Convulex coated pills prolonged 500mg N50
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Active ingredients
Valproic acid
Release form
Pills
Composition
Sodium valproate 500 mg Auxiliary substances: 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, silicon colloidal iodragitol RS30D) - 33.5 mg, talc - 13.5 mg, silicon colloidal iodragitol RS30D) - 33.5 mg, talc - 13.5 mg, silicon colloidal iodine without hydrochloride RS30D) - 33.5 mg, 13.5 mg, talc - 13.5 mg, 33.5 mg without acyl acetate, 30.5 mg; , magnesium stearate - 10 mg. Shell composition: methyl methacrylate, trimethylammonioethylmethacrylate chloride and ethyl acrylate copolymer (1: 2: 0.2) (Eudragit RL30D type A) - 3.2 mg, methyl methacrylate copolymer, trimethylammonioethyl methacrylate chloride and ethyl acrylate / acrylate), and a methyl acrylate copolymer, methyl acrylate, trimethylammonioethyl methacrylate chloride and ethyl acrylate / ethyl acrylate / ethyl acrylate / ethyl acrylate / ethyl acrylate / methyl acrylate, trimethylammonioethyl methacrylate chloride and ethyl acrylate acrylate / methyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate, ethyl acrylate and ethyl acrylate. RS30D) - 3.2 mg, triethyl citrate - 1.28 mg, karma sodium ellose - 1.8 mg, titanium dioxide - 1.5 mg, talc - 2.87 mg, vanillin - 0.15 mg.
Pharmacological effect
Antiepileptic drug. It also has a central muscle relaxant and sedative effect. The mechanism of action is mainly due to an increase in the content of GABA in the central nervous system due to inhibition of the enzyme GABA-transferase. GABA reduces the excitability and convulsive readiness of the motor areas of the brain. In addition, an important role in the mechanism of action of the drug belongs to the effects of valproic acid on GABAA receptors (activation of GABA-ergic transmission), as well as the effect on potential-dependent sodium channels. According to another hypothesis, it acts on sites of postsynaptic receptors, imitating or strengthening the inhibitory effect of GABA. A possible direct influence on the activity of membranes is associated with changes in conductivity for potassium ions. Improves the mental state and mood of patients, has antiarrhythmic activity.
Pharmacokinetics
Absorption Valproic acid is almost completely absorbed from the gastrointestinal tract, bioavailability when administered orally is 100%. Meal does not reduce the rate of absorption. Cmax in the blood plasma after taking the pills of prolonged action is reached after 4 hours, Cmax in the blood plasma after taking the drops for oral administration - after 1-3 hours. The therapeutic concentration of valproic acid in the blood plasma is 50-150 mg / l. The prolonged form is characterized by a slow absorption, lower (by 25%), but more stable plasma concentration between 4 and 14 hours. The distribution of Css is achieved by 2-4 days of treatment, depending on the intervals between doses of doses. At plasma concentrations up to 50 mg / l binding valproic acid Ooty with plasma proteins is 90-95%,at a concentration of 50-100 mg / l - 80-85%. The concentration values in the cerebrospinal fluid correlate with the value of the non-protein fraction of the active substance. Valproic acid penetrates the placental barrier, excreted in breast milk. Concentration in breast milk is 1-10% concentration in the mother's plasma. Metabolism T1 / 2 of valproic acid in monotherapy and in healthy volunteers is 8-20 hours. Pharmacokinetics in special clinical situations. In uremia, hypoproteinemia and cirrhosis, the binding of valproic acid to plasma proteins is reduced. When combined with other drugs, T1 / 2 can be 6-8 h. 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, absansy, myoclonic, atonic); partial epileptic seizures in adults and children (with or without secondary generalization); specific syndromes (Vesta, Lennox-Gasto); behavioral disorders due to epilepsy; febrile seizures in children, children's tic; treatment and prevention of bipolar affective disorders (for drops for (inside), treatment and prevention of bipolar affective disorders that are resistant to treatment with lithium preparations or other drugs (for long-acting pills).
Contraindications
Hepatic insufficiency, acute and chronic hepatitis, pancreatic dysfunction, porphyria, hemorrhagic diathesis, severe thrombocytopenia, urea metabolism (including in the family history), combination with meflokhin, St. John's wort, and lamotrigine; lactation period body less than 7.5 kg (for oral drops); children weighing less than 20 kg (for long-acting pills); children up to 3 years old (for long-acting pills); hypersensitivity to valproic acid e and its salts or components of the drug. With caution: with anamnestic data on diseases of the liver and pancreas (includingfamily history); in the suppression of bone marrow hematopoiesis (leukopenia, thrombocytopenia, anemia); in renal failure; in congenital fermentatives; in organic brain diseases; in hypoproteinemia; in pregnancy (especially in the first trimester); in children with mental retardation, in children with mass body more than 7.5 kg (for drops for ingestion).
Precautionary measures
Application for violations of the liver, contraindicated in severe violations of the liver. With extreme caution, the drug should be prescribed for indications of a history of liver disease. Use for impaired renal functionPatients with renal insufficiency may require a reduction in the dose of the drug. Dose set monitoring the clinical condition of the patient, because plasma valproic acid concentrations may not be sufficiently informative. Use in children Contraindications: children under 3 years of age (for pills with prolonged action).
Use during pregnancy and lactation
During treatment should be protected from pregnancy. In animal experiments, the teratogenic effect of valproic acid was revealed. The incidence of neural tube defects in children born to women who took valproate in the first trimester of pregnancy is 1-2%. It is advisable in this regard, the use of drugs of folic acid. In the first trimester of pregnancy, you should not start treatment with Konvulex. If the pregnant woman is already receiving the drug, then due to the risk of increased seizures, treatment should not be interrupted. The drug should be used in the smallest effective doses, avoiding combination with other anticonvulsants and, if possible, regularly controlling the concentration of valproic acid in the plasma.
Dosage and administration
Drops for ingestion are taken orally 2-3 times / day, regardless of the meal, with a small amount of water. Adults are prescribed in the initial dose of 600 mg / day with a gradual increase every 3 days until a clinical effect is achieved (disappearance of seizures). The initial dose at 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 1-2 g, i.e. 20-30 mg / kg.If necessary, the dose can be increased to 2.5 g / day (30 mg / kg / day). The maximum dose is 30 mg / kg / day (in patients with accelerated valproic acid metabolism, the maximum dose can be increased to 60 mg / kg / day under control of the concentration of valproic acid in the blood plasma). When combined therapy is administered, the dose is 10-30 mg / kg / day, followed by an increase of 5-10 mg / kg per week. Children over 25 kg are prescribed in the initial dose of 300 mg / day (5-15 mg / kg / day), with a gradual increase of 5-10 mg / kg per week until reaching the clinic of its effect (the disappearance of seizures), while the dose is usually 1–1.5 g / day (20–30 mg / kg / day). The maximum dose is 30 mg / kg / day (for patients with accelerated valproic acid metabolism, the maximum the dose can be increased up to 60 mg / kg / day under the control of plasma valproic acid concentration). For children with a body weight of 7.5-25 kg with monotherapy, the average dose is 15-45 mg / kg / day, the maximum dose is 50 mg / kg per day With combined 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 pills with prolonged action, they should use other forms of the drug.
Side effects
In general, Convulex well tolerated by patients. Side effects are possible mainly with plasma concentrations above 100 mg / l or with combination therapy. On the digestive system: nausea, vomiting, gastralgia, decreased or increased appetite, diarrhea, hepatitis, constipation, pancreatitis, up to severe lesions with lethal outcome (in the first 6 months of treatment, more often for 2-12 weeks). From the CNS: tremor, diplopia, nystagmus, flies before the eyes, changes in behavior, mood or mental state (depression, feeling tired, hallucinations, aggressiveness, hyperactivecondition, psychosis, unusual agitation, restlessness or irritability), ataxia, dizziness, drowsiness, headache, encephalopathy, dysarthria, enuresis, stupor, impaired consciousness, coma. On the hemopoietic system: anemia, leukopenia, thrombocytopenia, decrease in fibrinogen content and platelet aggregation, leading to the development of hypocoagulation (accompanied by prolonged bleeding time, petechial hemorrhages, hemorrhages, hematomas, bleeding). On the metabolic side: decrease tion or increase in mass tela.So endocrine system: dysmenorrhea,secondary amenorrhea, an increase in the mammary glands, galactorrhea. From the laboratory indicators: hypercreatininemia, hyperammonemia, hyperbilirubinemia, a slight increase in liver transaminase activity, LDH (dose-dependent). Allergic reactions: skin rash, urticaria, angioproedema, allygic reactions: skin rashes, nettle rash, angiouro-nephrotic pancreatitis, LDH (dose-dependent). - Johnson). Other: peripheral edema, hair loss (usually restored after discontinuation of the drug).
Overdose
Symptoms: nausea, vomiting, dizziness, diarrhea, respiratory dysfunction, muscular hypotonia, hyporeflexia, miosis, coma. Treatment: gastric lavage (no later than 10-12 h) with subsequent administration of activated carbon, hemodialysis. Forced diuresis, maintaining vital body functions.
Interaction with other drugs
Contraindicated combinations Meflokhin: the risk of epileptic seizures due to increased metabolism of valproic acid and a decrease in its concentration in plasma and, on the other hand, the convulsive effect of meflokhin. necrolysis). Valproic acid inhibits liver microsomal enzymes, providing lamotrigine metabolism, which slows down its T1 / 2 up to 70 hours in adults and up to 45-55 hours in children and increases plasma concentration. If the combination is necessary, careful clinical and laboratory monitoring is required. Combinations requiring special precautions Carbamazepine: valproic acid increases the plasma concentration of the active metabolite of carbamazepine to an overdose. In addition, carbamazepine increases hepatic metabolism of valproic acid and reduces its concentration. These circumstances require the physician's attention and determination of plasma concentrations and possible revision of their doses. Phenobarbital, primidone: valproic acid increases the concentration of phenobarbital or primidone in the plasma to overdose, more often in children. In turn, phenobarbital or primidone increase the hepatic metabolism of valproic acid and reduces its concentration.Clinical observation is recommended during the first 2 weeks of combined treatment with an immediate reduction of the dose of phenobarbital or primidone when signs of sedation appear, determination of the level of anticonvulsants in the blood. Clinical observation, determination of the level of anticonvulsants in the blood, and changes in dosage if necessary are recommended. Clonazepam: adding valproic acid to clonazepam in isolated cases can lead to increased severity of absanous serum serum. Ethosuximide: valproic acid can both increase and decrease the concentration of ethosuximide in serum serum levels. changes in its metabolism. Recommended clinical observation, determination of the level of anticonvulsants in the blood, changing the dosage if necessary. Topiramat: increases the risk of developing hyperammonemia and encephalopathy. Felbamate: an increase in the concentration of valproic acid in plasma by 35-50%, with an overdose risk. Clinical observation, determination of the level of valproic acid in the blood, changing the dosage of valproic acid when combined with felbamate and after its withdrawal are recommended. In turn, valproic acid potentiates the action of these psychotropic drugs, as well as benzodiazepines. Tsimetidin, erythromycin: inhibit the hepatic metabolism of valproic acid and increase its concentration in plasma. Zidovudine: valproic acid increases the concentration of zidovudine in the plasma, which leads to an increase in its toxicity. , monobactam: meropenem, panipenem, as well as aztreonam and imipenem reduce the concentration of valproic acid in the plasma, which may lead to a decrease in the anticonvulsant effect. torye should take into vnimanieAtsetilsalitsilovaya acid: amplification of valproic acid due to the displacement effects of its association 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 necessary when co-administered with vitamin K-dependent anticoagulants. Valproic acid. Miotoxic drugs: increased risk of inhibition of bone marrow hematopoiesis. Ethanol and hepatotoxic drugs: increase the likelihood of liver damage. Other combinations Oral contraceptives: Valproic acid does not induce 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 liver failure and pancreatitis when using valproic acid preparations, the following should be kept in mind: - high-risk groups are infants and children under 3 years old, with severe epilepsy, often associated with brain damage and congenital or degenerative diseases; - in most cases, abnormal liver function developed in the first 6 months (usually between 2 and 12 weeks) of treatment, more often with a combined antiepilepte 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 patient’s age; liver failure during pancreatitis increases the risk of death; identifying early symptoms such as asthenia, anorexia, extreme fatigue, drowsiness, sometimes accompanied by vomiting and abdominal pain; however, there may be a recurrence of epileptic seizures against the background of unchanged antiepileptic therapy. In such cases, you should immediately consult a doctor for a clinical examination and analysis of liver function. prothrombin levelfibrinogen, 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 other antiepileptic drugs should be transferred to receive valproic acid carry out gradually, reaching a clinically effective dose after 2 weeks, after which other antiepileptic drugs can be gradually canceled. In patients who have not received treatment with other antiepileptic drugs, a clinically effective dose should be achieved after 1 week. The risk of side effects from the liver is increased during combination anti-convulsant therapy, as well as in children. Drinking ethanol-containing beverages is not allowed. Before surgery, a complete blood test (including platelet count), determination of bleeding time, coagulogram indicators are necessary. If acute stomach symptoms develop during treatment, it is recommended to determine amylase activity in the blood to exclude acute pancreatitis. During treatment, possible distortion of urine test results in diabetes mellitus (due to an increase in the content of ketone ), in the development of any acute serious side effects, you should immediately discuss with your doctor the appropriateness of continuing or stopping the treatment. In order to reduce the risk of dyspeptic symptoms, you can receive antispasmodics and enveloping drugs. on the ability to drive vehicles and control mechanisms. During the period of treatment, care must be taken when driving E tools and other lesson potentially dangerous activities which require high concentration and psychomotor speed reactions.