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

Excipients: maltitol liquidand80/55) 0.8 g, methyl parahydroxybenzoate 1.0 mg, propyl parahydroxybenzoate 0.4 mg, sodium saccharint 1.0 mg, sodium cyclamate 3.0 mg, sodium chloride 0.4 mg, raspberry flavor 9/372710 0.4 mg, peach flavoring 9/030307 1,25 mg, water purified to 1,0 ml.

Description:Colorless or slightly yellowish syrup with a fruity smell.

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, in the mechanism of action of the drug, an important role is played by the action of valproic acid on GABA receptors_A(the 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. A possible direct effect 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 concentration in the plasma is noted 1-3 hours after the administration of the syrup. The equilibrium concentration is achieved on the 2nd-4th day of treatment, depending on the intervals between doses. Therapeutic concentrationValproic acid in the blood plasma varies between 50-150 mg / l. The connection with plasma proteins is 90-95% at a plasma concentration of up 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 of the valproic acid fraction unrelated to plasma proteins.

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 10 to 15 hours, in children 6-10 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 children under 18 months can be significantly longer.

Indications:

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

- generalized epileptic seizures in children: clonic, tonic, tonic-clonic, atonicoeskoe, myoclonic, absences;

- Vest syndrome, Lennox-Gastaut syndrome;

- partial epileptic seizures in children: with secondary generalization or without it.

- febrile convulsions in children, children's teak.

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 (below 75 x 10⁹/ l);

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

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

lactation period.

Carefully:

The purpose of CONVULEX® to the following categories of patients:

- 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.According to available data in humans valproic acid mainly causes disruption of the development of the neural tube: myelomeningocele, spina bifida (1-2%). Cases of facial dysmorphia and developmental defects of limbs (especially their shortening) are described, as well as the developmental defects of the cardiovascular system. The risk of malformations is higher with combined therapy than with monotherapy with sodium valproate.

Given the above, the use of the drug in pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus. In the first trimester of pregnancy should not begin treatment with the drug KONVULEKS ®. If treatment with valproic acid in a pregnant woman is already effective, interrupt treatment should not be. In such cases, monotherapy is recommended, and the minimum effective daily dose should be divided into two doses. In addition to anti-epileptic therapy, folic acid preparations (at a dose of 5 mg per day) can be added to minimize the risk of developing neural tube defects.

Valproic acid can cause hemorrhagic syndrome in newborns, which, apparently, is associated with hypofibrinogenemia. There have been cases of development of fetal affinity with lethal outcome.Perhaps this is due to a decrease in a number of clotting factors.

In newborns, the number of platelets, the level of fibrinogen in the plasma, and the coagulation factors must be determined.

Because the valproic acid is excreted in breast milk in concentrations from 1% to 10%, it is recommended to stop breastfeeding while taking prep.

Dosing and Administration:

CONVULX ® is taken orally, regardless of intake, food, with a small amount of liquid.

The dosage regimen is selected individually, taking into account the age and body weight of the patient.

The initial daily dose for children weighing less than 20 kg at all recommended conditions is 10-15 mg / kg / day, with a gradual increase in the dose (by 5-10 mg / kg / week) to achieve the optimal clinical effect (the disappearance of convulsive seizures).

For children weighing more than 20 kg at all recommended conditions, the initial daily dose is 300 mg, with a gradual increase in the dose (by 5-10 mg / kg / week) to achieve the optimal clinical effect.

The average daily dose of 30 mg / kg can be increased under the control of concentration of the drug in the blood plasma to 40-60 mg / kg.

Average daily intake for children with monotherapy - 30 mg / kg, for teenagers - 20-30 mg / kg. The daily dose is recommended to be divided into two reception for patients under the age of 1 year, for three admission patients aged over 1 year.

Patients with renal insufficiency. It may be necessary to reduce the dose of the drug. The dose should be selected according to 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 with the concentration of valproic acid in plasma above 100 mg / l or with combination therapy.

From the central nervous system: ataxia, cases of cognitive impairment with progression up to the development of a complete picture of dementia syndrome (reversible within a few weeks or months after discontinuation of the drug), confusion or convulsions, stupor and lethargy, sometimes resulting in transient coma (encephalopathy), reversible parkinsonism, headache pain, dizziness, mild postural tremor and drowsiness, changes in behavior, mood or mental state (depression, fatigue, hallucinations, aggressiveness,hyperactive state, psychosis, unusual agitation, motor anxiety or irritability), dysarthria.

From the gastrointestinal tract: nausea, vomiting, gastralgia, decreased or increased appetite, constipation, diarrhea (which usually occur for several days without drug discontinuation), liver dysfunction, hepatitis, pancreatitis up to severe lesions with lethal outcome (in the first 6 months of treatment, more often for 2-12 weeks).

On the part of the organs of hematopoiesis and the system of hemostasis: depression of bone marrow hematopoiesis (anemia, leukopenia or pancytopenia) thrombocytopenia, reduction of fibrinogen and platelet aggregation, leading to the development of hypocoagulation (accompanied by lengthening of time, bleeding, petechial hemorrhages, bruises, bruises, bleeding).

From the side of the urinary system: enuresis, cases of reversible Fanconi syndrome (unclear genesis).

From the endocrine system: disorders of the menstrual cycle, secondary amenorrhea, enlargement of the mammary glands, galactorrhea.

Allergic reactions: skin rash, hives, vasculitis, angioedema, photosensitization, cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme.

Laboratory indicators: isolated and moderate hyperammonaemia unchanged in the assays of the liver, especially in polytherapy (discontinuation of the drug is not needed), it is possible hyperammonemia associated with neurological symptoms (requires further inspection), possibly increased activity "liver" enzymes, reducing fibrinogen or increased bleeding time, usually without clinical manifestations and especially at high doses (valproic acid has an inhibitory effect on platelet aggregation second step), hyponatremia.

Other: teratogenic risk (see. section "Pregnancy and lactation"), diplopia, nystagmus, flashing "flies" before the eyes, reversible or irreversible hearing loss, peripheral edema, weight gain, disorders of the immune system, hair loss (as a rule, it is restored after drug discontinuation).

Overdose:

Symptoms: nausea, vomiting, dizziness, diarrhea, impaired respiratory function, muscle hypotonia, hyporeflexia, miosis, coma with muscular hypotonia, hyporeflexia, miosis, respiratory depression, metabolic acidosis, described cases of intracranial hypertension related to cerebral edema.

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

Interaction:

Contraindications:

- 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, due to the convulsive 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 concentration of drugs in the plasma and the possible revision of their doses;

- phenobarbital, primidone - valproic acid increases the concentration of phenobarbital and primidone in plasma to signs of overdose, more often in children. In its turn, phenobarbital and primidon increase the hepatic metabolism of valproic acid and reduce its concentration. Clinical observation during the first 2 weeks of combined treatment with immediate reduction of the dose of phenobarbital and primidone is recommended in case of signs of sedation, the concentration of antiepileptic agents 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, the determination of the concentration of antiepileptic agents in the blood, the change in dosage, 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, the determination of the concentration of antiepileptic agents in the blood, the change in dosage, if necessary;

- topiramate - the risk of developing hyperammonemia or encephalopathy increases. Clinical and laboratory monitoring is recommended during the first month of treatment and in case of symptoms of hyperammonemia;

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

- neuroleptics, monoamine oxidase inhibitors (MAO), 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; Clinical monitoring and, if necessary, adjustment of the dose of the drug are recommended.

- 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, and aztreonam and imipenem reduce the concentration of valproic acid in the plasma, which can lead to a decrease in anticonvulsant effect. It is recommended clinical observation, determination of the concentration of drugs in the blood plasma, it may be necessary to adjust the dose of valproic acid during treatment with an antibacterial agent and after its withdrawal.

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, valproic acid;

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

- ethanol and hepatotoxic drugs - increase probability of 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:

There is evidence of the possible appearance of suicidal thoughts and behavior in patients receiving antiepileptic drugs. A meta-analysis of clinical trials of antiepileptic drugs revealed a slightly increased risk of suicidal thoughts and behavior. The mechanism of this phenomenon is not fully understood, the possibility of increasing the risk of suicidal thoughts and behavior when using valproic acid drugs is not ruled out. Patients, their families, as well as medical workers who provide assistance to such a patient, should be informed of the risk of suicidal thoughts and behavior.

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:

- High-risk groups 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 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 during the first 6 months, it is necessary to periodically check the function of the liver - Activity "liver" enzymes, prothrombin content, fibrinogen, clotting factors, bilirubin, and amylase (every 3 months, especially in combination with other antiepileptic means) and a picture of peripheral blood, in particular blood platelets. The development of severe thrombocytopenia (below 75 x 10⁹/ L) in the treatment with high doses of valproic acid (with plasma levels above 110 mg / l for women and 135 mg / l for men). The number of platelets was normalized when treatment was withdrawn, in some patients it was normalized and without treatment cancellation.

When treating hypothermia valproic acid can occur - in combination with hyperammonemia, and without it. Hypothermia can be accompanied by lethargy, confusion, coma, impaired cardiovascular activity and respiration.

When using valproic acid, even with normal liver function, hyperamonia can be observed.It is necessary to determine the level of ammonium in the blood when patients develop drowsiness, vomiting, mental changes, and hypothermia. If there is severe hyperammonemia, treatment with valproic acid should be discontinued. Giperammoniemicheskaya encephalopathy (in some cases, fatal) upon application of valproic acid can develop in patients with disorders of urea metabolism, in particular deficient ornitintranskarbamilazy. Prior to treatment with valproic acid must examine the status of urea metabolism in patients with a history of encephalopathy and coma of unknown origin, with periodic vomiting and lethargy, irritability episodes, ataxia, presence of disorders of urea metabolism in the family history. Patients with hyperammonemic encephalopathy who developed with valproic acid therapy should receive appropriate treatment immediately, including the abolition of valproic acid.

Patients who receive other antiepileptics transfer to receiving valproate should be carried out gradually, reaching a clinically effective dose after 2 weeks, after which the possible phasing out the other antiepileptic agents.In patients who have not been 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.

When using the drug in patients with renal insufficiency, it is recommended to take into account the increased concentration of free form of valproic acid in the blood plasma and reduce the dose.

If it is necessary to prescribe the drug to patients with systemic lupus erythematosus and other diseases of the immune system, the expected therapeutic effect and the possible risk of therapy should be evaluated, since when the drug was used in extremely rare cases, violations from the immune system were noted.

It is not recommended to prescribe the drug to patients with a deficiency of urea enzymes. These patients described several cases of hyperammonemia, accompanied by a stupor and / or coma.

During the treatment, it is not allowed to take drinks containing ethanol.

Patients should be warned about the risk of weight gain at the beginning of treatment and recommend compliance with the diet to minimize such effects.

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

A sharp discontinuation of the drug CONVULEX® may 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:

Syrup for children, 50 mg / ml.

Packaging:

To 100 ml in a bottle of brown glass, with a screwed metal lid with the control of the first autopsy.

For 1 bottle together with a dimensional plastic syringe and instructions for use in a cardboard pack.

Storage conditions:

In the dark place 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 N011170 / 01

Date of registration:12.05.2010 / 06.06.2017

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®)