Enkorat tablets 300mg, No. 100

• epilepsy - minor seizures (absences, difficult absences);

• large seizures;

• focal seizures.

Inside during meals, the dose is set individually. The tablet should be swallowed whole without breaking or chewing. You cannot change the dose and treatment regimen without consulting your doctor.

Adults: the drug is prescribed in an initial daily dose of 0.3-0.6 g in 2 divided doses. The dose is gradually increased by 0.1-1.15 g / day every 3-4 days until the desired effect is achieved. The maximum daily dose is 2.4 g.

Children weighing less than 40 kg: the drug is prescribed in a daily dose of 20 mg / kg.

Children weighing 40 kg or more: the maximum daily dose is 40 mg / kg of body weight. Multiplicity of appointment - 2 times / day.

Cancellation of treatment is carried out with a gradual dose reduction, over a period of 1-2 years. If therapy is effective, the dose may not be recalculated depending on the child's body weight if there is no deterioration in the ECG.

Enteric-coated tablets

1 tab.

sodium valproate

Excipients: colloidal silicon dioxide, microcrystalline cellulose, corn starch, polyvinylpyrrolidone K30, calcium silicate, magnesium stearate, purified talc, sodium starch glycolate (type A), hypromellose 2910, dibutyl phthalate, methacrylic acid dioxide copolymer, methacrylic acid dioxide type) crimson 4R lacquer, dye Sunset Yellow FCF lacquer.

• severe dysfunction of the liver and / or pancreas;

• porphyria;

• hemorrhagic diathesis;

• severe thrombocytopenia;

• leukopenia;

• children under 3 years old;

• pregnancy;

• lactation period;

• hypersensitivity to the drug.

With caution, patients with anamnestic data on liver and pancreas diseases, as well as damage to the bone marrow; impaired renal function; congenital enzymopathies; mentally retarded children; organic brain lesions, hyioprotenemia.

pharmachologic effect

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 the brain), as a result of which the excitability and convulsive readiness of the motor zones of the brain decrease. 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 potassium conductance. Improves the mental state and mood of patients, has antiarrhythmic activity.

Pharmacokinetics

When administered orally, it is well absorbed in the gastrointestinal tract. Bioavailability is about 100%. Cmax in blood plasma is reached 3-4 hours after administration. Css is achieved on 2-4 days of admission (depends on the intervals between doses). Therapeutic plasma concentrations range from 50-150 mg / l. Plasma protein binding - 90%. Penetrates the placental and blood-brain barriers; excreted in breast milk (the concentration in breast milk is 1-10% of the concentration in the mother's blood plasma). The content in the cerebrospinal fluid correlates with the size of the non-protein-bound fraction.

T1 / 2 varies from 6 to 16 hours. It is metabolized in the liver with the formation of glucuronide. It is excreted mainly by the kidneys as a metabolite; small amounts of the drug are excreted in the feces and exhaled air.

Side effect

On the part of the digestive system: at the beginning of treatment, transient disorders are possible: anorexia, stomach pain, nausea, vomiting, diarrhea, increased appetite; rarely - constipation, pancreatitis up to severe damage with a fatal outcome.

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

From the senses: diplopia, nystagmus, flashing of flies before the eyes.

From the liver: a transient increase in the activity of hepatic enzymes is possible, which is observed during the first few months of treatment and often does not manifest any clinical symptoms (frequency is about 40%). The risk of developing these side effects depends on the dose of the drug; when the dose is reduced, these effects diminish or disappear. The development of fulminant hepatitis with a fatal outcome is very rarely observed, and it is far from always possible to identify previous changes in liver function indicators.

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

From the endocrine system: dysmenorrhea, secondary amenorrhea, breast enlargement, galactorrhea.

From the side of hematopoietic organs: anemia, thrombocytopenia, leukopenia, decreased fibrinogen content, platelet aggregation and blood clotting, accompanied by prolonged bleeding time, petechial hemorrhages, bruising, hematomas, bleeding.

From the side of metabolism: decrease or increase in body weight.

Laboratory indicators: hypercreatininemia, hyperbilirubinemia, hyperammonemia.

Others: peripheral edema.

Application during pregnancy and lactation

Contraindicated during pregnancy and lactation.

Application for violations of liver function

Contraindicated:

• severe liver dysfunction.

Application for impaired renal function

With caution in case of impaired renal function.

Application in children

Children weighing less than 40 kg: the drug is prescribed in a daily dose of 20 mg / kg.

Children weighing 40 kg or more: the maximum daily dose is 40 mg / kg of body weight. Multiplicity of appointment - 2 times / day.

Cancellation of treatment is carried out with a gradual dose reduction, over a period of 1-2 years. If therapy is effective, the dose may not be recalculated depending on the child's body weight if there is no deterioration in the ECG.

Contraindicated in children under 3 years of age.

special instructions

Before starting treatment and during treatment, it is recommended to monitor the functional state of the liver and pancreas, the picture of peripheral blood, blood coagulation indicators. If there is or suspicion of liver and pancreatic dysfunction, as well as blood clotting disorders, the drug should be discontinued.

When combined therapy with other anticonvulsants and drugs, it is advisable to control, especially at the beginning of treatment, the plasma concentration of another drug, since it can change under the influence of Encorat.

For patients receiving other antiepileptic drugs, transfer to 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 have not received treatment 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 with combined anticonvulsant therapy, as well as in children.

Consideration should be given to the increased risk of bleeding in patients receiving anticoagulant or thrombolytic therapy.

Against the background of treatment with Enkorat, a false-positive reaction of urine to ketone bodies is possible.

There are reports of changes in the functional state of the thyroid gland during therapy with Enkorat.

Before surgery, a general blood test (including the number of platelets), determination of bleeding time, and coagulogram indicators are required.

If symptoms of an acute abdomen occur during treatment, it is recommended to determine the level of amylase in the blood before the start of surgery to exclude acute pancreatitis.

During treatment, one should take into account the possible distortion of the results of urine tests in diabetes mellitus (due to an increase in the content of keto products), indicators of thyroid function.

If any acute, serious side effect develops, you should immediately discuss with your doctor whether to continue or discontinue treatment.

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

Influence on the ability to drive vehicles and use mechanisms

When using the drug, one should refrain from potentially hazardous activities that require increased attention, quick mental and motor reactions.

Overdose

Symptoms: increased severity of side effects - nausea, vomiting, dizziness, diarrhea, respiratory failure, muscle hypotension, hyporeflexia, miosis, coma.

Treatment: gastric lavage, maintaining adequate diuresis, hemodialysis and hemoperfusion, symptomatic therapy.

Drug interactions

Valproic acid enhances the effects, incl. side, other antiepileptic drugs (phenytoin, lamotrigine), anxiolytic drugs (tranquilizers), MAO inhibitors, thymoleptics, ethanol.

The addition of valproate to clonazepam in isolated cases can lead to an increase in the severity of the absence status.

With the simultaneous use of valproic acid with barbiturates or irimidone, an increase in their concentration in blood plasma is noted.

Increases the T1 / 2 of lamotrigine (inhibits liver enzymes, slows down the metabolism of lamotrigine, as a result of which its T1 / 2 lengthens to 70 hours in adults and to 45-55 hours in children).

Reduces the clearance of zidovudine by 38%, while its T1 / 2 does not change.

Tricyclic antidepressants, MAO inhibitors, antipsychotics (neuroleptics), drugs that lower the threshold of seizure activity, reduce the effectiveness of valproic acid.

When combined with salicylates, there is an increase in the effects of valproic acid (displacement from the connection with plasma proteins).

Strengthens the effect of antiplatelet agents (acetylsalicylic acid) and indirect anticoagulants.

When combined with phenytoin, mefloquine, the content of valproic acid in the blood serum decreases (acceleration of metabolism).

Felbamate increases the concentration of valproic acid in plasma by 35-50% (dose adjustment is necessary).

With the simultaneous use of valproic acid with ethanol and other drugs that depress the central nervous system (tricyclic antidepressants, MAO inhibitors and antipsychotic drugs), it is possible to increase the depression of the central nervous system.

Ethanol and other hepatotoxic drugs increase the likelihood of developing liver damage.

Valproic acid does not induce hepatic enzymes and does not reduce the effectiveness of oral contraceptives.

When combined with phenobarbitate, phenytoin, carbamazepine, mefloquine, the content of valproic acid in the blood serum decreases.

When combined with myelotoxic agents, the risk of inhibition of bone marrow hematopoiesis increases.