Convulex, pills 300mg, 50pcs

Composition

of 1 tab. :

– sodium valproate 300 mg.

Auxiliary substances:

citric acid,

ethylcellulose,

copolymer of methyl methacrylate,

trimethylammonioethyl methacrylate chloride and ethyl acrylate (1: 2: 0.1) (eudragite RS30D),

purified talc,

colloidal anhydrous silicon,

magnesium stearate.

Pharmacological action

Pharmaceutical Group:

antiepileptic drug

Pharmaceutical action:

 Convulex is an antiepileptic drug.

It also has a central muscle relaxant and sedative effect.

The mechanism of action is mainly due to an increase in the content of GABA in the central nervous system due to inhibition of the enzyme GABA-transferase. GABA reduces excitability and convulsive readiness of motor areas of the brain. In addition, the effect of valproic acid on GABAA receptors (activation of gabaergic transmission), as well as the effect on potential-dependent sodium channels, plays a significant role in the mechanism of action of the drug.

According to another hypothesis, it acts on areas of postsynaptic receptors, mimicking or enhancing the inhibitory effect of GABA. A possible direct effect on membrane activity is related to changes in the conductivity of potassium ions. Improves the mental state and mood of patients, has antiarrhythmic activity.

Pharmacokinetics:

 Absorption Valproic acid is almost completely absorbed from the gastrointestinal tract, bioavailability when taken orally is 100%. Food intake does not reduce the rate of absorption. Cmax in blood plasma after taking long-acting tablets is reached in 4 hours, Cmax in blood plasma after taking oral drops – in 1-3 hours. The therapeutic concentration of valproic acid in blood plasma is 50-150 mg/l.

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

The distribution of CSSS is achieved on day 2-4 of treatment, depending on the intervals between doses. At a plasma concentration 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%.

The values of the concentration in the cerebrospinal fluid correlate with the value of the non-protein fraction of the Active ingredient. Valproic acid penetrates the placental barrier and is excreted in breast milk. The concentration in breast milk is 1-10% of the concentration in the mother’s blood plasma.

Metabolism Valproic acid undergoes glucuronidation and oxidation in the liver.

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

Pharmacokinetics in special clinical cases

In 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.

Indications

-epilepsy of various etiologies (idiopathic, cryptogenic and symptomatic);- generalized epileptic seizures in adults and children (clonic, tonic, tonic-clonic, absences, myoclonic, atonic);- partial epileptic seizures in adults and children (with or without secondary generalization);- specific syndromes (West, Lennox-Gastaut);- behavioral disorders caused by epilepsy;— febrile seizures in children, children’s tic; – treatment and prevention of bipolar affective disorders (for oral drops);- treatment and prevention of bipolar affective disorders that are resistant to treatment with lithium or other medications (for long-acting tablets).

Contraindications

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

Side effects

In general, Convulex® is well tolerated in patients. Side effects are possible mainly with a plasma concentration of the drug above 100 mg / l or with combination therapy.

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

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

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

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

Endocrine disorders: dysmenorrhea, secondary amenorrhea, breast enlargement, galactorrhea.

From the laboratory parameters: hypercreatininemia, hyperammonemia, hyperbilirubinemia, a slight increase in the activity of hepatic transaminases, LDH (dose-dependent).

Allergic reactions: skin rash, urticaria, angioedema, photosensitization, malignant exudative erythema (Stevens-Johnson syndrome).

Other: peripheral edema, hair loss (usually recovers after discontinuation of the drug). Overdose: Symptoms: nausea, vomiting, dizziness, diarrhea, respiratory failure, muscle hypotension, hyporeflexia, miosis, coma.

Treatment: gastric lavage (no later than 10-12 hours), followed by the appointment of activated charcoal, hemodialysis. Forced diuresis, maintenance of vital functions.

Interaction

-Contraindicated combinations of mefloquine: the risk of epileptic seizures due to increased metabolism of valproic acid and a decrease in its concentration in plasma and, on the other hand, the convulsant effect of mefloquine.

St. John’s wort: the risk of reducing 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 responsible for lamotrigine 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 blood plasma. If a combination is necessary, careful clinical and laboratory monitoring is required. – Combinations that require special precautions

Carbamazepine: valproic acid increases the concentration of the active metabolite of carbamazepine in plasma until signs of overdose. In addition, carbamazepine increases the hepatic metabolism of valproic acid and reduces its concentration. These circumstances require the doctor’s attention and determination of the drug concentrations in plasma and possible revision of their doses.

Phenobarbital, primidone: valproic acid increases the concentration of phenobarbital or primidone in plasma until signs of overdose, more often in children. In turn, phenobarbital or primidone increases the hepatic metabolism of valproic acid and reduces its concentration. Clinical monitoring is recommended during the first 2 weeks of combined treatment with immediate reduction of the dose of phenobarbital or primidone if signs of sedation appear, and determination of the level of anticonvulsants in the blood.

Phenytoin: changes in the concentration of phenytoin in plasma are possible, phenytoin increases the hepatic metabolism of valproic acid and reduces its concentration. It is recommended to conduct clinical monitoring, determine the level of anticonvulsants in the blood, and change the dosage if necessary.

Clonazepam: the addition of valproic acid to clonazepam in isolated cases may lead to an increase in the severity of the absent status.

Ethosuximide: valproic acid can both increase or decrease the concentration of ethosuximide in the blood serum due to changes in its metabolism. It is recommended to conduct clinical monitoring, determine the level of anticonvulsants in the blood, and change the dosage if necessary.

Topiramate: increases the risk of hyperammonemia and encephalopathy.

Felbamate: increased plasma valproic acid concentrations by 35-50%, with a risk of overdose.It is recommended to conduct clinical monitoring, determine the level of valproic acid in the blood, and change the dosage of valproic acid when combined with felbamate and after its withdrawal.

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

Cimetidine, erythromycin: inhibit hepatic metabolism of valproic acid and increase its concentration in plasma.

Zidovudine: valproic acid increases the concentration of zidovudine in plasma, which leads to an increase in its toxicity. Carbapenems, monobactams: meropenem, panipenem, as well as aztreonam and imipenem reduce the concentration of valproic acid in plasma, which can lead to a decrease in the anticonvulsant effect.

– Combinations that should be taken into account

Acetylsalicylic acid: increased effects of valproic acid due to its displacement from plasma protein binding. 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: an increase in the hypotensive effect of nimodipine due to an increase in its plasma concentration due to suppression of its metabolism by valproic acid.

Myelotoxic drugs: increased risk of inhibition of bone marrow hematopoiesis. Ethanol and hepatotoxic drugs: increase the likelihood of developing liver damage.

– Other combinations

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

How to take, course of use and dosage

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

Drops for oral use are taken orally 2-3 times/day, regardless of food intake, with a small amount of water. Adults are prescribed an initial dose of 600 mg / day. with a gradual increase every 3 days until the clinical effect (disappearance of seizures) is achieved.

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 recommended daily dose is about 1-2 g, i. e. 20-30 mg/kg. If necessary, the dose can be increased to 2.5 g / day. (30 mg / kg / day). The maximum dose is 30 mg / kg / day. (in patients with accelerated valproic acid metabolism, the maximum dose may be increased to 60 mg / kg / day. under the control of the concentration of valproic acid in blood plasma).

In combination therapy, the dose is 10-30 mg / kg / day. with a subsequent increase of 5-10 mg / kg per week. Children with a body weight of more than 25 kg are prescribed an initial dose of 300 mg / day (5-15 mg / kg/day), with a gradual increase of 5-10 mg/kg per week until the clinical effect (disappearance of seizures) is achieved, while the dose is usually 1-1.5 g/day (20-30 mg/kg/day).

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

For children with a body weight of 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. Please note that children with a body weight of less than 20 kg are not recommended to use the drug in the form of long-acting tablets, they should use other forms of the drug.

Special instructions

Due to reports of severe and fatal cases of hepatic insufficiency and pancreatitis, the following should be taken into account when using valproic acid preparations::

– the increased risk group consists of children 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 function disorders developed in the first 6 months (usually between 2 and 12 weeks) of treatment, more often with combined antiepileptic treatment;— cases of pancreatitis were observed regardless of the patient’s age and duration of treatment, although the risk of developing pancreatitis decreased with the patient’s age;— liver failure in pancreatitis increases the risk of death;— early diagnosis (up to the icteric stage) is based mainly on clinical observation – detection of early symptoms, such as asthenia, anorexia, extreme fatigue, drowsiness, sometimes accompanied by vomiting and abdominal pain; at the same time, there may be a relapse of epileptic seizures permanent 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 hepatic transaminases, the level of prothrombin, fibrinogen, clotting factors, bilirubin concentration, as well as amylase activity (every 3 months, especially when combined with other antiepileptic drugs) and the picture of peripheral blood, in particular, blood platelets. 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 the gradual withdrawal of other antiepileptic drugs is possible. In patients who have not been treated with other antiepileptic drugs, the clinically effective dose should be reached after 1 week.

The risk of liver side effects 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 count), determination of bleeding time, and coagulogram 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 surgery to exclude acute pancreatitis.

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

If any acute, serious side effects develop, you should immediately discuss with your doctor whether to continue or discontinue treatment.

To reduce the risk of developing dyspeptic disorders, it is possible to take antispasmodics and enveloping agents. Abrupt discontinuation of Convulex can lead to an increase in epileptic seizures.

Influence on the ability to drive motor vehicles and manage mechanisms

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

Form of production

Long acting coated tablets

Active ingredient

Valproic Acid

Conditions of release from pharmacies

By prescription

Dosage form

Tablets