Convulex - instructions for use, dose, side effects, contraindications

Excipients: citric acid 39.0 / 65.0 mg, ethylcellulose 60.0 / 100.0 mg, methyl methacrylate trimethylammonioethyl methacrylate chloride, ethyl acrylate copolymer (1: 2: 0.1) (Eudragit RS30D) 20.1 / 33.5 mg, talc 8.1 / 13.5 mg, silicon dioxide colloid 6.0 / 10.0 mg, magnesium stearate 6.0 / 10.0 mg;

shell: methyl methacrylate trimethylammonioethyl methacrylate chloride, ethyl acrylate copolymer (1: 2: 0.2) (Eudragit RL30D type A) 2.25 / 3.2 mg, methyl methacrylate trimethylammonioethyl methacrylate chloride, ethyl acrylate copolymer (1: 2: 0.1) (Eudragit RS30D ) 2.25 / 3.2 mg, triethyl citrate 0.9 / 1.28 mg, carmellose sodium 1.27 / 1.8 mg, titanium dioxide 1.06 / 1.5 mg, talc 2.02 / 2.87 mg , vanillin 0.11 / 0.15 mg.

Description:

Oval, biconvex tablets of white color, film-coated, with a fault line and engraving "CC3" (for 300 mg tablets) and "CC5" (for tablets 500 mg) on the one hand, with the smell of vanillin. On the fracture: white or almost white.

Pharmacotherapeutic group:Antiepileptic remedy

ATX: & nbsp

N.03.A.G.01 Valproic acid

Pharmacodynamics:

CONVULX ® is an anti-epileptic, has a central muscle relaxant and sedative effect.

The mechanism of action is mainly due to an increase in the content of gamma-aminobutyric acid (GABA) in the central nervous system (CNS) due to inhibition of the enzyme GABA transferase. GABA reduces excitability and convulsive readiness of motor zones of the brain. Further, in the mechanism of action of the drug plays a significant role in the effects of valproic acid GABA A receptors, as well as the effect on voltage-sensitive sodium channels. According to another hypothesis, it acts on the sites of postsynaptic receptors, imitating or enhancing the inhibitory effect of GABA. Possible direct influenceYanie on membrane activity is associated with changes in conductivity for potassium ions. It improves the mental state and mood of patients, has antiarrhythmic activity.

Pharmacokinetics:

Valproic acid is almost completely absorbed in the gastrointestinal tract, bioavailability when ingested is 100%. Eating does not reduce the absorption rate. The maximum level of plasma concentration is noted 4 hours after the administration of long-acting tablets. The equilibrium concentration is achieved on the 2nd-4th day of treatment, depending on the intervals between doses.The therapeutic concentration of the drug in the blood plasma varies between 50-150 mg / l. Connection with plasma proteins - 90-95% at a concentration in the blood plasma to 50 mg / l and 80-85% at a concentration of 50-100 mg / l.

With uremia, hypoproteinemia and liver cirrhosis, binding to plasma proteins is reduced.

Concentration in the cerebrospinal fluid correlates with the value of the protein-free fraction of the drug.

Valproic acid penetrates the placental barrier and the blood-brain barrier, excreted in breast milk. Concentration in breast milk is 1-10% concentration in the blood plasma of the mother.

The drug is subjected to 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 with exhaled air.

The half-life (T_1/2) of the drug is in healthy subjects and in monotherapy from 8 to 20 hours, when combined with drugs that induce enzymes involved in the metabolism of valproic acid, T_1/2can be 6-8 hours, in patients with impaired liver function and elderly patients and children under 18 months can be significantly longer.

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

Indications:

- Epilepsy of various etiologies - idiopathic, cryptogenic and symptomatic;

- generalized epileptic seizures in adults and children: clonic, tonic, tonic-clonic, absences, myoclonic, atonic;

- partial epileptic seizures in adults and children: with or without secondary generalization;

- Specific syndromes (Vesta, Lennox-Gastaut);

- Disorders of the nature and behavior caused by epilepsy;

- febrile convulsions in children, children's teak;

- bipolar affective disorders, which can not be treated with lithium or other drugs - treatment and prevention.

Contraindications:

- Hypersensitivity to valproic acid and its salts or components of the drug;

- liver failure;

acute and chronic hepatitis;

- impaired pancreatic function;

- porphyria;

- hemorrhagic diathesis;

- severe thrombocytopenia;

- violation of the exchange of the urea cycle (including in the family history);

- lactation period;

- Children weighing less than 20 kg;

- Children's age (up to three years).

Carefully:

The purpose of CONVUX® is as follows:

- with anamnestic data on liver and pancreas diseases;

- with oppression of bone marrow hematopoiesis (leukopenia, thrombocytopenia, anemia);

- with renal insufficiency;

- with congenital fermentopathy;

- children with mental retardation;

- with organic diseases of the brain;

- with hypoproteinemia;

- pregnancy (especially I trimester).

Dosing and Administration:

CONVULX® is taken orally, without chewing, 1-2 times a day, during or immediately after a meal, with a small amount of water.

Adults. The initial daily dose is 600 mg, with a gradual increase in the dose of 150-250 mg every three days until the clinical effect (disappearance of seizures) is reached.

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

The recommended daily dose is about 1000-2000 mg per day, i.e. 20-25 mg / kg, if necessary, the dose may be increased to a maximum dose of 2500 mg per day (30 mg / kg body weight).

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

When combined therapy - 10-30 mg / kg / day with a subsequent increase in the dose of 5-10 mg / kg / week.

Children with a body weight of more than 25 kg. The initial daily dose is 300 mg (5-15 mg / kg / day), with a gradual increase in the dose (by 5-10 mg / kg / week) until the clinical effect (disappearance of convulsive seizures), which is usually 1000-1500 mg in day (20-30 mg / kg / day). The maximum dose of 30 mg / kg / day (in patients with accelerated metabolism of valproic acid, identifiednnthe maximum dose can be increased to 60 mg / kg / day).

Children with a body weight of 20-25 kg. The average daily dose for monotherapy is 15-45 mg / kg, the maximum is 50 mg / kg. When combined therapy - 30-100 mg / kg / day.

Children with body weight less than 20 kg should be recommended for taking other dosage forms of the drug.

Elderly age. Although the pharmacokinetics of valproic acid in the elderly may have its own peculiarities, this is of limited clinical importance, and the dose should be determined by the clinical effect. Due to a decrease in binding to serum albumin, the proportion of unbound preparation in plasma increases.This causes the expediency of a more careful selection of the dose of the drug in the elderly, with the possible use of smaller doses of the drug.

Patients with renal insufficiency. It may be necessary to reduce the dose of the drug. The dose should be selected by monitoring the clinical state, since plasma concentrations may not be sufficiently informative.

Side effects:

In general, CONVULX® is well tolerated by patients.

Side effects are possible mainly at a drug concentration in the plasma above 100 mg / l or with combined therapy.

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

Central nervous system: tremor, changes in behavior, mood or mental state (depression, fatigue, hallucinations, aggressiveness, hyperactive state, psychoses, unusual agitation, motor anxiety or irritability), ataxia, dizziness, drowsiness, headache, encephalopathy, dysarthria, enuresis, stupor, impaired consciousness, coma.

From the sense organs: diplopia, nystagmus, flashing of "flies" before the eyes.

On the part of the organs of hematopoiesis and the system of hemostasis: anemia, leukopenia; thrombocytopenia, decreased fibrinogen and platelet aggregation leading to the development of hypocoagulation (accompanied by prolonged bleeding time, petechial hemorrhages, bruising, bruising, bleeding).

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

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

Laboratory indicators: hyperkreatininemia, hyperammonemia, hyperbilirubinemia, hyperglycinemia, a slight increase in the activity of "hepatic" transaminases, lactate dehydrogenase (dose-dependent).

From the endocrine system: dysmenorrhea, secondary amenorrhea, enlargement of mammary glands, galactorrhea.

Other: peripheral edema, hair loss (as a rule, is restored after drug discontinuation).

Overdose:

Symptoms: nausea, vomiting, dizziness, diarrhea, violation of respiratory function, muscle hypotension, hyporeflexia, miosis, coma.

Treatment: gastric lavage (not later than 10-12 hours), activated charcoal, hemodialysis, forced diuresis, maintenance of vital functions.

Interaction:

Valproic acid enhances effects, including side effects, of other antiepileptic drugs (phenytoin, lamotrigine), antidepressants, antipsychotic drugs (antipsychotics), anxiolytics, barbiturates, monoamine oxidase (MAO) inhibitors, thymoleptics, ethanol.

Addition of valproic acid to clonazepam in single cases can lead to an increase in the expression of absent status.

With the simultaneous use of valproic acid with barbiturates or primidone, there is an increase in the concentration of the latter in the blood plasma.

Increases T_1/2 lamotrigine (inhibits the enzymes of the liver, causes a slowing down of the metabolism of Lamirinum laminas, as a result of which T_1/2 it lengthens to 70 hours in adults and up to 45-55 hours in children).

Reduces zidovudine clearance by 38%, while its T_1/2 does not change.

Tricyclic antidepressants, MAO inhibitors, antipsychotics (antipsychotics) and other drugs that reduce the threshold of seizure activity, reduce the effectiveness of the drug.

With simultaneous reception of the preparation of Convulex® with ethanol and other drugs depressing the work of the central nervous system (tricyclic antidepressants, MAO inhibitors, antipsychotic drugs), an increase in CNS depression is possible.

When combined with salicylates, there is an increase in the effects of valproic acid (displacement of plasma from the protein).

Convullex® enhances the effect of antiplatelet agents (acetylsalicylic acid) and indirect anticoagulants.

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

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

Myelotoxic drugs - increased risk of oppression of bone marrow hematopoiesis.

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

Ethanol and hepatotoxic drugs increase the likelihood of developing liver damage.

Valproic acid can both increase and decrease the concentration of ethosuximide in the blood serum due to changes in metabolism.

Meropenem reduces the concentration of valproic acid in the plasma, which can lead to a decrease in the anticonvulsant effect.

With simultaneous application with topiramate, the risk of hyperammonemia and encephalopathy increases.

Special instructions:

During treatment, it is advisable to monitor the activity of "liver" transaminases, bilirubin concentrations, peripheral blood picture, blood platelets, the state of the blood coagulation system, the activity of amylase (every 3 months, especially when combined with other antiepileptic drugs).

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

The risk of developing side effects from the liver is increased when combined anticonvulsant therapy, as well as in children.

Do not drink beverages that contain ethanol.

Before a surgical intervention, a general blood test is necessary (incl.number of thrombocytes), determination of bleeding time, coagulogram indices.

If there is a symptomatology of the "acute" abdomen before the onset of surgery, it is recommended to determine the activity of amylase in the blood to exclude acute pancreatitis.

During treatment it is necessary to take into account the possible distortion of the results of urinalysis in diabetes mellitus (due to an increase in the content of ketone bodies), thyroid function indices.

With the development of any acute serious side effects, it is necessary to immediately discuss with the doctor the advisability of continuing or discontinuing treatment.

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

A sharp discontinuation of taking CONVULEX® can lead to an increase in epileptic seizures.

Effect on the ability to drive transp. cf. and fur:

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

Form release / dosage:Tablets of prolonged action, film-coated, 300 mg and 500 mg.

Packaging:

For 50 or 100 tablets in a bottle of dark glass, hydrolytic stability type III (Hearth.F.), with a lid of high density polyethylene of white color, with or without a drying capsule built into the lid, controlled by the first opening. 1 bottle with instructions for use in a cardboard box.

For 50 or 100 tablets in a cylindrical container (bottle) of high density polyethylene of white color, with a lid of low density polyethylene with control of the first opening. 1 bottle with instructions for use in a cardboard box.

For 50 or 100 tablets in a cylindrical container (bottle) made of polypropylene, with a lid of low density polyethylene with a control of the first opening, with or without a drying capsule built into the lid. 1 bottle with instructions for use in a cardboard box.

Storage conditions:

In a dry place, in tightly closed containers, at a temperature of no higher than 25 ° C.

Keep out of the reach of children

Shelf life:

5 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:П N015315 / 01

Date of registration:29.05.2009 / 08.06.2017

Expiration Date:Unlimited

The owner of the registration certificate:VALEANT, LLC VALEANT, LLC Russia

Manufacturer: & nbsp

G.L.PHARMA, GmbH Austria

Representation: & nbspVALEANT LLC VALEANT LLC Russia

Information update date: & nbsp03.02.2018

Illustrated instructions

Instructions

Convullex® (Convulex®)