Konvulex tablets, p / o, prolonged action 500mg, No. 50

• 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 seizures in children;

• children's teak;

• treatment and prevention of bipolar disorder, resistant to treatment with lithium or other drugs.

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

Adults are prescribed at an initial dose of 600 mg / day with a gradual increase in the dose by 150-250 mg every 3 days until a clinical effect is achieved (the disappearance of seizures).

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 1000-2000 mg, i.e. 20-25 mg / kg. If necessary, the dose can be increased to a maximum dose of 2500 mg / day (30 mg / kg / day).

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

When carrying out combination therapy, the dose is 10-30 mg / kg / day, followed by an increase of 5-10 mg / kg per week.

For children weighing more than 25 kg, the drug is prescribed at an initial dose of 300 mg / day (5-15 mg / kg / day) with a gradual increase by 5-10 mg / kg per week until a clinical effect (disappearance of seizures) is achieved, while the dose , as a rule, is 1000-1500 mg / day (20-30 mg / kg / day).

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

For children weighing 20-25 kg with monotherapy, the average dose is 15-45 mg / kg / day, the maximum dose is 50 mg / kg / day. With combination therapy - 30-100 mg / kg / day. It should be borne in mind that children weighing less than 20 kg are not recommended to use the drug in the form of prolonged-release tablets, they should be prescribed other forms of the drug.

Although the pharmacokinetics of valproic acid in the elderly may have their own characteristics, this is of limited clinical significance, and the dose should be determined by the clinical effect. Due to a decrease in binding to serum albumin, the proportion of unbound drug in plasma increases. This makes it advisable to carefully select the dose of the drug in the elderly, with the possible use of smaller doses of the drug.

In patients with renal impairment, it may be necessary to reduce the dose of the drug. The dose should be selected according to the monitoring of the clinical condition, since the plasma concentration indicators may be insufficiently informative.

Active ingredient: sodium valproate - 300 mg

Excipients: citric acid - 39 mg, ethyl cellulose - 60 mg, copolymer of methyl methacrylate, trimethylammonioethyl methacrylate chloride and ethyl acrylate (1: 2: 0.1) (eudragit RS30D) - 20.1 mg, talc - 8.1 mg, colloidal silicon dioxide - 6 mg, magnesium stearate - 6 mg.

Shell composition: copolymer of methyl methacrylate, trimethylammonioethyl methacrylate chloride and ethyl acrylate (1: 2: 0.2) (eudragit RL30D type A) - 2.25 mg, copolymer of methyl methacrylate, trimethylammonioethyl methacrylate chloride and ethyl acrylate (1: 2: 0.130) (eudragitol 530) (eudragitol530) (eudragitol) - 0.9 mg, sodium carmellose - 1.27 mg, titanium dioxide - 1.06 mg, talc - 2.02 mg, vanillin - 0.11 mg.

• liver failure;

• acute and chronic hepatitis;

• dysfunction of the pancreas;

• porphyria;

• hemorrhagic diathesis;

• severe thrombocytopenia;

• disorders of urea metabolism (including family history);

• lactation period;

• children weighing less than 20 kg;

• children under 3 years old;

• hypersensitivity to valproic acid and its salts or drug components.

Care should be taken to prescribe the drug to the following categories of patients:

• with anamnestic data on diseases of the liver and pancreas;

• with inhibition of bone marrow hematopoiesis (leukopenia, thrombocytopenia, anemia);

• with renal failure;

• with congenital fermentopathies;

• with organic diseases of the brain;

• with hypoproteinemia;

• during pregnancy (especially the first trimester);

• children with mental retardation.

Description:

Sustained-release tablets, film-coated white, oval, biconvex, with a break line and engraved 'CC5' on one side, with a vanillin smell; at the break - white or almost white.

Composition:

Active ingredient: sodium valproate - 500 mg

Excipients: citric acid - 65 mg, ethyl cellulose - 100 mg, copolymer of methyl methacrylate, trimethylammonioethyl methacrylate chloride and ethyl acrylate (1: 2: 0.1) (eudragit RS30D) - 33.5 mg, talc - 13.5 mg, colloidal silicon dioxide - 10 mg, magnesium stere - 10 mg.

Shell composition: copolymer of methyl methacrylate, trimethylammonioethyl methacrylate chloride and ethyl acrylate (1: 2: 0.2) (Eudragit RL30D type A) - 3.2 mg, copolymer of methyl methacrylate, trimethylammonioethyl methacrylate chloride and ethyl acrylate (1: 2: 0.130) (3.2 mg) eudragit - 1.28 mg, sodium carmellose - 1.8 mg, titanium dioxide - 1.5 mg, talc - 2.87 mg, vanillin - 0.15 mg.

Clinical and pharmacological group: Anticonvulsant drug

Pharmaco-therapeutic group: Antiepileptic drug

pharmachologic effect

Antiepileptic drug. It 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 due to inhibition of the enzyme GABA-transferase. GABA reduces the excitability and seizure readiness of the motor areas of the brain. In addition, the effect of valproic acid on GABAA receptors (activation of GABA-ergic transmission), as well as the effect on voltage-dependent sodium channels, plays a significant role in the mechanism of action of the drug. According to another hypothesis, it acts on the sites of postsynaptic receptors, mimicking or enhancing the inhibitory effect of GABA. A possible direct effect on membrane activity is associated with changes in the conductivity of potassium ions.

Improves the mental state and mood of patients, has antiarrhythmic activity.

Pharmacokinetics

Suction

Valproic acid is almost completely absorbed from the gastrointestinal tract, oral bioavailability is 100%. Food intake does not decrease the rate of absorption. Cmax in blood plasma is reached after 4 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.

Distribution

Css is achieved on days 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%.

Penetrates the BBB. The values ??of the concentration in the cerebrospinal fluid correlate with the value of the non-protein-bound fraction of the active substance. Valproic acid crosses 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.

Withdrawal

Valproic 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 situations

With 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 the age of 18 months, 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 (Vesta, Lennox-Gastaut);

• behavioral disorders due to epilepsy;

• febrile seizures in children;

• children's teak;

• treatment and prevention of bipolar disorder, resistant to treatment with lithium or other drugs.

Dosage regimen

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

Adults are prescribed at an initial dose of 600 mg / day with a gradual increase in the dose by 150-250 mg every 3 days until a clinical effect is achieved (the disappearance of seizures).

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 1000-2000 mg, i.e. 20-25 mg / kg. If necessary, the dose can be increased to a maximum dose of 2500 mg / day (30 mg / kg / day).

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

When carrying out combination therapy, the dose is 10-30 mg / kg / day, followed by an increase of 5-10 mg / kg per week.

For children weighing more than 25 kg, the drug is prescribed at an initial dose of 300 mg / day (5-15 mg / kg / day) with a gradual increase by 5-10 mg / kg per week until a clinical effect (disappearance of seizures) is achieved, while the dose , as a rule, is 1000-1500 mg / day (20-30 mg / kg / day).

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

For children weighing 20-25 kg with monotherapy, the average dose is 15-45 mg / kg / day, the maximum dose is 50 mg / kg / day. With combination therapy - 30-100 mg / kg / day. It should be borne in mind that children weighing less than 20 kg are not recommended to use the drug in the form of prolonged-release tablets, they should be prescribed other forms of the drug.

Although the pharmacokinetics of valproic acid in the elderly may have their own characteristics, this is of limited clinical significance, and the dose should be determined by the clinical effect. Due to a decrease in binding to serum albumin, the proportion of unbound drug in plasma increases. This makes it advisable to carefully select the dose of the drug in the elderly, with the possible use of smaller doses of the drug.

In patients with renal impairment, it may be necessary to reduce the dose of the drug. The dose should be selected according to the monitoring of the clinical condition, since the plasma concentration indicators may be insufficiently informative.

Side effect

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

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

From the nervous system: tremors, changes in behavior, mood or mental state (depression, fatigue, hallucinations, aggressiveness, hyperactivity, psychosis, unusual agitation, restlessness or irritability), ataxia, dizziness, drowsiness, headache, encephalopathy, dysarthria , enuresis, stupor, impaired consciousness, coma.

From the side of the organ of vision: diplopia, nystagmus, flashing 'flies' before the eyes.

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, bruising, hematomas, bleeding).

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

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

From the genitals and mammary gland: dysmenorrhea, secondary amenorrhea, breast enlargement, galactorrhea.

Others: decrease or increase in body weight, peripheral edema, hair loss (as a rule, it recovers after discontinuation of the drug).

Contraindications for use

• liver failure;

• acute and chronic hepatitis;

• dysfunction of the pancreas;

• porphyria;

• hemorrhagic diathesis;

• severe thrombocytopenia;

• disorders of urea metabolism (including family history);

• lactation period;

• children weighing less than 20 kg;

• children under 3 years old;

• hypersensitivity to valproic acid and its salts or drug components.

Care should be taken to prescribe the drug to the following categories of patients:

• with anamnestic data on diseases of the liver and pancreas;

• with inhibition of bone marrow hematopoiesis (leukopenia, thrombocytopenia, anemia);

• with renal failure;

• with congenital fermentopathies;

• with organic diseases of the brain;

• with hypoproteinemia;

• during pregnancy (especially the first trimester);

• children with mental retardation.

Application during pregnancy and lactation

The drug should be prescribed with caution during pregnancy (especially in the first trimester).

The use of the drug during lactation is contraindicated.

Application for violations of liver function

Contraindicated in liver failure, acute and chronic hepatitis.

Application for impaired renal function

The drug should be prescribed with caution in case of renal failure.

Application in children

ѕротивопоказано применение препарата в детском возрасте до 3 лет и у детей с массой тела менее 20 кг.

— осторожностью следует назначать препарат дет¤м с умственной отсталостью.

ѕрименение у пожилых пациентов

” пациентов пожилого возраста следует более тщательно подбирать дозы препарата с возможным применением меньших доз.

ќсобые указани¤

¬о врем¤ лечени¤ целесообразен контроль активности печеночных трансаминаз, концентрации билирубина, картины периферической крови, тромбоцитов крови, состо¤ни¤ системы свертывани¤ крови, активности амилазы (каждые 3 мес¤ца, особенно при комбинации с другими противоэпилептическими средствами).

ѕациентам, которые получают другие противоэпилептические средства, перевод на прием вальпроевой кислотой следует проводить постепенно, достига¤ клинически эффективной дозы через 2 недели, после чего возможна постепенна¤ отмена других противоэпилептических средств. ” пациентов, не получавших лечени¤ другими противоэпилептическими средствами, клинически эффективна¤ доза должна быть достигнута через 1 неделю.

–иск развити¤ побочных эффектов со стороны печени повышен при проведении комбинированной противосудорожной терапии, а также у детей.

Ќе допускаетс¤ прием напитков, содержащих этанол.

ѕеред хирургическим вмешательством необходим общий анализ крови (в т.ч. числа тромбоцитов), определение времени кровотечени¤, показателей коагулограммы.

ѕри возникновении на фоне лечени¤ симптомокомплекса 'острый живот' до начала оперативного вмешательства рекомендуетс¤ определить активность амилазы в крови дл¤ исключени¤ острого панкреатита.

¬о врем¤ лечени¤ следует учитывать возможное искажение результатов анализов мочи при сахарном диабете (вследствие повышени¤ содержани¤ кетоновых тел), показателей функции щитовидной железы.

ѕри развитии любых острых серьезных побочных эффектов пациенту необходимо немедленно обсудить с врачом целесообразность продолжени¤ или прекращени¤ лечени¤.

?л¤ снижени¤ риска развити¤ диспепсических расстройств возможен прием спазмолитиков и обволакивающих средств.

–езкое прекращение приема препарата  онвулексЃ может привести к учащению эпилептических припадков.

¬ли¤ние на способность к вождению автотранспорта и управлению механизмами

¬ период лечени¤ необходимо соблюдать осторожность при вождении транспортных средств и зан¤тии другими потенциально опасными видами де¤тельности, требующими повышенной концентрации внимани¤ и быстроты психомоторных реакций.

ѕередозировка

—имптомы: тошнота, рвота, головокружение, диаре¤, нарушение функции дыхани¤, мышечна¤ гипотони¤, гипорефлекси¤, миоз, кома.

Ћечение: промывание желудка (не позже 10-12 ч) с последующим назначением активированного угл¤, гемодиализ. ‘орсированный диурез, поддержание жизненно важных функций организма.

Ћекарственное взаимодействие

¬альпроева¤ кислота усиливает эффекты, в т.ч. и побочные, других противоэпилептических препаратов (фенитоин, ламотриджин), антидепрессантов, антипсихотических лекарственных средств (нейролептиков), анксиолитиков, барбитуратов, ингибиторов ћјќ, тимолептиков, этанола. ?обавление вальпроевой кислоты к клоназепаму в единичных случа¤х может приводить к усилению выраженности абсансного статуса.

ѕри одновременном применении вальпроевой кислоты с барбитуратами или примидоном отмечаетс¤ повышение концентрации последних в плазме крови.

”величивает T1/2 ламотриджина (ингибирует ферменты печени, вызывает замедление метаболизма ламотриджина, вследствие чего T1/2 его удлин¤етс¤ до 70 ч у взрослых и до 45-55 ч - у детей).

—нижает клиренс зидовудина на 38%, при этом его T1/2 не измен¤етс¤.

“рициклические антидепрессанты, ингибиторы ћјќ, антипсихотические средства (нейролептики) и другие лекарственные средства, снижающие порог судорожной активности, уменьшают эффективность препарата.

ѕри одновременном приеме препарата  онвулексЃ с этанолом и другими лекарственными средствами, угнетающими работу ?Ќ— (трициклические антидепрессанты, ингибиторы ћјќ, антипсихотические лекарственные средства) возможно усиление угнетени¤ ?Ќ—.

ѕри сочетании с салицилатами наблюдаетс¤ усиление эффектов вальпроевой кислоты (вытеснение из св¤зи с белками плазмы).  онвулексЃ усиливает эффект антиагрегантов (ацетилсалицилова¤ кислота) и непр¤мых антикоагул¤нтов.

ѕри сочетании с фенобарбиталом, фенитоином, карбамазепином, мефлохином снижаетс¤ содержание вальпроевой кислоты в сыворотке крови (ускорение метаболизма).

‘елбамат повышает концентрацию вальпроевой кислоты в плазме на 35-50% (необходима коррекци¤ дозы).

ћиелотоксические лекарственные средства - повышение риска угнетени¤ костномозгового кроветворени¤.

¬альпроева¤ кислота не вызывает индукции печеночных ферментов и не снижает эффективности пероральных контрацептивов.

Ётанол и гепатотоксичные лекарственные средства увеличивают веро¤тность развити¤ поражений печени.

¬альпроева¤ кислота может как повышать, так и снижать концентрацию этосуксимида в сыворотке крови вследствие изменени¤ метаболизма.

ћеропенем снижает концентрацию вальпроевой кислоты в плазме, что может привести к снижению противосудорожного эффекта.

ѕри одновременном применении с топираматом повышаетс¤ риск развити¤ гипераммониемии и энцефалопатии.

”слови¤ хранени¤

The drug should be stored out of the reach of children, in a dry place in a tightly closed container at a temperature not exceeding 25 ? C.

Shelf life

The shelf life is 5 years. Do not use after the expiration date.

Terms of sale

The drug is available with a prescription.