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

Pharmacodynamics:CONVULX ® is an antiepileptic agent, it also 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 voltage-dependent sodium channels, play an important role in the mechanism of action of the drug.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. It improves the mental state and mood of patients, has antiarrhythmic activity.

Pharmacokinetics:

Equilibrium concentration with intravenous administration is achieved within a few minutes and can be maintained by a slow infusion. The therapeutic concentration of valproic acid in blood plasma ranges from 50-150 mg / l. Valproic acid is associated with plasma proteins by 90-95% at a plasma concentration of up to 50 mg / l and by 80-85% at a concentration of 50-100 mg / l, with uremia, hypoproteinemia and cirrhosis, the association with plasma proteins is reduced.

The concentration in the cerebrospinal fluid correlates with the value of the valproic acid fraction not associated with the plasma proteins, amounting to about 10% of the serum value.

Valproic acid penetrates through the placental and 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, elderly patients and children under 18 months can be significantly longer.

Indications:

- 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 (Vesta, Lennox-Gastaut);

- febrile convulsions in children;

- 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;

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

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

lactation period.

Carefully:

- At children at treatment by several antiepileptic preparations;

- in children and adolescents with multiple comorbidities and with severe forms of seizures;

- with violations of kidney function;

- in patients with anamnestic data on liver and pancreas diseases;

- when oppression of bone marrow hematopoiesis; leukopenia, anemia, thrombocytopenia;

- with congenital enzymopathy;

- with organic brain lesions;

- with hypoproteinemia;

- children's age (up to 3 years);

- 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® solution for injection is used for intravenous (IV) administration. For IV administration, the recommended daily dose is 5-10 mg valproic acid per kg body weight. With IV infusion introduction, the recommended dose is 0.5-1 mg valproic acid per kg body weight per hour.

When switching from oral to IV administration, the doses are not changed, the first IV administration is recommended 12 hours after the last oral administration. The injection solution for injection should be replaced by taking the drug inside, as soon as the patient's condition allows it. The first intake is also recommended 12 hours after the last injection.

If you need to quickly achieve and maintain a high concentration in the plasma, the following approach is recommended: iv injection of 15 mg / kg for 5 minutes, after 30 minutes, start infusion at a rate of 1 mg / kg / h with constant monitoring of the concentration to achieve a plasma concentration of about 75 mcg / ml.

The maximum daily dose of the drug should not exceed 2500 mg.

The average daily doses are 20 mg / kg in adults and elderly patients, 25 mg / kg in adolescents, and 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 infusion solution can be used within 24 hours, the unused volume of the solution is destroyed. If IV drugs are used, Convoulex® should be administered by a separate infusion system.

Side effects:

In general, CONVULX® is well tolerated by patients. Side effects are possible mainly with the concentration of valproic acid 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, 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 indicatorand: hypercreatininaemia, hyperammonemia, hyperbilirubinemia, hyperglycinemia, a slight increase in the activity of "hepatic" transaminases, lactate dehydrogenase (dose-dependent).

From the endocrine system: dysmenorrhea, secondary amenorrhea, breast enlargement, 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: hemodialysis, forced diuresis, maintenance of breathing and cardiovascular system.

Interaction:

Contraindicated combinations:

- mefloquine - the 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, an anticonvulsant 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_1/2up 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 that require 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, and the level of antiepileptic drugs in the blood;

- phenytoin - changes in the concentration of phenytoin in the plasma, phenytoin enhances the hepatic metabolism of valproic acid and reduces its concentration. Clinical observation is recommended, the level of antiepileptic drugs 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 antiepileptic drugs 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 that reduce 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 - an increase in the 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 regardless 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 a picture of peripheral blood, in particular, blood platelets.

Patients who receive al.antiepileptic drugs, transfer to admission 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 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 concentration of attention and speed of psychomotor reactions.

Form release / dosage:Solution for intravenous administration, 100 mg / ml.

Packaging:

To 5 ml of the drug in a colorless glass ampoule (type I), with a red break point and an orange ring at the top; 5 ampoules per transparent plastic tray; 1 pallet together with instructions for use in a cardboard box.

Storage conditions:At a temperature of no higher than 25 ° C, in a place protected from light.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-002567

Date of registration:01.11.2011 / 31.05.2017

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®)