic interaction

With simultaneous use of valproic acid with drugs that have a depressant effect on the central nervous system (including tricyclic antidepressants, MAO inhibitors and antipsychotics), as well as with ethanol, increased central nervous system depression may occur.

Hepatotoxic drugs (including ethanol) increase the likelihood of developing liver damage.

Drugs that lower the seizure threshold (including tricyclic antidepressants, MAO inhibitors, antipsychotics) reduce the effectiveness of valproic acid.

Konvulex enhances the effects (including side effects) of other anticonvulsants (phenytoin, lamotrigine), antidepressants, antipsychotics, tranquilizers, barbiturates, MAO inhibitors, thymoleptics, ethanol. When using valproate in patients receiving clonazepam, in isolated cases an increase in the severity of absence status was observed.

Pharmacokinetic interaction

With the simultaneous use of valproic acid with barbiturates or with primidone, an increase in their concentrations in the blood plasma is observed. Due to inhibition of liver enzymes under the influence of valproic acid and a slowdown in the metabolism of lamotrigine, its T1/2 increases to 70 hours in adults and to 45-55 hours in children.

Valproic acid reduces the clearance of zidovudine by 38%, while its T1/2 does not change.

When used simultaneously with salicylates, an increase in the effects of valproic acid is observed due to its displacement from plasma proteins. Konvulex enhances the effects of antiplatelet agents (acetylsalicylic acid) and indirect anticoagulants.

When combined with phenobarbital, phenytoin, carbamazepine, mefloquine, the content of valproic acid in the blood serum decreases (acceleration of metabolism).

Felbamate increases the concentration of valproic acid in the blood plasma by 35-50% (dose adjustment is necessary).

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

Terms of sale in pharmacies.

The drug is available with a prescription.

Terms of storage conditions for the drug Convulex.

List B. Capsules, drops for oral administration, syrup should be stored in a dry place, protected from light, at a temperature of 15° to 25°C. Shelf life: 5 years.

Extended-release tablets should be stored at temperatures below 25°C. Shelf life: 3 years.

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, colloidal anhydrous 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 score on one side of the score, 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).

Pharmacotherapeutic 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 plasma concentration 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 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 postsynaptic receptor sites, 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.

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.

Old age

Although the pharmacokinetics of valproate in the elderly varies, it 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.

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 ³1/100 to<1/10 случаев)

Nausea, vomiting, anorexia or increased appetite, diarrhea, gastralgia, hepatitis

Diplopia, flashing spots before the eyes

Loss or gain of body weight

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 ³1/10,000 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

Patient's personal or family history of severe hepatitis, including those associated with medication use

Thrombocytopenia

Hemorrhagic diathesis

Combination with carbapenems

Combination with St. John's wort

Combination with mefloquine

Children under 6 years old

Pregnancy and lactation

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

Drug interactions

With simultaneous use of valproic acid with drugs that depress the central nervous system (tricyclic antidepressants, monoamine oxidase inhibitors (MAO) 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.

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

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.

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

For liver disorders

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 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

For pancreatic disorders

For diabetes

Weight gain

Hyperammonemia

If there is a suspicion of enzymatic deficiency of the urea cycle, metabolic studies should be carried out before starting treatment, as there is a risk of hyperammonemia with the use of 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 can lead to an increase in epileptic seizures.

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.

When planning a pregnancy

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

During pregnancy

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.

Lactation

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.

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

By prescription

Manufacturer

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

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

Trade name

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

Farmacotherapy group

Antiepileptic drugs. Fatty acid derivatives. Valproic acid.

ATX code N03AG01

Pharmacological properties

Pharmacokinetics

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

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.

Old age

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)

- 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

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

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.

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.

For liver disorders

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

For pancreatic disorders

For diabetes

Weight gain

Hyperammonemia

If there is a suspicion of enzymatic deficiency of the urea cycle, metabolic studies should be carried out before starting treatment, as there is a risk of hyperammonemia with the use of 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 can lead to an increase in epileptic seizures.

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.

When planning a pregnancy

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

During pregnancy

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.

Lactation

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 system 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

By 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

E-mail: [email protected]