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Konvuleks release form. Konvuleks: instructions for use of syrup, drops, solution, tablets and capsules

Catad_pgroup Antiepileptic

Convulex for injections - instructions for use

INSTRUCTIONS
on the medical use of the drug

Registration number:

Trade name of the drug:

Convulex ®

International non-proprietary name (INN):

valproic acid

Dosage form:

Solution for intravenous administration.

Compound:

5 ml of solution (1 ampoule) contains: active substance - sodium valproate 500.0 mg (equivalent to valproic acid 433.9 mg); excipients: sodium hydroxide 117.0 mg, sodium hydrogen phosphate dodecahydrate 71.8 mg, water for injection up to 5.0 ml.

Description. Clear colorless or almost colorless liquid.

Pharmacotherapeutic group:

Antiepileptic drug.

ATX code: N03AG01

pharmachologic effect

KONVULEKS ® is an antiepileptic drug that also has a central muscle relaxant and sedative effect. The mechanism of action is due mainly 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 belongs to the effect of valproic acid on GABA A receptors (activation of GABAergic transmission), as well as to the effect on voltage-gated sodium channels. According to another hypothesis, it acts on the sites of postsynaptic receptors, imitating or enhancing the inhibitory effect of GABA. A possible direct effect on membrane activity is associated with changes in potassium conductivity. Improves the mental state and mood of patients, has antiarrhythmic activity.

Pharmacokinetics
Equilibrium concentration with intravenous administration is reached within a few minutes and can be maintained with a slow infusion. Therapeutic concentration of valproic acid in plasma ranges from 50-150 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, the connection with plasma proteins is reduced.
The concentration in the cerebrospinal fluid correlates with the value of the fraction of valproic acid that is not associated with plasma proteins, amounting to about 10% of the serum value. Valproic acid crosses the placental and blood-brain barriers and is excreted in breast milk. The concentration in breast milk is 1-10% of the concentration in the mother's blood plasma. Valproic acid 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 with feces and exhaled air. The half-life (T1 / 2) of valproic acid is in healthy volunteers and with monotherapy from 8 to 20 hours, when combined with inducers of microsomal liver enzymes involved in the metabolism of valproic acid, T1 / 2 can be 6-8 hours, in patients with impaired liver function, elderly patients and children under 18 months may be significantly longer.

Indications for use

epileptic status.
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 (West, Lennox-Gastaut).
Febrile seizures in children.
Treatment and prevention of bipolar affective disorders.

Contraindications

Hypersensitivity to valproic acid and its salts or drug components
Liver failure
Acute and chronic hepatitis
Pancreatic disorders
porfiria
Hemorrhagic diathesis
Severe thrombocytopenia
Combination with mefloquine, St. John's wort, lamotrigine.
Urea metabolism disorders (including family history)
lactation period

Carefully:

in children in the treatment of several antiepileptic drugs;
in children and adolescents with multiple concomitant diseases and in severe forms of seizures;
with impaired renal function;
in patients with anamnestic data on diseases of the liver and pancreas;
with oppression of bone marrow hematopoiesis; leukopenia, anemia, thrombocytopenia;
with congenital enzymopathies;
with organic brain damage;
with hypoproteinemia;
children's age (up to 3 years);
pregnancy (especially the first trimester)

Application during pregnancy

During treatment should be protected from pregnancy. In animal experiments, the teratogenic effect of valproic acid has been revealed. The incidence of neural tube defects in children born to women 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, you should not start treatment with CONVULEX ® . If the pregnant woman is already receiving the drug, then due to the risk of increased seizures, treatment should not be interrupted. The drug should be used in the smallest effective doses, avoiding combination with other anticonvulsants and, if possible, regularly monitoring the concentration of valproic acid in plasma.

Dosage and administration

KONVULEKS ® solution for injection is used for intravenous (in / in) administration. With intravenous slow administration, the recommended daily dose is 5-10 mg of valproic acid per kg of body weight. With intravenous infusion, the recommended dose is 0.5-1 mg of valproic acid per kg of body weight per hour.
When switching from oral to intravenous administration, the doses do not change, the first intravenous administration is recommended 12 hours after the last oral administration. The introduction of the solution for injection 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 approach is recommended: IV administration of 15 mg/kg over 5 minutes, after 30 minutes, start infusion at a rate of 1 mg/kg/hour with constant monitoring of the concentration until a plasma concentration of about 75 mcg/ml.
The maximum daily dose of the drug should not exceed 2500 mg.
Average daily doses are 20 mg/kg in adults and elderly patients, 25 mg/kg in adolescents, 30 mg/kg in children.
As an infusion solution for Convulex ®, isotonic sodium chloride solution, 5% dextrose solution, Ringer's solution can be used.
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, Konvuleks ® should be administered through a separate infusion system.

Side effects

In general, CONVULEX ® is well tolerated by patients. Side effects are possible mainly at a plasma concentration of valproic acid above 100 mg / l or with combined therapy.
Gastrointestinal tract: nausea, vomiting, gastralgia, decreased or increased appetite, diarrhea, hepatitis, constipation, pancreatitis, up to severe lesions with a fatal outcome (in the first 6 months of treatment, more often for 2-12 weeks).
Central nervous system: 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, impaired consciousness, coma.
From the sense organs: diplopia, nystagmus, flashing "flies" before the eyes.
From the side of the hematopoietic organs and the hemostasis system: anemia, leukopenia; thrombocytopenia, decreased fibrinogen content and platelet aggregation, leading to the development of hypocoagulation (accompanied by prolongation of bleeding time, petechial hemorrhages, bruising, hematomas, bleeding).
From the side of metabolism: decrease or increase in body weight.
Allergic reactions: skin rash, urticaria, angioedema, photosensitivity, malignant exudative erythema (Stevens-Johnson syndrome).
Laboratory indicators: hypercreatininemia, hyperammonemia, hyperbilirubinemia, hyperglycinemia, a slight increase in the activity of "liver" transaminases, lactate dehydrogenase (dose-dependent).
From the endocrine system: dysmenorrhea, secondary amenorrhea, breast enlargement, galactorrhea.
Others: peripheral edema, hair loss (usually recovers after discontinuation of the drug).

Overdose

Symptoms: nausea, vomiting, dizziness, diarrhea, respiratory dysfunction, muscle hypotension, hyporeflexia, miosis, coma. Treatment: hemodialysis, forced diuresis, respiratory and cardiovascular support.

Interaction

Contraindicated combinations:
mefloquine- the risk of epileptic seizures due to increased metabolism of valproic acid and a decrease in its plasma concentration and, on the other hand, the anticonvulsant effect of mefloquine;
Hypericum perforatum- the risk of a decrease in the concentration of valproic acid in the 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 concentration. If a combination is necessary, careful clinical and laboratory monitoring is required.

Combinations requiring special precautions:
carbamazepine- valproic acid increases the concentration of the active metabolite of carbamazepine in plasma to signs of overdose. In addition, carbamazepine enhances the hepatic metabolism of valproic acid and reduces its concentration. These circumstances require the attention of a physician and the determination of plasma drug concentrations and possible revision of their dosages;
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 increase the hepatic metabolism of valproic acid and reduce its concentration. Clinical observation is recommended during the first 2 weeks of combined treatment with an immediate reduction in the dose of phenobarbital or primidone when signs of sedation appear, and determination of the level of antiepileptic drugs in the blood.
phenytoin- possible changes in the concentration of phenytoin in plasma, phenytoin enhances the hepatic metabolism of valproic acid and reduces its concentration. Recommended clinical observation, determination of the level of antiepileptic drugs 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 the absence status;
ethosuximide- valproic acid can both increase and decrease the concentration of ethosuximide in the blood serum due to changes in its metabolism. Recommended clinical observation, determination of the level of antiepileptic drugs 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. Recommended clinical observation, determination of the level of valproic acid in the blood, changing the dosage of valproic acid when combined with felbamate and after its withdrawal;
neuroleptics, monoamine oxidase inhibitors (MAOIs), antidepressants, benzodiazepines- neuroleptics, tricyclic antidepressants, MAO inhibitors, which lower the threshold for convulsive readiness, reduce the effectiveness of the drug. In turn, valproic acid potentiates the action of these psychotropic drugs, as well as benzodiazepines;
cimetidine, erythromycin- inhibit the hepatic metabolism of valproic acid and increase its plasma concentration;
zidovudine- valproic acid increases the plasma concentration of zidovudine, which leads to an increase in its toxicity;
carbapenems, monobactams- meropenem, panipenem, as well as azeonam and imipenem reduce the plasma concentration of valproic acid, which can lead to a decrease in the anticonvulsant effect.

Combinations to consider:
acetylsalicylic acid- enhancing the effects of valproic acid due to its displacement from its association with 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 plasma concentration due to the suppression of its metabolism by valproic acid;
myelotoxic drugs- increased risk of inhibition of bone marrow hematopoiesis;
ethanol and hepatotoxic drugs- increase the risk of liver damage.

Other combinations:
oral contraceptives- valproic acid does not cause the induction of microsomal liver enzymes and does not reduce the effectiveness of hormonal oral contraceptives.

special instructions

In connection with the reports of severe and fatal cases of liver failure and pancreatitis when using valproic acid preparations, the following should be borne in mind:
an increased risk group 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 age of the patient and the 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 hysterical stage) is based mainly on clinical observation - the identification of early symptoms, such as asthenia, anorexia, extreme fatigue, drowsiness, sometimes accompanied by vomiting and abdominal pain; in this case, there may be a relapse of epileptic seizures 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, and amylase activity (every 3 months, especially when combined with other antiepileptic drugs ) and a picture of peripheral blood, in particular, blood platelets.
In patients receiving other antiepileptic drugs, the transition to valproic acid should be carried out gradually, reaching a clinically effective dose after 2 weeks, after which a gradual cancellation of other antiepileptic drugs is possible. In patients who have not received treatment with other antiepileptic drugs, a clinically effective dose should be reached after 1 week.
The risk of developing side effects from the liver is increased during combined anticonvulsant therapy, as well as in children.
Drinks containing ethanol are not allowed.
Before surgery, a general blood test (including platelet counts), determination of bleeding time, and coagulation parameters are required.
If symptoms of an "acute" abdomen occur 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), indicators of thyroid function. With the development of any acute serious side effects, it is necessary to immediately discuss with the 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.
Abrupt discontinuation of CONVULEX ® may lead to an increase in epileptic seizures.
During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions.

Release form

Solution for intravenous administration 100 mg/ml. 5 ml of the drug in a colorless glass ampoule (type I) with a red break point and an orange ring in the upper part; 5 ampoules in a transparent plastic bag; Don; 1 pallet together with instructions for use in a cardboard box.

Storage conditions

At a temperature not exceeding 25 ° C in a place protected from light.
Keep out of the reach of children!

Best before date

5 years.
Do not use after the expiry date stated on the package.

Terms of dispensing from pharmacies

On prescription.

Marketing authorization holder:

LLC "VALEANT", 115162, Moscow, st. Shabolovka, 31, building 5, Russia

Manufacturer of the finished dosage form, packer, labeler:
“G.L. Pharma GmbH, Arnetgasse 3, A-1160 Vienna, Austria

Packer, labeler (optional):
“G.L. Pharma GmbH, Gansterergasse 9-13, 1160 Vienna, Austria

Issuing quality control:
Geroth Pharmaceutics GmbH, Arnetgasse 3, A-1160 Vienna, Austria

Send consumer claims to VALEANT LLC:
115162, Moscow, st. Shabolovka, 31, building 5, Russia

INN: Valproic acid

Manufacturer: G.L.Pharma GmbH

Anatomical-therapeutic-chemical classification: Valproic acid

Registration number in the Republic of Kazakhstan: No. RK-LS-5 No. 014720

Registration period: 02.12.2014 - 02.12.2019

ALO (Included in the Free Outpatient Drug Supply List)

Instruction

Tradename

Convulex®

International non-proprietary name

Valproic acid

Dosage form

Syrup for children

Compound

1 ml syrup contains

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

Excipients: lycasine 80/55 (maltitol solution), methyl 4-hydroxybenzoate, propyl 4-hydroxybenzoate, sodium saccharin, sodium cyclamate, sodium chloride, raspberry flavor (9/372710), peach flavor (9/030307), purified water .

Description

A colorless to slightly yellowish syrup with a peach odor and a sweet peach taste.

Farmacotherapeutic group

Antiepileptic drugs. Fatty acid derivatives. Valproic acid.

ATX code N03AG01

Pharmacological properties

Pharmacokinetics

Sodium valproate is rapidly and almost completely absorbed from the gastrointestinal tract (GIT), oral bioavailability is

100%. Eating does not reduce the rate of absorption. The maximum level of plasma concentration is observed after 1-3 hours. The equilibrium concentration is reached on the 2-4th day 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 concentration levels in the cerebrospinal fluid correlate with the size of the non-protein fraction of the drug. Valproic acid crosses 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. 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 with feces and exhaled air. The elimination period of the drug is 10-15 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 much longer.

Pharmacodynamics

Convulex is an antiepileptic drug, also has a central muscle relaxant and sedative effect. The mechanism of action is due primarily to inhibition of the GABA transferase enzyme and an increase in the content of gamma-aminobutyric acid (GABA) in the central nervous system (CNS). GABA inhibits pre- and postsynaptic discharges and thus prevents the spread of seizure activity in the CNS. In addition, in the mechanism of action of the drug, a significant role belongs to 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, imitating or enhancing the inhibitory effect of GABA. A possible direct effect on membrane activity is associated with changes in potassium conductivity. Improves the mental state and mood of patients, has antiarrhythmic activity.

Indications for use

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

Bipolar manic-depressive disorder when lithium is contraindicated or not tolerated by the patient

Dosage and administration

Convulex syrup is specially designed 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.

In children, the initial dose is 10-20 mg / kg per day with a gradual increase to 20-30 mg / kg per day. In children requiring doses above 40 mg/kg per day, biochemical and haematological parameters should be monitored.

Children weighing over 20 kg. The initial daily dose is 300 mg, with a gradual increase in dose until a clinical effect is achieved (disappearance of convulsive seizures), which is usually 20-30 mg / kg of body weight per day.

Average daily doses:

Instructions for use of the dosing device.

1. Lower the plunger into the syringe down to the stop, then place the syringe in a glass bottle.

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

3. By pushing the plunger down, apply the measured dose directly into the child's mouth, or into a spoon. Make sure you have received the prescribed dose.

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

Side effects

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

Often (from 1/100 to<1/10 случаев)

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

- tremor

- diplopia, flashing "flies" before the eyes

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

- weight loss or gain

- hypercreatininemia, hyperammonemia, hyperglycinemia, hyperbilirubinemia, a 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 loss, paresthesia

Polycystic ovaries

Enuresis in children

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

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, stupor, impaired 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 for 2-12 weeks)

Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme

Reversible Fanconi syndrome

bone marrow aplasia

Hyponatremia

Impaired kidney function

Contraindications

Hypersensitivity to valproate or any of the excipients

Severe disorders 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 that associated with taking medications

Thrombocytopenia

Hemorrhagic diathesis

Combined administration with carbapenems

Combined reception with St. John's wort

Combination with mefloquine

Children's age up to 3 months

Pregnancy and lactation

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

Drug Interactions

With the simultaneous use of valproic acid with drugs that depress the central nervous system (tricyclic antidepressants, monoamine oxidase inhibitors (MAO) and antipsychotics), it is possible to increase depression of the central nervous system. Ethanol and other hepatotoxic drugs increase the likelihood of 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 plasma concentration, can dislodge thyroid hormones from their plasma protein binding sites 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 conducting combination therapy, the dosage should be adjusted in accordance with the level of the drug in the blood.

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

Valproate may decrease the metabolism of lamotrigine and increase its mean half-life. Dose adjustments (lower doses of lamotrigine) may be required. Co-administration of lamotrigine and valproate may increase the risk of (severe) skin reactions, especially in children).

Valproate can increase the concentration of zidovudine in the blood plasma, which will lead to an increase in the toxicity of the latter.

With the simultaneous use of valproic acid with barbiturates or primidone, an increase in their concentration in blood plasma is noted. Increases the half-life (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 45-55 hours in children). Reduces the clearance of zidovudine by 38%, while its T1 / 2 does not change.

When combined with salicylates, there is an increase in the effects of valproic acid (displacement from the connection with plasma proteins). Convulex 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 (metabolism acceleration).

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

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 simultaneously with Rifampicinone, 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 withdrawal.

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

special instructions

Special care is required when prescribing Konvuleks to the following categories of patients:

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

with impaired renal function

with congenital enzymopathies

mentally retarded children

with organic brain damage

with hypoproteinemia

During the period of treatment with the drug, alcohol is not allowed. Suicidal thinking and behavior observed among patients receiving antiepileptic drugs for some indications. The mechanism by which this risk occurs remains unknown, and the 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 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, constant monitoring of liver function parameters should be carried out. Such patients should be under close medical supervision.

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

Patients with abnormal chemistries should be reassessed clinically, and liver function (including prothrombin time) should be monitored until they return to normal. However, an excessively prolonged prothrombin time, especially if associated with abnormal values in other relevant studies, requires discontinuation of treatment.

Liver 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 under 3 years of age, and patients with hereditary 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. Monotherapy is preferred for this group of patients.

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

In patients with hepatic dysfunction, the simultaneous use of salicylic acid salt should be discontinued, as it can use an identical metabolic pathway and, thereby, increase the risk of liver failure.

For hematological disorders

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

For disorders of the pancreas

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

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), indicators of thyroid function.

Weight gain

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

Hyperammonemia

If there is suspicion of enzymatic deficiency of the urea cycle, metabolic studies should be carried out before starting treatment, since there is a risk of hyperammonemia when using valproate.

With the development of any acute serious side effects, it is necessary to immediately discuss with the 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.

Abrupt discontinuation of Convulex may lead to an increase in epileptic seizures.

The risk of malformations caused by valproate is 3-4 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 dysmorphias, facial clefts, craniostenosis, cardiac malformations, kidney and urinary tract malformations, and limb deformities.

Doses greater than 1000 mg/day and combination with other anticonvulsants are important risk factors for fetal malformations.

Current epidemiological data do not indicate a decrease in the general intelligence quotient of children with exposure to sodium valproate.

However, these children have been described to have some reduction in verbal ability and/or more frequent visits to speech therapists or extracurricular activities. In addition, several cases of autism and related disorders have been reported in children exposed to sodium valproate in utero. More research is needed to confirm or refute these results.

When planning a pregnancy

If you plan to become pregnant, 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 peak peak plasma concentrations of valproic acid.

Considering the beneficial effect of folic acid before pregnancy occurs, folic acid supplementation at a dose of 5 mg/day can be suggested 1 month before conception and for 2 months after conception. An examination aimed at identifying malformations should be the same for everyone, regardless of whether the pregnant woman is taking folic acid or not.

During pregnancy

If the choice of another drug is absolutely impossible, and it is necessary to continue treatment with sodium valproate, it is recommended to prescribe the minimum effective dose. Doses in excess of 1000 mg/day should be avoided whenever possible. Regardless of folic acid intake, screening for fetal malformations is essential for all pregnant women.

Before delivery, a coagulogram should be done, in particular, the number of platelets, the level of fibrinogen and the time of blood clotting (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 should have platelet count, fibrinogen levels, and activated partial thromboplastin time (APTT) measured. Newborns have also reported cases of hypoglycemia in the first week of life.

Lactation

Valproate is excreted in breast milk in a small amount (1-10% of the level of the drug in the mother's blood plasma). However, in connection with data on reduced verbal abilities in young children, patients should be advised to stop breastfeeding.

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

Overdose

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

Treatment: gastric lavage (not later than 10-12 hours), activated charcoal, intravenous naloxone, hemodialysis, hemoperfusion, forced diuresis, maintenance of breathing and cardiovascular system functions

Release form and packaging

100 ml of the drug is placed in amber glass bottles with an aluminum cap and control of the first opening. 1 bottle and a polyethylene measuring syringe, together with instructions for medical use in the state and Russian languages, are put into a pack of cardboard.

Storage conditions

Store in a dry, dark place at a temperature not exceeding 25°C.

Keep out of the reach of children!

Shelf life

After the first opening of the vial, the shelf life is 6 months.

Do not use the drug after the expiration date.

Terms of dispensing from pharmacies

On prescription

Manufacturer

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

Registration certificate holder

OOO Valeant, Russia

Address of the organization accepting claims from consumers on the quality of products on the territory of the Republic of Kazakhstan

Representative office of Valeant LLC in the Republic of Kazakhstan

Kazakhstan, 050059, Almaty, Al-Farabi Avenue, 17, Business Center "Nurly-Tau" Block 4B, office 1104

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

Email: About [email protected]

Attached files

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Self-regulation systems in the child's body are imperfect, therefore, at an early age, the child may experience increased convulsive activity. To combat such conditions, small patients are prescribed valproic acid preparations. "Konvuleks" syrup is able to stop anxiety manifestations, as well as epileptic seizures or related changes in the condition and personality of the patient. Most often, this form of the drug is used in pediatrics, but it can be recommended for patients of any age. The product is prescribed by a doctor, applied according to an individual scheme. Before starting therapy, you should read the instructions, take into account the features of the drug.

The syrup relieves anxiety and epileptic seizures.

Composition and active substance

Syrup "Konvuleks" has the appearance of a thick liquid without color or with a yellowish tint. It has a peach aroma and no unpleasant taste, making the composition easy to give to children. The product is placed in a dark glass bottle, a measuring syringe is attached to it.

The main active ingredient is valproic acid in the form of sodium valproate.

For 1 ml of the liquid composition, there are 50 mg of the active substance. The composition of the product includes a number of additional compounds that give it the desired chemical and physical characteristics.

Pharmacological properties

There are several hypotheses for the mechanism of action of valproic acid in children or adults. According to one of them, the substance affects the state of postsynaptic receptors, potentiating the inhibitory effect of GABA. Such a direct effect is possible due to a change in the permeability of potassium.

According to the second hypothesis, the antiepileptic effect is the result of blocking the properties of the GABA transferase enzyme, which leads to an increase in the concentration of GABA in the tissues of the central nervous system. In any case, the use of syrup "Konvuleks" leads to the blocking or prevention of convulsive activity. In parallel, there is an improvement in the patient's mood, the normalization of his psycho-emotional state.

"Convulex" is the drug of choice for children and adults with such pathologies:

epilepsy of any form and severity;
behavioral disorders and psycho-emotional disorders against the background of epilepsy;
convulsions and tics in children that occur against a background of high temperature;
epileptic seizures of various origins;
bipolar disorder in manic-depressive syndrome.

The medicine will help with epilepsy of any form and severity.

The main substance in the syrup "Konvuleks" in a short time and almost completely absorbed by the mucosa of the digestive tract. The maximum concentration of valproate in the blood plasma is fixed after 3-4 hours, food intake does not change the performance. The therapeutic effect is observed on the 2-4th day of therapy, which depends on the intervals between doses of the composition. The drug is processed by the liver, its metabolites are excreted by the kidneys, feces and lungs in less than 24 hours.

From what age is allowed

The dosage form of the drug "Convulex" in the form of a syrup is intended for children, but it can also be used in the treatment of adults. The drug is given to patients older than 3 months as prescribed by a doctor. This type of medication is considered optimal for treating babies under 6 years old. Often, the product is given to a child until he reaches the age of 11.

After that, it is transferred to other dosage forms of the composition. This is especially convenient when an increase in the daily dosage of the drug is required.

Dosage and administration

The use of Konvuleks syrup is not associated with food intake. The liquid is taken with a measuring syringe in accordance with the dosage, given to the child. It is recommended to drink the composition with a small amount of water. The doctor calculates the daily and single volume of the medicine in accordance with the diagnosis, the goals of therapy, the age and weight of the baby.

The use of syrup is not associated with food intake.

Instructions for use syrup "Konvuleks":

with a child weighing from 7.5 to 25 kg - the volume of the daily dose depends on the weight and type of problem. The amount is selected according to the formula 15-45 mg of the active substance per 1 kg of body weight. It is important not to confuse this indicator with milliliters, the latter are calculated in accordance with the concentration of the composition;
the maximum daily amount of the composition for a child weighing less than 25 kg should not exceed 50 mg per 1 kg of weight. With combination therapy, this indicator in rare cases is brought up to 100 mg per 1 kg of weight;
with a child weighing from 25 kg - the dosage is selected individually, starting with 300 mg of the active substance per day. Within 1-2 weeks, this figure is gradually increased, the step size is set by the doctor. This is done until the desired effect is achieved in the form of relief of seizures;
the maximum daily amount of the composition for a child weighing more than 25 kg should not exceed 30 mg per 1 kg of weight. When monitoring the concentration of valproate in the patient's blood, this figure can be increased to 60 mg per 1 kg of weight;
with reduced kidney function - the standard dose is reduced individually, based on laboratory parameters and the patient's response to the medication.

The dose of the drug is selected individually, starting with 300 mg per day.

The volume of the daily dose is divided into 2-3 approaches, depending on the doctor's recommendations. In most cases, therapy based on Konvuleks syrup continues for years. In situations where there are no alarming manifestations of the disease for 2-3 years, the question of stopping drug treatment is raised. Refusal of the drug is carried out gradually, according to an individual scheme.

A sharp cessation of its reception threatens the resumption of seizures.

Side effects

Subject to the rules of taking the medicine, a negative response of the body rarely occurs. The likelihood of side effects increases in the case of combination therapy or against the background of exceeding the recommended dosages of the product.

The likelihood of adverse reactions increases if combined therapy is carried out.

Possible adverse reactions to Konvuleks syrup:

dyspeptic - nausea and vomiting, abdominal pain, increased appetite or lack of it, loose stools. Very rarely, in severe cases, hepatitis, pancreatitis may develop;
neurological - trembling of the limbs, double vision, a decrease in the quality of vision due to the flickering of "flies". Very rarely and more often in children there are signs of personality changes, psycho-emotional state, mood swings. Symptoms such as headaches, daytime sleepiness, dizziness are possible. In severe cases, the drug causes confusion, fainting, coma;
metabolic - weight gain or decrease without the influence of external factors;
immune - allergic reactions of various types and intensity;
endocrine - more often manifested in adults, acquiring the appearance of the absence of menstruation or their painful course, enlargement of the mammary glands;
on the part of the hematopoietic organs - a decrease in the number of blood cells, a violation of the process of gluing platelets, an increase in bleeding time, the appearance of bruising hematomas;
others - swelling of tissues of various localization, hair loss, changes in the quality of nails.

The medicine may cause abdominal pain.

Any side effects in children require medical evaluation, regardless of their severity. Independent decision to refuse the product or continue therapy threatens with dangerous consequences.

Contraindications

The use of Konvuleks syrup is prohibited in case of serious damage to the liver and / or pancreas, hemorrhagic diathesis, porphyria. The drug is not prescribed to women in the first trimester of pregnancy and during lactation. Also, contraindications to therapy are intolerance to valproic acid and a pronounced decrease in the number of platelets in the blood.

With increased caution, the drug is used to treat babies and adults with any history of liver and / or pancreas pathologies.

Also, restrictions on drug therapy are imposed for bone marrow lesions, kidney disease, organic diseases of the central nervous system, enzymopathies. The decision on the possibility of using Konvuleks syrup for the treatment of a child with mental retardation is made by the doctor.

The drug is not prescribed in the first trimester of pregnancy.

drug interaction

Syrup "Konvuleks" often becomes a component of an integrated approach. It often has to be combined with other medicines. Any combination with an anticonvulsant must be made by a doctor. If you do not take into account the interaction of the product with other drugs, situations that are dangerous to health and life may arise.

In combination with other medicines, Konvuleks acts as follows:

in combination with products that depress the central nervous system, it enhances this effect, provokes depression;
exacerbates the hepatotoxic properties of drugs and chemical compounds, including ethyl alcohol;
loses effectiveness in combination with products that can lower the seizure threshold;
potentiates the action of other compounds with anticonvulsant properties, ethanol, antipsychotics, antidepressants, tranquilizers, barbiturates;
becomes more effective in combination with barbiturates by increasing the concentration of the main substance in the blood;
stimulates the action of indirect anticoagulants and antiplatelet agents.

In combination with products that depress the central nervous system, the drug enhances their effect and provokes depression.

The chemically active agent does not reduce the effectiveness of oral contraceptives, but against the background of hormonal therapy, its dosage may need to be adjusted. The drug does not affect the nature of the action of liver enzymes.

Analogues

A doctor should select a replacement for Konvuleks syrup, taking into account the patient's reaction to this product and the characteristics of the situation. Depending on the age of the patient and the goals of therapy, the specialist may prescribe one of the many products based on valproic acid. The most common are various types and dosage forms of the drug Depakin, Valparin or Enkorat. With intolerance to valproic acid, antiepileptic compounds from other groups are selected, the number of which is in the tens.

Valparin acts as an analogue.

Overdose

When using syrup, you need to clearly navigate the volume and concentration of the drug. Confusion in numbers threatens with an overdose, equally dangerous for children and adults. Signs of an emergency condition are nausea, vomiting and diarrhea, which are complemented by dizziness. In severe cases, there is a violation of breathing, a decrease in muscle tone, constriction of the pupils, dullness of reflexes, coma.

Gastric lavage is used as first aid if no more than 12 hours have passed since the moment of poisoning, and the victim has no signs of confusion. After that, the patient is prescribed the intake of enterosorbents.

In severe cases, hemodialysis, forced diuresis are indicated. Additionally, manipulations are carried out to stimulate the functions of the respiratory and cardiovascular systems.

Release form, packaging and prices

Syrup "Konvuleks" is available in bottles of tinted glass with a volume of 100 ml. Together with measuring syringes, they are placed in cardboard boxes. Depending on the region, the cost of the product ranges from 110 to 170 rubles.

Terms of dispensing from pharmacies

The product is included in list B, therefore it is dispensed from pharmacies by prescription.

Storage conditions and shelf life

The composition should be kept in the original packaging. It is stored in a dark and dry place at a temperature of 15 to 25℃. The shelf life of the product under these conditions is 5 years. If the product has changed color, texture, smell or sugared, its use is prohibited.

Antiepileptic drug.
Preparation: CONVULEX®

The active substance of the drug: valproic acid
ATX encoding: N03AG01
CFG: Anticonvulsant drug
Registration number: P No. 011170/02
Date of registration: 29.07.05
The owner of the reg. Award: GEROT PHARMAZEUTIKA GmbH (Austria)

Release form Konvuleks, drug packaging and composition.

Soft gelatin pink capsules, enteric-coated; the capsule is printed in black ink "150".

1 caps.
valproic acid
150 mg

Soft gelatin pink 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) - packs of cardboard.

Soft gelatin pink capsules, enteric-coated; Capsule printed in black ink "500".

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 pieces. - blisters (10) - packs of cardboard.

Long-acting tablets, film-coated, white, oval, biconvex, with a vanilla smell, with a dividing line and engraved "CC3" on one side; on the cross section - white.

1 tab.
sodium valproate
300 mg

Long-acting tablets, film-coated, white, oval, biconvex, with a vanilla smell, with a dividing line and engraved "CC5" on one side; on the cross section - white.

1 tab.
sodium valproate
500 mg

Excipients: citric acid monohydrate, ethylcellulose, eudragit RS30D, purified talc, anhydrous colloidal silicon, magnesium stearate, eudragit L30D, dibutyl phthalate, carmellose sodium, 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) - packs of cardboard.

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

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) flavors, purified water.

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

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

Pharmacological action Konvuleks

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 interferes with pre- and postsynaptic discharges and thereby prevents the spread of seizure activity in the CNS. In addition, in the mechanism of action of the drug, a significant role belongs to the effect of valproic acid on GABAА receptors, as well as the effect on voltage-dependent Na-channels. According to another hypothesis, valproic acid acts on 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 rapidly and almost completely absorbed from the gastrointestinal tract, oral bioavailability is about 100%. Eating does not reduce the rate of absorption. Cmax in plasma is noted after 3-4 hours. Therapeutic concentration of valproic acid in blood plasma is 50-100 mg / l.

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

Distribution

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

At plasma concentrations 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%.

The concentration values in the cerebrospinal fluid correlate with the value of the non-protein-bound fraction of the active substance. Valproic acid crosses 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 is metabolized in the liver by oxidation and conjugation with glucuronic acid.

breeding

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

Pharmacokinetics of the drug.

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 may 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 a decrease in the binding of the active substance to serum albumin, an increase in plasma levels of unbound drug is possible.

Indications for use:

Epilepsy of any origin;

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

epilepsy-related behavioral disorders;

Febrile seizures in children;

Manic-depressive syndrome with a bipolar course, not amenable to treatment with lithium or other drugs.

Dosage and method of application of the drug.

Adults are prescribed at 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 conducting 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 at 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 (may be increased to 60 mg / kg / 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 / day, the maximum is 50 mg / kg / day. In combination therapy - 30-100 mg / kg / day.

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

The average doses of Konvuleks in the form of capsules are presented in table 1.

Table 1
Patient's body weight (kg)
Dose (mg/day)
Number 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 Konvuleks in the form of drops and syrup are presented in table 2.

table 2
Patient's body weight (kg)
Dose (mg/day)
Amount of syrup (ml)
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
—
—

Patients with renal insufficiency may need to reduce the dose of the drug. The dose is set by monitoring the clinical condition of the patient, because. values of the concentration of valproic acid in blood plasma may not be sufficiently informative.

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

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

Capsules and tablets with prolonged action are taken without chewing, with a small amount of liquid. Drops and syrup are taken with a small amount of liquid.

Side effects of Konvuleks:

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

From the digestive system: nausea, vomiting, gastralgia, anorexia or increased appetite, diarrhea, hepatitis are possible; rarely - constipation, pancreatitis, up to severe lesions 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: possible tremor, diplopia, nystagmus, flashing "flies" before the eyes; rarely - changes in behavior, mood or mental state (depression, fatigue, hallucinations, aggressiveness, hyperactivity, psychosis, unusual agitation, restlessness or irritability), ataxia, dizziness, drowsiness, headache, dysarthria, stupor, impaired consciousness, coma .

On the part of the hematopoietic system: anemia, leukopenia, thrombocytopenia, a decrease in fibrinogen, platelet aggregation and blood clotting are possible, accompanied by an increase in bleeding time, petechial hemorrhages, bruising, hematomas, bleeding.

On the part of metabolism: a decrease or increase in body weight is possible.

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

On the part of laboratory parameters: hypercreatininemia, hyperammonemia, hyperbilirubinemia, a slight increase in 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 at the level of valproic acid in the blood plasma above 100 mg / l or with combined therapy.

Contraindications to the drug:

Severe liver dysfunction;

Severe dysfunction of the pancreas;

Porfiria;

Hemorrhagic diathesis;

Severe thrombocytopenia;

I trimester of pregnancy;

lactation (breastfeeding);

Children's age up to 3 years (for tablets with prolonged action);

Hypersensitivity to valproic acid.

With extreme caution, the drug should be prescribed with indications of a history of diseases of the liver and pancreas, bone marrow damage; with impaired renal function; patients with congenital enzymopathies; mentally retarded children; with organic brain damage; with hypoproteinemia.

Use during pregnancy and lactation.

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

In the event of pregnancy due to the risk of deterioration of the condition, treatment should not be interrupted. Convulex should be used at the lowest effective dose, avoid combination with other anticonvulsants, and regularly monitor plasma levels of valproic acid.

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

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

In experimental studies, the teratogenic effect of the drug has been established.

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 preparations.

Special instructions for the use of Konvuleks.

Patients who receive other antiepileptic drugs should be transferred to Konvuleks gradually, reaching a clinically effective dose after 2 weeks, after which other antiepileptic drugs can be gradually canceled. In patients who have not received treatment with other antiepileptic drugs, a clinically effective dose should be reached 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 the start of surgery to exclude acute pancreatitis.

It should be borne in mind that during treatment, it is possible to distort the results of urine tests in diabetes mellitus (due to an increase in the content of keto products), indicators of thyroid function.

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

The patient should be warned about the need to consult a doctor about the advisability of continuing or stopping treatment if any acute serious side effects develop.

Abrupt discontinuation of Convulex may lead to an increase in seizures.

During the period of drug use, alcohol should be avoided.

Control of laboratory parameters

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

Pediatric use

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

Influence on the ability to drive vehicles and control mechanisms

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 hypotension, hyporeflexia, miosis, coma.

Treatment: gastric lavage (no later than 10-12 hours) followed by the appointment of activated charcoal, hemodialysis. Forced diuresis, maintaining the function of breathing and the cardiovascular system.

Interaction of Konvuleks with other drugs.

Pharmacodynamic interaction

With the 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, it is possible to increase the depression of the central nervous system.

Hepatotoxic agents (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.

Convulex 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 the absence status was observed.

Pharmacokinetic interaction

With the simultaneous use of valproic acid with barbiturates or with primidone, an increase in their concentrations in blood plasma is noted. 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 up to 45-55 hours in children.

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

With simultaneous use with salicylates, an increase in the effects of valproic acid is observed due to its displacement from its association with plasma proteins. Convulex 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 (metabolism acceleration).

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

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

Conditions of sale in pharmacies.

The drug is dispensed by prescription.

Terms of storage conditions of the drug Konvuleks.

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

Prolonged-release tablets should be stored 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 (Eudragit 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, carmellose sodium, titanium dioxide (E171), purified talc, vanillin.

Description

Oval-shaped, film-coated tablets, white, with a score on one side of the score engraved "CC" 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-shaped, film-coated, white, with a score on one side of the score with the engraving "CC" 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 rapidly and almost completely absorbed from the gastrointestinal tract, oral bioavailability is 100%. Eating does not reduce the rate of absorption. The maximum level of plasma concentration is observed after 1-6 hours. The equilibrium concentration is reached on the 2-4th day 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 value of the non-protein fraction of the drug. Valproic acid crosses 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. 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 with 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 latent time of absorption, slow absorption, lower (by 25%), but relatively more stable plasma concentration between 4 and 14 hours.

Pharmacodynamics

Convulex is an antiepileptic agent, also has a central muscle relaxant and sedative effect. The mechanism of action is due mainly 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 thus prevents the spread of seizure activity in the CNS. In addition, in the mechanism of action of the drug, a significant role belongs to 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, imitating or enhancing the inhibitory effect of GABA. A possible direct effect on membrane activity is associated with changes in potassium conductivity. Improves the mental state and mood of patients, has antiarrhythmic activity.

Indications for use

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

Bipolar manic-depressive disorder when lithium is contraindicated or not tolerated by the patient

Dosage and administration

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 of body weight.

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

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

The dosage in 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 above 40 mg/kg per day, biochemical and haematological parameters should be monitored.

Elderly age

Although the pharmacokinetics of valproate in the elderly has its own characteristics, this is of limited clinical significance, and the dose should be determined by the clinical effect. Due to the decrease in 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 lower doses of the drug.

Patients with renal insufficiency

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

Average daily doses:

Side effects

Side effects are possible mainly at the level of the drug in plasma above 100 mg / l or in combination therapy.

Often (from ³1/100 to<1/10 случаев)

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

Diplopia, flashing "flies" before the eyes

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

Decrease or increase in body weight

Hypercreatininemia, hyperammonemia, hyperglycinemia, hyperbilirubinemia, a 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 loss, paresthesia

Polycystic ovaries

Enuresis in children

Rare (³1/10,000 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 for 2-12 weeks)

Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme

Reversible Fanconi syndrome

bone marrow aplasia

Hyponatremia

Impaired kidney function

Contraindications

Hypersensitivity to valproate or any of the excipients

Severe disorders 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 that associated with taking medications

Thrombocytopenia

Hemorrhagic diathesis

Combined administration with carbapenems

Combined reception with St. John's wort

Combination with mefloquine

Children's age up to 6 years

Pregnancy and lactation

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

Drug Interactions

Valproate can increase the concentration of zidovudine in the blood plasma, which will lead to an increase in the toxicity of the latter.

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

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

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 hepatic enzymes and does not reduce the effectiveness of oral contraceptives.

special instructions

Special care is required when prescribing Konvuleks to the following categories of patients:

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

With impaired renal function

With congenital enzymopathies

Mentally retarded children

With hypoproteinemia

During the period of treatment with the drug, alcohol is not allowed. Suicidal ideation and behavior has been reported among patients treated with antiepileptic drugs for some indications. The mechanism by which this risk occurs remains unknown, and the available data do not exclude the possibility of an increased risk due to the use of valproic acid.

For liver disorders

For hematological disorders

For disorders of the pancreas

For diabetes

Weight gain

Hyperammonemia

If there is suspicion of enzymatic deficiency of the urea cycle, metabolic studies should be carried out before starting treatment, since there is a risk of hyperammonemia when using valproate.

With the development of any acute serious side effects, it is necessary to immediately discuss with the 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.

Abrupt discontinuation of Convulex may lead to an increase in epileptic seizures.

Doses greater than 1000 mg/day and combination with other anticonvulsants are important risk factors for fetal malformations.

Current epidemiological data do not indicate a decrease in the general intelligence quotient of children with exposure to sodium valproate.

When planning a pregnancy

If you plan to become pregnant, you should definitely decide on the use of other medications.

During pregnancy

Before delivery, a coagulogram should be done, in particular, the number of platelets, the level of fibrinogen and the time of blood clotting (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 influence of the drug on the ability to drive a vehicle or potentially dangerous mechanisms