DEPAKENE SYRUP 150ML

Antiepileptic agent, has a central muscle relaxant and sedative effect. The mechanism of action is associated with an increase in the content of GABA in the central nervous system (due to inhibition of GABA transferase, as well as a decrease in the reuptake of GABA in brain tissue), resulting in reduced excitability and convulsive readiness of the motor areas of the brain. According to another hypothesis, it acts on sites of postsynaptic receptors, imitating or enhancing the inhibitory effect of GABA. A possible direct effect on membrane activity is associated with changes in the conductivity of potassium. Improves the mental state and mood of patients, has antiarrhythmic activity. It is highly effective in absans and temporal pseudoabsense, few - in psychomotor attacks.

Absorption - high, food slightly reduces the rate of absorption; bioavailability - 100%. TCmax capsules and syrup - 1-4 hours, pills - 3-4 hours, pills with controlled interaction - 2-8 hours, with intravenous administration - by the end of the hourly infusion. Css is achieved on 2-4 days of administration (depending on the intervals between doses). Therapeutic plasma concentrations range from 50-150 mg / l. Pharmacological and therapeutic effects, when used with controlled release forms, do not always depend on plasma concentration. The volume of distribution - 0.2 l / kg. Communication with proteins is 90-95% at plasma concentrations of up to 50 mg / l and decreases to 80-85% at concentrations of 50-100 mg / l (with uremia, hypotroteinemia and cirrhosis, binding to proteins is reduced). It penetrates the placental barrier and the BBB; excreted in breast milk (concentration in breast milk is 1-10% concentration in the mother's blood plasma). The content in the CSF correlates with the value of the fraction not bound to proteins. Metabolized by glucuronization and oxidation in the liver, T1 / 2 - 8-22h. Valproic acid (1-3%) and its metabolites (in the form of conjugates, oxidation products, including ketometabolites) are excreted by the kidneys; small amounts are excreted in faeces and exhaled air. When combined with other drugs, T1 / 2 can be 6-8 hours due to induction of metabolic enzymes, in patients with impaired liver function, elderly patients and children up to 18 months can be significantly longer.The prolonged form is characterized by the absence of latent time of absorption, slow absorption, lower (by 25%), but relatively more stable plasma concentration between 4 and 14 h.

Indications and usage

Epilepsy of various origins, generalized and partial seizures. Epileptic seizures on the background of organic brain diseases. Changes in character and behavior (due to epilepsy). Febrile convulsions (in children), children's tick. Manic-depressive psychosis with a bipolar course, not amenable to treatment with lithium preparations or other drugs. Specific syndromes (Vesta, Lennox-Gasto).

Contraindications

Hypersensitivity, hepatic failure, acute and chronic hepatitis, pancreatic dysfunction, porphyria, hemorrhagic diathesis, severe thrombocytopenia, pregnancy (I term), lactation period, children's age (up to 3 years, except syrup). With care - oppression of bone marrow hematopoiesis (leukopenia, thrombocytopenia, anemia), organic brain disease or liver disease in history; hypoproteinemia, renal failure, pregnancy.

Inside, during a meal or immediately after a meal, without chewing, with a small amount of water, 2-3 times a day. Syrup can be mixed with any liquid or added to a small amount of food. The initial dose for monotherapy for adults and children weighing more than 25 kg is 5-15 mg / kg / day, then this dose is gradually increased by 5-10 mg / kg / week. The maximum dose - 30 mg / kg / day (can be increased with the possibility of organizing control over plasma concentration up to 60 mg / kg / day). When combined therapy in adults - 10-30 mg / kg / day, followed by increasing the dose by 5-10 mg / kg / week. For children with a body weight of less than 25 kg, the average daily dose for monotherapy is 15-45 mg / kg, maximum - 50 mg / kg. Depending on age: newborn - 30 mg / kg, from 3 to 10 years old - 30-40 mg / kg / day, up to 1 year - in 2 doses, in older ones in 3 doses. With combined therapy - 30-100 mg / kg / day. Children with body weight less than 20 kg should not use controlled release tablets. In / in struyno, 400-800 mg or in / in drip, at the rate of 25 mg / kg for 24, 36, 48 hours. When you decide to switch to / in the introduction after oral administration, the first injection is carried out in a dose of 0.5- 1 mg / kg / h 4-6 hours after the last ingestion.

Adverse reactions

From the side of the central nervous system: tremor; rarely - changes in behavior, mood or mental state (depression, fatigue, hallucinations, aggressiveness, hyperactive condition, psychosis, unusual agitation, motor restlessness or irritability), ataxia, dizziness, drowsiness, headache, encephalopathy, dysarthria, enuresis, stupor, disturbance of consciousness, coma. On the part of the senses: diplopia, nystagmus, flickering "flies" before the eyes. On the part of the digestive system: nausea, vomiting, gastralgia, anorexia or increased appetite, diarrhea, hepatitis; rarely - constipation, pancreatitis, up to severe lesions with a fatal outcome (in the first 6 months of treatment, usually for 2-12 weeks). From the side of blood-forming organs and hemostasis system: anemia, leukopenia; thrombocytopenia, decrease in the content of fibrinogen, platelet aggregation and blood clotting, accompanied by prolonged bleeding time, petechial hemorrhages, hemorrhages, hematomas, bleeding, etc. From the metabolic side: decrease or increase in body weight. Allergic reactions: skin rash, urticaria, angioedema, photosensitivity, malignant exudative erythema (Stevens-Johnson syndrome). Laboratory indicators: hypercreatininemia, hyperammonemia, hyperglycemia, hyperbilirubinemia, a slight increase in the activity of “liver” transaminases, LDH (dose-dependent). On the part of the endocrine system: dysmenorrhea, secondary amenorrhea, breast enlargement, galactorrhea. Other: peripheral edema, alopecia. Overdose. Symptoms: nausea, vomiting, dizziness, diarrhea, respiratory dysfunction, muscular hypotonia, hyporeflexia, miosis, coma (on EEG an increase in slow waves and background activity). Treatment: gastric lavage (no later than 10-12 hours), taking activated charcoal, forced diuresis, maintaining vital functions, hemodialysis.

Special notes

During treatment, it is necessary to monitor the activity of liver transaminases, bilirubin, a picture of peripheral blood, blood platelets, the state of the blood coagulation system, amylase (every 3 months, especially possible combination with other antiepileptic drugs. Patients who receive otherAntiepileptic drugs, transfer to the reception of valproic acid should be carried out gradually, reaching a clinically effective dose after 2 weeks. Then carry out the gradual abolition of other antiepileptic drugs. In patients not treated with other antiepileptic drugs, a clinically effective dose should be achieved after 1 week. It should be borne in mind that the risk of side effects from the liver is increased during the combined anticonvulsant therapy. Children have an increased risk of severe or life-threatening hepatotoxic effects (especially up to 2 years). Use during pregnancy is not recommended. It should be borne in mind that valproic acid can cause various congenital anomalies, especially spina bifida. Women of reproductive age are recommended to use reliable methods of contraception during treatment. During the period of treatment, it is necessary to refrain from engaging in potentially hazardous activities that require increased concentration of attention and quickness of psychomotor reactions. It is not allowed to accept beverages containing ethanol. Before surgery, a complete blood count is necessary (including platelet counts), bleeding time, and coagulogram values. If symptoms of an "acute" abdomen occur during treatment, it is recommended to determine the level of amylase in the blood prior to the start of surgical intervention in order to rule out acute pancreatitis. During treatment, consideration should be given to the possible distortion of the results of urine tests for diabetes mellitus (due to an increase in ketoproducts), indicators of thyroid function. With the development of spontaneous hematomas and bleeding and the occurrence of symptoms such as severe weakness, lethargy, swelling, vomiting and jaundice, you should immediately stop using the drug. Dyspeptic disorders develop less frequently on the background of antispasmodics and coating agents.

With the simultaneous appointment of valproic acid with ethanol and other drugs that inhibit the central nervous system, may increase the depression of the central nervous system; with barbiturates or primidone - increasing their concentration in the blood plasma; with salicylates - enhancing the effects of valproic acid (displacement from association with plasma proteins).When combined with phenobarbital, phenytoin (and, possibly, other antiepileptic drugs - derivatives of hydantoin), Carbamazepine , mefloquine decreases the content of valproic acid in serum (accelerated metabolism). Combination with anticoagulants (coumarin and indanedione derivatives), Heparin , thrombolytic agents and antiplatelet agents (ASK derivatives and other platelet aggregation inhibitors) increases the risk of bleeding. While the use of valproic acid, in addition to increased CNS depression, the following drugs can lower the threshold for seizure activity: tricyclic antidepressants, bupropion, clozapine, Haloperidol , loxapine, maprotiline, molindone, MAO inhibitors , the phenothiazines, pimozide, thioxanthenes. Simultaneous use of tricyclic antidepressants (imipramine) or phenytoin can cause generalized epileptic seizures, clonazepam - absans. Ethanol and other hepatotoxic drugs increase the likelihood of liver damage. Enhances effects, incl. side, other antiepileptic drugs (phenytoin, lamotrigine), antidepressants, neuroleptics, tranquilizers, barbiturates, MAO inhibitors, timoleptic, ethanol. Valproic acid does not induce hepatic enzymes and does not reduce the effectiveness of oral contraceptives. Felbamate increases the concentration of valproic acid in plasma by 35-50% (dose adjustment is necessary). Increases T1 / 2 lamotrigine (inhibits liver enzymes, causes a slowdown in lamotrigine metabolism, as a result of which T1 / 2 extends it to 70 h in adults and to 45-55 h in children). Reduces clearance of zidovudine by 38%, while T1 / 2 does not change.