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

body composition of the capsule: * Caryon 83 (dry matter) 15.14 / 24.94 / 40.97 mg, glycerol 85% 21.63 / 35.63 / 58.53 mg, gelatin 71.56 / 117.86 / 193.64 mg , titanium dioxide 0.67 / 1.10 / 1.81 mg, iron oxide dye red 0.17 / 0.28 / 0.46 mg, hydrochloric acid 25% 0.57 / 0.94 / 1.54 mg,

enteric coating capsule: ** methacrylic acid and ethyl acrylate copolymer (1: 1) dispersion 30% dry 17.55 / 28.83 / 47.62 mg, triethyl citrate 2.81 / 4.61 / 7.62 mg, macrogol 60000.88 / 1 , 44 / 2.38 mg, glyceryl monostearate 45-55 type II 0.53 / 0.86 (1.43 mg;

* Carion 83 consists of: 2-4% mannitol, 27-35% sorbitol, 61-71% hydrogenated starch.

** Contains also 0.7% sodium lauryl sulfate, corresponds to 0.12 mg / capsule or 0.04% w / w from the weight of the capsule and 2.3% polysorbate 80 corresponds to 0.4 mg / capsule or 0.14% w / w based on weight capsules

Description:

Soft gelatin capsules in pink color, coated with enteric coating.

The contents of the capsules are colorless or colorless with a slightly yellowish tinge, with a weak characteristic odor.

Pharmacotherapeutic group:Antiepileptic remedy

ATX: & nbsp

N.03.A.G.01 Valproic acid

Pharmacodynamics:

CONVULX ® is an antiepileptic remedy, 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. In addition, the action of valproic acid on the GABA A receptors (activation of GABA-ergic transmission), as well as the effect on the potential-dependent sodium channels. According to another hypothesis, it acts on the sites of postsynaptic receptors, imitating or enhancing the inhibitory effect of GABA. Possible direct influence 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, the bioavailability with ingestion is 100%. Eating does not reduce the absorption rate. The maximum level of plasma concentration is noted 2-3 hours after taking the capsules.The equilibrium concentration is achieved on the 2nd-4th day of treatment, depending on the intervals between doses. The therapeutic concentration of valproic acid in blood plasma ranges from 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.

The concentration in the cerebrospinal fluid correlates with the value not associated with the plasma proteins of the valproic acid fraction.

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.

Valproic acid 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) 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, 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.

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);

- Behavioral disorders due to epilepsy;

- febrile convulsions in children, children's teak;

- treatment and prevention of bipolar affective disorders.

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;

- Disorders of urea metabolism (including in family history);

- combination with mefloquine, St. John's wort, perforated, lamotrigine;

- lactation period;

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

Carefully:

The purpose of CONVUX® is as follows:

- with anamnestic data on liver and pancreas diseases (including in family history);

- 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).

Pregnancy and lactation: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 taking valproate in the first trimester of pregnancy is 1-2%. It is advisable in this regard, the use of folic acid preparations. In the first trimester of pregnancy, do not start treatment with KONVOLEKSOM®. If the pregnant woman is already receiving the drug, then due to the risk of more seizures, treatment should not be interrupted. The drug should be used in the lowest effective doses, avoiding the combination with other anticonvulsants and, if possible, regularly monitoring the concentration of valproic acid in the plasma.

Dosing and Administration:

CONVULX® is taken orally, without chewing, 2-3 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.

Initial dose with monotherapy - 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 (y patients with the 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).

With combined therapy - 10-30 mg / kg / day, followed by an 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 per day (20-30 mg / kg / day).

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

Children with a body weight of 7.5-25 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.

Average daily doses:

Weight of the patient, 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

Elderly age: although the pharmacokinetics of valproic acid in the elderly may have its own peculiarities, it 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; 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 rash, hives, 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 the mammary glands, galactorrhea.

Other: peripheral edema, hair loss (usually restored after the drug is discontinued).

Overdose:

Symptoms: nausea, vomiting, dizziness, diarrhea, impaired breathing 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:

Contraindicated combinations:

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

- St. John's wort - risk of lowering the concentration of valproic acid in blood plasma.

Unrecommended combinations:

- lamotrigine - An increased risk of severe skin reactions (toxic epidermal necrolysis). Valproic acid inhibits microsomal liver enzymes that provide lamotrigine metabolism, which slows down its T_1/2 up to 70 hours in adults and up to 45-55 hours in children and increases the concentration in the blood plasma. If a combination is necessary, careful clinical and laboratory testing is required.

Combinations, requiring special precautions:

- carbamazepine - valproic acid increases the concentration of the active metabolite of carbamazepine in plasma to signs of overdose. Besides, carbamazepine enhances the hepatic metabolism of valproic acid and reduces its concentration. These circumstances require the attention of the doctor and the determination of the concentrations of the drugs in the plasma and the possible revision of their dosages;

- phenobarbital, primidon - valproic acid increases the concentration of phenobarbital or primidone in the plasma to signs of an overdose, more often in children. In its turn, phenobarbital or primidon 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, the level of anticonvulsants 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. Clinical observation is recommended, the level of anticonvulsants in the blood is determined, dosage changes are made if necessary;

- clonazepam - the addition of valproic acid to clonazepam in single cases may lead to an increase in the expression of the absences status;

- ethosuximide - valproic acid can both increase and decrease the concentration of ethosuximide in the blood serum due to a change in its metabolism. Clinical observation is recommended, the level of anticonvulsants in the blood is determined, dosage changes are made if necessary;

- topiramate - increased risk of hyperamonia and encephalopathy;

- felbamate - an increase in the concentration of valproic acid in the plasma by 35-50%, with the risk of overdose. Clinical observation, determination of valproic acid level in the blood, change in the dosage of valproic acid when combined with felbamate and after its cancellation is recommended;

- neuroleptics, monoamine oxidase (MAO) inhibitors, antidepressants, benzodiazepines - Neuroleptics, tricyclic antidepressants, MAO inhibitors, reducing the threshold of convulsive readiness, reduce the effectiveness of the drug. In its turn valproic acid potentiates the effect of these psychotropic drugs, as well as benzodiazepines;

- cimetidine, erythromycin - Suppress the hepatic metabolism of valproic acid and increase its concentration in the plasma;

- zidovudine - valproic acid increases the concentration of zidovudine in the plasma, which leads to an increase in its toxicity;

- carbapenems, monobactams - meropenem, panipenem, as well as azemon and imipenem reduce the concentration of valproic acid in the 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 the bond 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 required when co-administered with vitamin K-dependent anticoagulants;

- nimodipine - strengthening the hypotensive effect of nimodipine due to an increase in its concentration in the plasma due to the suppression of its metabolism with valproic acid;

- myelotoxic drugs - increased risk of oppression of bone marrow hematopoiesis;

- ethanol and hepatotoxic drugs - increase the likelihood of developing liver damage.

Other combinations:

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

Special instructions:

In connection with the available reports of severe and lethal cases of hepatic insufficiency and pancreatitis with the use of valproic acid preparations, it is necessary to bear in mind the following:

- At-risk groups are infants and children under 3 years old, with severe epilepsy, often associated with brain damage and congenital metabolic or degenerative diseases;

- in most cases, liver function abnormalities 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 irrespective of the patient's age and duration of treatment, although the risk of developing pancreatitis decreased with the age of the patient;

- Lack of liver function in pancreatitis increases the risk of death;

- early diagnosis (before the hysterical stage) is based mainly on clinical observation - the detection of early symptoms such as asthenia, anorexia, extreme fatigue, drowsiness, sometimes accompanied by vomiting and abdominal pain; with the recurrence of epileptic seizures against a background of unchanged antiepileptic therapy.

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

During treatment, especially in the first 6 months,it is necessary to periodically check the 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 the peripheral blood picture, in particular, blood platelets .

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 the surgical intervention, a general blood test (including platelet numbers), bleeding time, coagulogram indices is required.

If there is a symptomatology of the "acute" abdomen on the background of treatment before the beginning of an operation, it is recommendeddetermine 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:Capsules enteric, 150 mg, 300 mg and 500 mg.

Packaging:

Capsules 150 mg: For 10 or 20 capsules in a blister of PVC /Al or PVC / PVDC /Al. 10 blisters for 10 capsules or 5 blisters for 20 capsules together with instructions for use in a cardboard box.

Capsules 300 mg: For 20 capsules in a blister of PVC /Al or PVC / PVDC /Al. For 5 blisters together with instructions for use in a cardboard box.

Capsules of 500 mg: 10 capsules per blister of PVC /Al or PVC / PVDC /Al. By 3 or 10 blisters together with instructions for use in a cardboard box.

Storage conditions:At a temperature of no higher than 30 ° 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 N011170 / 03

Date of registration:10.06.2010 / 08.06.2017

Expiration Date:Unlimited

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

Manufacturer: & nbsp

CATALENT GERMANY EBERBACH Gmbh Germany

Representation: & nbspVALEANT LLC VALEANT LLC Russia

Information update date: & nbsp03.02.2018

Illustrated instructions

Instructions

Convullex® (Convulex®)