Depakin Enteric 300 tablets 300mg, No. 100

• Epileptic seizures: generalized, focal (focal, partial) with simple and complex symptoms, small.

• Convulsive syndrome in organic brain diseases.

• Conduct disorders associated with epilepsy.

• Manic-depressive psychosis with a bipolar course that does not respond to treatment with lithium or other drugs.

• Febrile seizures in children, children's tics.

Individual. For oral administration in adults and children weighing more than 25 kg, the initial dose is 10-15 mg / kg / day. Then the dose is gradually increased by 200 mg / day with an interval of 3-4 days until a clinical effect is achieved. The average daily dose is 20-30 mg / kg. For children weighing less than 25 kg and newborns, the average daily dose is 20-30 mg / kg. The frequency of administration is 2-3 times / day with meals.

Enteric-coated tablets are white, round, biconvex.

1 tab.

sodium valproate 300 mg

Excipients: povidone K-90 (polyvidone K-90) - 8 mg, calcium silicate hydrate - 15 mg, talc - 9 mg, magnesium stearate - 3 mg.

• Severe liver dysfunction;

• severe dysfunction of the pancreas;

• porphyria;

• hemorrhagic diathesis;

• severe thrombocytopenia;

• I trimester of pregnancy;

• lactation (breastfeeding);

• hypersensitivity to valproic acid.

pharmachologic effect

Antiepileptic drug. It is believed that the mechanism of action is associated with an increase in the content of GABA in the central nervous system, which is due to inhibition of GABA transaminase, as well as a decrease in the reuptake of GABA in brain tissues. This, apparently, leads to a decrease in the excitability and convulsive readiness of the motor zones of the brain. It helps to improve the mental state and mood of patients.

Pharmacokinetics

Valproic acid is rapidly and almost completely absorbed from the gastrointestinal tract, oral bioavailability is about 93%. Food intake does not affect the degree of absorption. Cmax in blood plasma is achieved in 1-3 hours. The therapeutic concentration of valproic acid in blood plasma is 50-100 mg / l.

Css is achieved on days 2-4 of treatment, depending on the intervals between doses. Plasma protein binding is 80-95%. Cerebrospinal fluid concentration levels correlate with the size of the non-protein bound fraction. Valproic acid crosses the placental barrier and is excreted in breast milk.

Metabolized by glucuronidation and oxidation in the liver.

Valproic acid (1-3%) and its metabolites are excreted by the kidneys. T1 / 2 with monotherapy and in healthy volunteers is 8-20 hours.

When combined with other drugs, T1 / 2 can be 6-8 hours due to the induction of metabolic enzymes.

Side effect

From the side of the central nervous system: trembling of the hands or arms is possible; rarely - changes in behavior, mood or mental state, diplopia, nystagmus, spots before the eyes, impaired coordination of movements, dizziness, drowsiness, headache, unusual agitation, restlessness or irritability.

On the part of the digestive system: mild cramps in the abdomen or in the stomach, loss of appetite, diarrhea, indigestion, nausea, vomiting are possible; rarely - constipation, pancreatitis.

From the side of the blood coagulation system: thrombocytopenia, prolonged bleeding time.

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

On the part of the gynecological status: menstrual irregularities.

Dermatological reactions: alopecia.

Allergic reactions: skin rash.

Application during pregnancy and lactation

Use during pregnancy is not recommended, especially in the first trimester. It should be borne in mind that valproic acid can cause various congenital anomalies, especially spina bifida.

Valproic acid is excreted in breast milk. There are reports that the concentration of valproate in breast milk was 1-10% of the concentration in the mother's blood plasma. Use during breastfeeding is contraindicated.

Women of childbearing age are advised to use reliable methods of contraception during treatment.

Application for violations of liver function

Contraindicated in liver dysfunction, acute and chronic hepatitis. Use with caution in case of liver disease in history.

It should be borne in mind that the risk of side effects from the liver is increased with combined anticonvulsant therapy. During the period of treatment, it is necessary to regularly monitor liver function.

Application for impaired renal function

Use with caution in case of impaired renal function.

Application in children

Children are at increased risk of developing severe or life-threatening hepatotoxic effects. The risk is even higher in patients under 2 years of age and in children receiving combination therapy, but decreases with age.

special instructions

It is used with caution in patients with pathological changes in the blood, with organic brain diseases, a history of liver disease, hypoproteinemia, and impaired renal function.

In patients receiving other anticonvulsants, valproic acid treatment should be started gradually, reaching a clinically effective dose after 2 weeks. Then carry out a gradual cancellation of other anticonvulsants. In patients who have not received treatment with other anticonvulsants, the 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 with combined anticonvulsant therapy.

During the period of treatment, it is necessary to regularly monitor the liver function, the picture of peripheral blood, the state of the blood coagulation system (especially during the first 6 months of treatment).

Children are at increased risk of developing severe or life-threatening hepatotoxic effects. In patients under the age of 2 years and in children receiving combination therapy, the risk is even higher, but it decreases with increasing age.

Influence on the ability to drive vehicles and use mechanisms

During the period of treatment, care should be taken when driving vehicles and other activities that require a high concentration of attention and quick psychomotor reactions.

Drug interactions

With the simultaneous use of antipsychotics, antidepressants, MAO inhibitors, benzodiazepine derivatives, ethanol, the inhibitory effect on the central nervous system is enhanced.

With the simultaneous use of agents with a hepatotoxic effect, it is possible to increase the hepatotoxic effect.

With simultaneous use, the effects of antiplatelet agents (including acetylsalicylic acid) and anticoagulants are enhanced.

With simultaneous use, the concentration of zidovudine in the blood plasma increases, which leads to an increase in its toxicity.

With simultaneous use with carbamazepine, the concentration of valproic acid in the blood plasma decreases due to an increase in its metabolic rate due to the induction of microsomal liver enzymes under the influence of carbamazepine. Valproic acid potentiates the toxic effect of carbamazepine.

With simultaneous use, the metabolism of lamotrigine slows down and its T1 / 2 increases.

With simultaneous use with mefloquine, the metabolism of valproic acid in the blood plasma increases and the risk of seizures increases.

With simultaneous use with meropenem, it is possible to reduce the concentration of valproic acid in the blood plasma; with primidone - an increase in the concentration of primidone in the blood plasma; with salicylates - it is possible to enhance the effects of valproic acid due to its displacement by salicylates from the connection with blood plasma proteins.

With simultaneous use with felbamate, the concentration of valproic acid in the blood plasma increases, which is accompanied by manifestations of toxic effects (nausea, drowsiness, headache, decreased platelet count, cognitive impairment).

With simultaneous use with phenytoin during the first few weeks, the total concentration of phenytoin in blood plasma may decrease due to its displacement from the sites of binding to plasma proteins by sodium valproate, induction of liver microsomal enzymes and acceleration of phenytoin metabolism. Further, there is an inhibition of the metabolism of phenytoin by valproate and, as a result, an increase in the concentration of phenytoin in the blood plasma. Phenytoin reduces the concentration of valproate in the blood plasma, probably by increasing its metabolism in the liver. It is believed that phenytoin, as an inducer of hepatic enzymes, may also increase the formation of a minor but hepatotoxic metabolite of valproic acid.

With the simultaneous use of valproic acid displaces phenobarbital from the connection with plasma proteins, as a result, its concentration in the blood plasma increases. Phenobarbital increases the metabolic rate of valproic acid, which leads to a decrease in its concentration in blood plasma.

There are reports of an increase in the effects of fluvoxamine and fluoxetine when used simultaneously with valproic acid. With simultaneous use with fluoxetine, an increase or decrease in the concentration of valproic acid in the blood plasma was observed in some patients.

With the simultaneous use of cimetidine, erythromycin, it is possible to increase the concentration of valproic acid in the plasma by reducing its metabolism in the liver.