How to replace depakine from the list of drugs. Depakin. Various forms of generalized seizures

pharmachologic effect

Antiepileptic drug. It is believed that the mechanism of action is associated with an increase in the content of GABA in the CNS, which is due to the inhibition of GABA transaminase, as well as a decrease in the reuptake of GABA in the brain tissues. This, apparently, leads to a decrease in the excitability and convulsive readiness of the motor areas of the brain. 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%. Eating does not affect the degree of absorption. C max in blood plasma is reached after 1-3 hours. Therapeutic concentration of valproic acid in blood plasma is 50-100 mg/l.

C ss is achieved on days 2-4 of treatment, depending on the intervals between doses. Plasma protein binding is 80-95%. The concentration levels in the cerebrospinal fluid 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. T 1/2 with monotherapy and in healthy volunteers is 8-20 hours.

When combined with other drugs T 1/2 may be 6-8 hours due to the induction of metabolic enzymes.

Indications

Epileptic seizures: generalized, focal (focal, partial) with simple and complex symptoms, small. Convulsive syndrome in organic diseases of the brain. Behavioral disorders associated with epilepsy. Manic-depressive psychosis with a bipolar course, not amenable to treatment with lithium or other drugs. Febrile convulsions in children, children's tick.

Dosing regimen

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 during meals.

In / in (in the form of sodium valproate) is administered at a dose of 400-800 mg or drip at the rate of 25 mg / kg for 24, 36 and 48 hours. at a dose of 0.5-1 mg / kg / h 4-6 hours after the last oral administration.

Maximum doses: when taken orally for adults and children weighing more than 25 kg - 50 mg / kg / day. Application at a dose of more than 50 mg / kg / day is possible subject to control of the concentration of valproate in the blood plasma. At plasma concentrations of more than 200 mg / l, the dose of valproic acid should be reduced.

Side effect

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

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

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

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

From the gynecological status: menstrual irregularities.

Dermatological reactions: alopecia.

Allergic reactions: skin rash.

Contraindications for use

Violations of the liver and pancreas, hemorrhagic diathesis, acute and chronic hepatitis, porphyria; hypersensitivity to valproic acid.

Use during pregnancy and lactation

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 maternal plasma. During lactation, the use is possible in cases of emergency.

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

Use in children

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

Overdose

Symptoms: coma with muscular hypotension, hyporeflexia, miosis, respiratory depression, metabolic acidosis; cases of intracranial hypertension associated with cerebral edema have been described. Symptoms may vary, and seizures have been reported with very high plasma concentrations of valproic acid.

With a significant overdose, a fatal outcome is possible, but the prognosis is usually favorable.

Treatment: in the hospital - gastric lavage, which is effective for 10-12 hours after ingestion of the contents of the vial with lyophilisate or solution for intravenous administration; monitoring and correction of the functional state of the cardiovascular and respiratory systems, maintaining effective diuresis. Naloxone has been used successfully in some cases. In very severe cases of significant overdose, hemodialysis and hemoperfusion have been effective.

drug interaction

With the simultaneous use of neuroleptics, antidepressants, MAO inhibitors, benzodiazepine derivatives, ethanol, the inhibitory effect on the central nervous system increases.

With the simultaneous use of drugs 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 the rate of its metabolism, 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 T 1/2 increases.

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

With simultaneous use with meropenem, a decrease in the concentration of valproic acid in the blood plasma is possible; 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 its association with plasma proteins.

With simultaneous use with felbamate, the concentration of valproic acid in the blood plasma increases, which is accompanied by manifestations of a toxic effect (nausea, drowsiness, headache, a decrease in the number of platelets, cognitive impairment).

With simultaneous use with phenytoin during the first few weeks, the total concentration of phenytoin in the blood plasma may decrease due to its displacement from the binding sites with plasma proteins by sodium valproate, induction of microsomal liver 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 plasma concentrations of valproate, 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 simultaneous use, valproic acid displaces phenobarbital from its association with plasma proteins, as a result, its concentration in blood plasma increases. Phenobarbital increases the rate of metabolism 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 they are used simultaneously with valproic acid. With simultaneous use with fluoxetine in some patients, an increase or decrease in the concentration of valproic acid in the blood plasma was observed.

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

Terms of dispensing from pharmacies

The drug is dispensed by prescription.

Terms and conditions of storage

The drug should be stored out of the reach of children at a temperature not exceeding 25°C. Shelf life - 5 years.

Application for violations of liver function

Contraindicated in violation of liver function, acute and chronic hepatitis. Use with caution in a history of liver disease.

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

Application for violations of kidney function

Use with caution in violations of kidney function.

special instructions

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

In patients receiving other anticonvulsants, treatment with valproic acid should be started gradually, reaching a clinically effective dose after 2 weeks. Then carry out a gradual abolition of other anticonvulsants. In patients not treated with other anticonvulsants, a clinically effective dose should be reached after 1 week.

It should be borne in mind that the risk of developing side effects from the liver is increased during combined anticonvulsant therapy.

During the period of treatment, it is necessary to regularly monitor 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 severe or life-threatening hepatotoxicity. In patients under the age of 2 years and in children receiving combination therapy, the risk is even higher, but with increasing age it decreases.

Influence on the ability to drive vehicles and control 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.

Depakine is a derivative of valproic acid. It affects both the membranes of brain neurons and its inhibitory system, activating the release of inhibitory mediators. It is used to treat convulsive seizures of any etiology, epilepsy and status epilepticus.

In this article, we will consider why doctors prescribe Depakine, including instructions for use, analogues and prices for this drug in pharmacies. Real REVIEWS of people who have already used Depakine can be read in the comments.

Composition and form of release

Depakine is available in the form of white coated tablets, 0.2 g each, packed in 40 pieces per vial or in ivory coated tablets, as well as in the form of a syrup.

1 tablet Depakine contains 0.2 or 0.5 g of valproic acid and excipients.

Clinico-pharmacological group: anticonvulsant drug.

What is Depakine used for?

Indications for the appointment of Depakine are:

Behavioral disorders due to epilepsy.
Convulsive syndrome in organic pathologies of the brain.
Children's tic, febrile convulsions in children.
Bipolar manic-depressive psychosis, not amenable to therapy with lithium or other drugs.
Focal and generalized epileptic seizures with simple and complex symptoms.

The injectable dosage form of the drug is indicated for the temporary replacement of its oral forms (if their use is not possible).

pharmachologic effect

Anticonvulsant drug, has a central muscle relaxant and sedative effect. Shows antiepileptic activity in all types of epilepsy.

The main mechanism of action seems to be related to the effect of valproic acid on the GABA-ergic system: the drug increases the content of GABA in the CNS and activates GABA-ergic transmission.

Therapeutic efficacy begins with a minimum concentration of 40-50 mg/l and can reach 100 mg/l. At a concentration of more than 200 mg / l, a dose reduction is necessary.

Instructions for use

According to the instructions for use, before starting therapy with Depakine, and also periodically during the first 6 months of using Depakine, it is necessary to conduct a study of liver function, especially in patients at risk.

Depakine tablets are taken orally, without chewing and with half a glass of water, before meals or immediately after it, two to three times a day. The dosage is set individually by the attending physician, depending on the severity of the symptoms and the effectiveness of the therapy.
The drug in syrup is mixed with food or any liquid before use. The drug is prescribed for adults and children weighing more than 25 kg. The initial dose of the drug should be 5-15 mg / kg per day, gradually increase this dose by 5-10 mg / kg per week.
Depakine Chrono is intended only for adults and children over 6 years of age weighing more than 17 kg! It is a sustained release dosage form, which avoids sharp rises in the concentration of valproic acid in the blood after taking the drug and maintains a constant concentration of valproic acid in the blood for a longer period of time.

Valproic acid in patients taking anticonvulsants should be given at the lowest dose, gradually adjusted to the required dose over 2 weeks. Cancellation of anticonvulsants should also be carried out gradually. In patients who are not taking anticonvulsants, an effective dose of Depakine can be reached after 1 week.

Contraindications

When using Depakine, it is necessary to take into account such contraindications as:

Hepatitis in any form;
Diseases of the pancreas;
Thrombocytopenia, leukopenia;
Individual sensitivity of the body to the components of the drug;
Impaired liver function;
Porfiria;
Diathesis hemorrhagic;
The period of pregnancy and lactation;
Age up to 6 months;
Age up to 3 years - do not prescribe the drug in injections.

Depakine should be used with caution in kidney diseases.

Side effects

When taking this medicine, the following side effects are possible:

thrombocytopenia;
mild hand tremor;
vasculitis;
hair loss;
drowsiness;
weight gain;
polymorphic erythema;
allergic reactions;
Stevens-Johnson syndrome;
confusion;
nausea;
stomach ache;
moderate hyperammonemia (not affecting the liver and not requiring cancellation of the course);
vomit;
diarrhea;
a decrease in fibrinogen levels or an increase in bleeding time;
headache.

Overdose symptoms: depression of consciousness up to coma, with loss of muscle tone, decreased reflexes, constriction of the pupils, respiratory depression, convulsive seizures.

Depakin's analogs

Structural analogues for the active substance:

Valparin;
sodium valproate;
Depakine chrono;
Depakine Chronosphere;
Depakine enteric 300;
Dipromal;
Convulsofin;
Encorate;
Encorat chrono.

Attention: the use of analogues must be agreed with the attending physician.

Prices

The average price of DEPAKIN, syrup in pharmacies (Moscow) is 290 rubles. Depakine Chrono, 500 mg tablets cost 580-650 rubles.

Ira
My son developed a severe form of epilepsy (as the neurologist told us) and Depakin recommended it. He has a lot of side effects, as many contraindications. They didn’t want to, but they accepted it, since there was nowhere to go anyway, it was not the life of a child. Now the son is unrecognizable. She enjoys life, the side effects from the declared did not appear. I want to believe someone helped in the choice.
Semyon
I think it's a good drug. Not the first time I take it, they really help. Everything happens at once. Previously, the attacks were 1 - 2 times a month, and such ... .. as if a grenade exploded in the head, the tongue was bitten so that then for a week you can’t really speak or eat, and after an attack for half a day you don’t understand where you are and who is around …. Now 1 - 2 times a year, while in a dream, and in the morning in most cases, normal consciousness and nothing hurts, I learn about an attack from relatives. Just do not think that one tablet will help you, take the drug regularly. Thank you, I shared my impressions, maybe it will help some of you.
Dima
Hello! my friend fell ill with epilepsy after he insulted Jesus at my house, saying that he hit him on the altar. .After many years, my friends and I realized that drugs did not help him, but the prayer of one girl who fell in love with him helped. Later, we all became witnesses to the fact that if a person is without the protection of God, then he begins to be overcome by all kinds of convulsions, epilepsy. When he was sausage, there was a feeling that he was being strangled. red head, burst blood vessels, bitten tongue. and now my friend's condition is quite normal, everything has passed, only they parted with that girl. Epilepsy, in my opinion, is a spiritual problem when demons have access to the body of a chela. inconceivable.
?Stalker
Useless drug, only to keep drug dealers alive
vladimir
I have been taking Depakine Chrono 500 for the third year (with a weight of 90 kg, the dose is 1000 mg), 500 mg 2 times a day with meals. During this time, there were no seizures, a side effect is hair loss. became noticeable (you can shave and the bald patch on the back of the head will not be visible). The absence of seizures makes you think about lowering the dose, but only after consulting with your doctor. There are drugs cheaper, but I don’t risk changing, it’s scary, attacks will suddenly resume. You get used to good things quickly.
Veronica
I have bipolar disorder. Doctors could not make a diagnosis for 10 years. During this time, all my friends and acquaintances turned away from me. Ogi saw that something was wrong with me. But I don’t see myself from the outside. Then I found a private arach and he prescribed me depakin. This medicine really helps. I took 1000. Now 500 for the night. Very slow. But sometimes there are breakdowns. I was left without friends. There are suspicions at work. But I'm holding on From depakin severe headaches.
Veronica
I have bipolar disorder. Doctors could not make a diagnosis for 10 years. During this time, all my friends and acquaintances turned away from me. They saw that something was wrong with me. But I don't see myself. Then I found a private arach and he prescribed me depakin. This medicine really helps. I took 1000. Now 500 at night. Helps a lot. But sometimes there are breakdowns. I was left without friends. There are suspicions at work. But I'm holding on From depakin severe headaches.
Elena
My mother was prescribed this drug, she is 67 years old, fell ill about 2 years ago, we work with her and at first I alone saw seizures, the rest of the family did not. Yes, and seizures are not like ordinary epilepsy, but she just fell into a stupor, stopped, did not react to external signs, completely blackout, does not hear, does not see, but characteristically did not fall, always in an upright position. Of the side effects, hair loss, and there were no attacks after the appointment.

In this article, you can read the instructions for using the drug Depakine. Reviews of site visitors - consumers of this medicine, as well as opinions of doctors of specialists on the use of Depakine in their practice are presented. A big request to actively add your reviews about the drug: did the medicine help or not help get rid of the disease, what complications and side effects were observed, perhaps not declared by the manufacturer in the annotation. Analogues of Depakine in the presence of existing structural analogues. Use for the treatment of epilepsy, tics and manic-depressive psychosis in adults, children, and during pregnancy and lactation.

Depakine- an antiepileptic drug. It is believed that the mechanism of action is associated with an increase in the content of GABA in the CNS, which is due to the inhibition of GABA transaminase, as well as a decrease in the reuptake of GABA in the brain tissues. This, apparently, leads to a decrease in the excitability and convulsive readiness of the motor areas of the brain. Helps to improve the mental state and mood of patients.

Compound

Sodium valproate + excipients.

Sodium valproate + Valproic acid + excipients (Chronosphere granules and Chrono tablets).

Pharmacokinetics

The bioavailability of valproate when administered orally is close to 100%. Food intake does not affect the pharmacokinetic profile. Plasma protein binding is high, dose-dependent and saturable. Valproate penetrates into the cerebrospinal fluid and into the brain. Valproate is predominantly excreted in the urine as a glucuronide.

Indications

In adults (as monotherapy or in combination with other antiepileptic drugs):

manic-depressive psychosis with a bipolar course, not amenable to treatment with lithium preparations or other drugs;
Lennox-Gastaut syndrome.

In infants (from 6 months of life) and children (as monotherapy or in combination with other antiepileptic drugs):

for the treatment of generalized epileptic seizures: clonic, tonic, tonic-clonic, absences, myoclonic, atonic; Lennox-Gastaut syndrome;
for the treatment of partial epileptic seizures: partial seizures with or without secondary generalization;
prophylaxis of convulsions at high temperature, when such prophylaxis is necessary;
Lennox-Gastaut syndrome;
baby tick.

Release form

Granules of prolonged action 100 mg, 250 mg, 500 mg, 750 mg and 1000 mg (Depakine Chronosphere).

Long-acting film-coated tablets 300 mg and 500 mg (Chrono).

Syrup (ideal children's form of the drug).

300 mg film-coated tablets (Enteric).

Lyophilizate for the preparation of a solution for intravenous administration (injections in ampoules for injection).

Instructions for use and method of use

Individual. For oral administration in adults and children weighing more than 25 kg, the initial dose is 10-15 mg / kg per day. Then the dose is gradually increased by 200 mg per 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.

Frequency of administration - 2-3 times a day with meals.

Intravenously (in the form of sodium valproate) is administered at a dose of 400-800 mg or drip at the rate of 25 mg / kg for 24, 36 and 48 hours. 0.5-1 mg / kg / h 4-6 hours after the last oral administration.

Maximum doses: when taken orally for adults and children weighing more than 25 kg - 50 mg / kg per day. Application at a dose of more than 50 mg / kg per day is possible subject to control of the concentration of valproate in the blood plasma. At plasma concentrations of more than 200 mg / l, the dose of valproic acid should be reduced.

Syrup

Inside (1 bilateral dosing spoon of syrup contains sodium valproate 100 or 200 mg). The initial daily dose is 10-15 mg / kg, then the doses are gradually increased to optimal concentrations.

Usually the optimal dose is 20-30 mg/kg. However, if the seizures do not stop, the dose can be increased adequately; careful monitoring of patients receiving doses above 50 mg/kg is necessary.

For children, the usual dose is about 30 mg/kg per day.

Adults - 20-30 mg / kg per day.

Depakine syrup can be administered twice a day.

Granules Chronosphere

Depakine Chronosphere is a dosage form that is particularly well suited for the treatment of children (if they are able to swallow soft foods) or adults with difficulty swallowing.

The drug is prescribed inside. The daily dose is determined depending on the age and body weight of the patient, should also take into account a wide range of individual sensitivity to valproate.

The initial daily dose is 10-15 mg / kg of body weight, then it is increased by 5-10 mg / kg per week until the optimal dose is reached.

The average daily dose is 20-30 mg/kg. It is possible to increase the dose of the drug with careful monitoring of the patient's condition, if epilepsy cannot be controlled using average daily doses.

The average daily dose for adults is 20 mg/kg; for teenagers - 25 mg / kg; for children, incl. infants (starting from 6 months of life) - 30 mg / kg.

Rules for the use of the drug

Depakine Chronosphere in sachets of 100 mg is used only in children and infants. Depakine Chronosphere in sachets of 1 g is used only in adults.

The contents of the sachet should be poured onto the surface of soft food or drinks at cold or room temperature (including yogurt, orange juice, fruit puree, etc.). If Depakine Chronosphere is taken with liquid, it is recommended to rinse the glass with a small amount of water and drink this water, because. the granules may stick to the glass. The mixture should always be swallowed immediately, without chewing. It should not be stored for later use.

Depakine Chronosphere should not be used with hot food or drinks (such as soups, coffee, tea, etc.). The drug Depakine Chronosphere cannot be poured into a bottle with a nipple, because. the granules can clog the opening of the nipple.

Given the duration of the release process of the active substance and the nature of the excipients, the inert matrix of the granule is not absorbed from the digestive tract; it is excreted in the feces after the complete release of the active substance.

Chrono tablets

Depakine Chrono is a dosage form with a delayed release of the active substance, which provides more uniform concentrations throughout the day compared to conventional Depakine dosage forms.

The drug is taken orally. The daily dose is recommended to be taken in 1 or 2 doses, preferably with meals.

The dose should be set in accordance with the age and body weight of the patient, as well as taking into account individual sensitivity to the drug.

A good correlation has been established between the daily dose, serum concentration of the drug and the therapeutic effect, so the optimal dose should be determined depending on the clinical response. Determination of plasma valproic acid concentration can be considered as an adjunct to clinical monitoring when epilepsy is not controlled or side effects are suspected. The range of concentrations at which a clinical effect is observed is usually 40-100 mg/l (300-700 µmol/l).

For adults and children weighing more than 17 kg, the initial daily dose is usually 10-15 mg / kg of body weight, then the dose is increased to the optimum. The average dose is 20-30 mg / kg per day. In the absence of a therapeutic effect (if the seizures do not stop), the dose can be increased; this requires careful monitoring of the patient's condition.

For children aged 6 years and older, the average daily dose is 30 mg/kg.

In elderly patients, the dose should be adjusted according to their clinical condition.

Tablets are taken without crushing or chewing them.

Application in 1 dose is possible with well-controlled epilepsy.

When switching from immediate-release tablets of valproate, which provided the necessary control over the disease, to the sustained release form (Depakine Chrono), the daily dose should be maintained.

Replacement of other antiepileptic drugs with Depakine Chrono should be carried out gradually, reaching the optimal dose of valproate within about 2 weeks. In this case, depending on the patient's condition, the dose of the previous drug is reduced.

For patients not taking other antiepileptic drugs, doses should be increased after 2-3 days in order to reach the optimal dose within about a week.

If necessary, a combination with other anticonvulsants against the background of the use of Depakine Chrono, such drugs should be administered gradually.

Side effect

trembling of the hands or arms;
changes in behavior, mood or mental state;
nystagmus;
spots before the eyes;
violations of coordination of movements;
dizziness;
drowsiness;
headache;
unusual arousal;
motor restlessness;
irritability;
mild cramps in the abdomen or in the stomach area;
loss of appetite;
diarrhea;
digestive disorders;
nausea, vomiting;
constipation;
thrombocytopenia, prolongation of bleeding time;
an unusual decrease or increase in body weight;
menstrual irregularities;
alopecia;
skin rash.

Contraindications

dysfunction of the liver and pancreas;
hemorrhagic diathesis;
acute and chronic hepatitis;
porphyria;
children's age up to 6 months (granules); children under 6 years of age for tablets (risk of inhalation if swallowed);
hypersensitivity to valproic acid.

Use during pregnancy and lactation

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

Use in children

special instructions

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

It should be borne in mind that the risk of developing side effects from the liver is increased during combined anticonvulsant therapy.

Influence on the ability to drive vehicles and control 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 interaction

With the simultaneous use of neuroleptics, antidepressants, MAO inhibitors, benzodiazepine derivatives, ethanol (alcohol), the inhibitory effect on the central nervous system increases.

With the simultaneous use of drugs 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, the metabolism of lamotrigine slows down.

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

With the simultaneous use of Depakine with phenytoin during the first few weeks, the total concentration of phenytoin in the blood plasma may decrease due to its displacement from the sites of binding to plasma proteins with sodium valproate, induction of microsomal liver enzymes and acceleration of the metabolism of phenytoin. 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 plasma concentrations of valproate, 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 cimetidine, erythromycin, it is possible to increase the concentration of valproic acid in plasma by reducing its metabolism in the liver.

Analogues of the drug Depakine

Structural analogues for the active substance:

Valparin;
sodium valproate;
Depakine chrono;
Depakine Chronosphere;
Depakine enteric 300;
Dipromal;
Convulex;
Convulsofin;
Encorate;
Encorat chrono.

In the absence of analogues of the drug for the active substance, you can follow the links below to the diseases that the corresponding drug helps with and see the available analogues for the therapeutic effect.

Ethosuximide

To compile a list of cheap analogues of expensive drugs, we use the prices provided by more than 10,000 pharmacies throughout Russia. The database of drugs and their analogues is updated daily, so the information provided on our website is always up-to-date as of the current day. If you have not found the analogue you are interested in, please use the search above and select the medicine you are interested in from the list. On the page of each of them you will find all possible options for analogues of the desired medicine, as well as prices and addresses of pharmacies in which it is available.

How to find a cheap analogue of an expensive medicine?

To find an inexpensive analogue of a drug, a generic or a synonym, we first of all recommend paying attention to the composition, namely to the same active ingredients and indications for use. The same active ingredients of the drug will indicate that the drug is a synonym for the drug, a pharmaceutical equivalent or a pharmaceutical alternative. However, do not forget about the inactive components of similar drugs, which can affect safety and efficacy. Do not forget about the advice of doctors, self-medication can harm your health, so always consult a doctor before using any medication.

Depakine Chronosphere price

On the sites below you can find prices for Depakine Chronosphere and find out about availability at a pharmacy nearby

Depakine Chronosphere instruction

INSTRUCTIONS
on the use of the drug
Depakine Chronosphere

ATC code: N03AG01 (Valproic acid)

Active substance: valproic acid

Release form, composition and packaging

1 pack
sodium valproate66.66 mg

valproic acid29.03 mg

In terms of sodium valproate 100 mg

Excipients: solid paraffin - 101.26 mg, glycerol dibegenate - 106.05 mg, colloidal silicon dioxide water *.

Sustained-release granules, almost white or slightly yellowish, waxy, free-flowing, without agglomeration.

sodium valproate 166.76 mg

valproic acid 72.61 mg

In terms of sodium valproate 250 mg

Excipients: solid paraffin - 253.32 mg, glycerol dibehenate - 265.3 mg, colloidal silicon dioxide water *.

Three-layer bags (30) - packs of cardboard.

Three-layer bags (50) - packs of cardboard.

Sustained-release granules, almost white or slightly yellowish, waxy, free-flowing, without agglomeration.

sodium valproate333.3 mg

valproic acid 145.14 mg

In terms of sodium valproate 500 mg

Excipients: solid paraffin - 506.31 mg, glycerol dibehenate - 530.25 mg, colloidal silicon dioxide water *.

Three-layer bags (30) - packs of cardboard.

Three-layer bags (50) - packs of cardboard.

Sustained-release granules, almost white or slightly yellowish, waxy, free-flowing, without agglomeration.

sodium valproate500.06 mg

valproic acid 217.75 mg

In terms of sodium valproate 750 mg

Excipients: solid paraffin - 759.64 mg, glycerol dibehenate - 795.55 mg, colloidal silicon dioxide water *.

Three-layer bags (30) - packs of cardboard.

Three-layer bags (50) - packs of cardboard.

Sustained-release granules, almost white or slightly yellowish, waxy, free-flowing, without agglomeration.

sodium valproate666.6 mg

valproic acid 290.27 mg

In terms of sodium valproate 1000 mg

Excipients: solid paraffin - 1012.63 mg, glycerol dibegenate - 1060.5 mg, colloidal silicon dioxide water *.

* added by spraying after the melt cooling process and expressed as a percentage of the amount of the other four components: 0.7% (approximate amount absorbed on the granules: 0.56%).

Clinico-pharmacological group:
Anticonvulsant drug

Pharmaco-therapeutic group:
Antiepileptic

pharmachologic effect

Antiepileptic drug, has a central muscle relaxant and sedative effect.

Shows antiepileptic activity in various types of epilepsy. The main mechanism of action seems to be related to the effect of valproic acid on the GABA-ergic system: it increases the content of GABA in the CNS and activates GABA-ergic transmission.

Depakine® Chronosphere™ is a prolonged action granules that provide more uniform drug concentrations throughout the day.

Pharmacokinetics

Suction

The bioavailability of valproic acid when administered orally is close to 100%. Food intake does not affect the pharmacokinetic profile. Cmax of the drug in plasma is reached approximately 7 hours after ingestion.

Compared with the enteric-coated dosage form, equivalent doses of Depakine® Chronosphere™ are characterized by longer absorption, identical bioavailability, a more linear correlation between doses and plasma concentration of valproic acid (total concentration and free fraction concentration). In addition, Cmax and Cmax of the free fraction of valproic acid in plasma are lower (the decrease is about 25%), but there is a relatively more stable plateau phase of plasma concentrations from 4 to 14 hours after administration, the magnitude of fluctuations in plasma concentrations when taking Depakine ® Chronosphere™, compared to the enteric-coated dosage form, is halved, as a result of which valproic acid is more evenly distributed in the tissues during the day.

Serum concentrations of valproic acid of 40-100 mg / l (300-700 μmol / l) are usually effective (determined before taking the first dose of the drug during the day). At serum concentrations of valproic acid above 100 mg / l, an increase in side effects is expected, up to the development of intoxication.

Distribution

Vd depends on age and is usually 0.13-0.23 l / kg body weight, in young people 0.13-0.19 l / kg body weight. Due to the decrease in the magnitude of fluctuations in plasma concentrations when taking the drug Depakine® Chronosphere™, valproic acid is more evenly distributed in tissues during the day compared to the dosage form of valproic acid with immediate release.

The binding of valproic acid to plasma proteins (mainly albumin) is high (90-95%), dose-dependent and saturable. Valproic acid penetrates into the cerebrospinal fluid and into the brain. The concentration of valproic acid in the CSF is 10% of the corresponding concentration in the blood serum, that is, close to the concentration of the free fraction of valproic acid in the blood serum.

Valproic acid passes into the breast milk of nursing mothers. In the state of reaching the Css of valproic acid in the blood serum, its concentration in breast milk is up to 10% of its concentration in the blood serum.

Metabolism

Metabolism of valproic acid is carried out in the liver by glucuronidation, as well as beta-, omega-, and omega-1 oxidation. More than 20 metabolites have been identified, metabolites after omega-oxidation have a hepatotoxic effect.

Valproic acid does not have an inducing effect on enzymes that are part of the cytochrome P450 metabolic system: unlike most other antiepileptic drugs, valproic acid does not affect the degree of both its own metabolism and the degree of metabolism of other substances, such as estrogens, progestogens and indirect anticoagulants.

breeding

Valproic acid is predominantly excreted by the kidneys after conjugation with glucuronic acid and beta-oxidation.

When using valproic acid in monotherapy, its T1 / 2 is 12-17 hours. When combined with antiepileptic drugs that induce microsomal liver enzymes (such as primidone, phenytoin, phenobarbital and carbamazepine), the plasma clearance of valproic acid increases, and T1 / 2 decreases, the degree of their change depends on the degree of induction of microsomal liver enzymes by other antiepileptic drugs. T1 / 2 in children older than 2 months is close to that in adults.

Pharmacokinetics in special clinical situations

In elderly patients, patients with renal and hepatic insufficiency, binding to plasma proteins decreases.

In severe renal failure, the concentration of the free (therapeutically active) fraction of valproic acid may increase to 8.5-20%.

With hypoproteinemia, the total concentration of valproic acid (free + plasma protein-bound fraction) may not change, but may also decrease due to an increase in the metabolism of the free (non-plasma protein-bound) fraction of valproic acid.

In patients with liver disease, T1 / 2 of valproic acid increases.

In case of overdose, an increase in T1 / 2 up to 30 hours was observed. Only the free fraction of valproic acid in the blood (510%) is subjected to hemodialysis.

Features of pharmacokinetics during pregnancy

With an increase in Vd of valproic acid in the third trimester of pregnancy, its renal and hepatic clearance increases. At the same time, despite taking the drug at a constant dose, a decrease in serum concentrations of valproic acid is possible. In addition, during pregnancy, the relationship of valproic acid with plasma proteins may change, which can lead to an increase in the content of the free (therapeutically active) fraction of valproic acid in the blood serum.

Indications

In adults (as monotherapy or in combination with other antiepileptic drugs):

Lennox-Gastaut syndrome;

Treatment and prevention of bipolar affective disorders.

In infants (from 6 months of life) and children (as monotherapy or in combination with other antiepileptic drugs):

For the treatment of generalized epileptic seizures: clonic, tonic, tonic-clonic, absences, myoclonic, atonic;

Lennox-Gastaut syndrome;

For the treatment of partial epileptic seizures: partial seizures with or without secondary generalization;

Prevention of convulsions at high temperature, when such prophylaxis is necessary.

Dosing regimen

Depakine® Chronosphere™ is a dosage form that is particularly well suited for the treatment of children (if they are able to swallow soft foods) or adults with difficulty swallowing.

Depakine® Chronosphere™ is a prolonged action granules that provide more uniform concentrations of valproic acid in the blood and, accordingly, its more uniform distribution in tissues throughout the day.

Bipolar affective disorders

The dose should be selected and controlled by the attending physician individually. The daily dose should be set taking into account the age and body weight of the patient. The recommended starting dose is 20 mg (calculated as sodium valproate) per kg of body weight. The dose should be increased as quickly as possible to the minimum dose that provides the desired therapeutic effect.

The recommended maintenance dose for the treatment of bipolar disorder is between 1000 mg and 2000 mg (expressed as sodium valproate) per day. The dose should be adjusted according to the individual clinical response of the patient. For the prevention of manic states, an individually selected minimum clinically effective dose should be used.

Epilepsy

In monotherapy, the initial daily dose is usually 5-10 mg (in terms of sodium valproate) per kg of body weight, then it is increased by 5 mg / kg every 4-7 until the optimal dose is reached to prevent the onset of epileptic seizures.

Average daily dose:

for children under 14 years old - 30 mg / kg of body weight;

for adolescents 14-18 years old - 25 mg / kg of body weight;

for adults and elderly patients (body weight from 60 kg and above) - 20 mg / kg of body weight.

Age of patients Body weight Average daily dose*

Infants aged 6 to 12 monthsAbout 7.5-10 kg 150-300 mg

Children 1 to 3 years oldAbout 10-15 kg 300-450 mg

Children 3 to 6 years of ageAbout 15-25 kg 450-750 mg

Children from 7 to 14 years old About 25-40 kg 750-1200 mg

Adolescents from 14 years old About 40-60 kg1000-1500 mg

Adults 60 kg and above 1200-2100 mg

* dose in terms of the number of milligrams of sodium valproate

The average daily dose can be increased under the control of the concentration of valproic acid in the blood.

Although the daily dose is determined depending on the age and body weight of the patient, a wide range of individual sensitivity to valproic acid should be taken into account.

A clear correlation between the daily dose, the concentration of valproic acid in the blood serum and the therapeutic effect has not been established. Therefore, the optimal dose of the drug should be selected mainly on the basis of clinical response.

Determination of the concentration of valproic acid in the blood serum can serve as an addition to clinical observation in cases where epilepsy is not controlled or the development of side effects is suspected. Usually effective doses are those that provide serum concentrations of valproic acid of 40-100 mg / l (300-700 μmol / l). If there is a reasonable need to achieve higher serum concentrations, the ratio of the expected benefit and the risk of side effects, especially dose-dependent ones, should be carefully weighed. at serum concentrations of valproic acid above 100 mg / l, an increase in side effects is expected up to the development of intoxication. Therefore, the serum concentration determined before taking the first dose per day should not exceed 100 mg / l.

When switching from dosage forms of the drug Depakin® immediate release or sustained release, which well controlled epilepsy, to Depakin® Chronosphere ™, it is recommended to continue taking the same daily dose.

For patients who have previously taken antiepileptic drugs, the transfer to the drug Depakine® Chronosphere™ should be carried out gradually, reaching the optimal dose of the drug within about 2 weeks. At the same time, the dose of the previously taken antiepileptic drug, especially phenobarbital, is immediately reduced. If a previously taken antiepileptic drug is canceled, then its cancellation should be carried out gradually.

If it is necessary to combine valproic acid with other antiepileptic drugs, they should be added gradually.

Because other antiepileptic drugs can reversibly induce microsomal liver enzymes, it is necessary to monitor the concentration of valproic acid in the blood within 4-6 weeks after taking the last dose of these antiepileptic drugs and, if necessary (as the metabolism-inducing effect of these drugs decreases), reduce the daily dose of Depakine® Chronosphere ™.

Special patient groups

Female children and adolescents, women of childbearing potential and pregnant women: treatment with Depakine® Chronosphere™ should be initiated under the supervision of a specialist experienced in the treatment of epilepsy and bipolar disorders. Treatment should only be started if other treatments are ineffective or not tolerated, and the benefit-risk ratio should be carefully reassessed when treatment is regularly reviewed. It is preferable to use Depakine® preparations for monotherapy and in the smallest effective doses and, if possible, in sustained release dosage forms. During pregnancy, the daily dose should be divided into at least 2 single doses.

Although there are changes in the pharmacokinetics of valproic acid in elderly patients, they are of limited clinical significance and the dose of valproic acid in elderly patients should be selected in accordance with the achievement of control over epileptic seizures.

In patients with renal insufficiency and / or hypoproteinemia, the possibility of increasing the concentration of the free (therapeutically active) fraction of valproic acid in the blood serum should be considered, and if necessary, reduce the dose of valproic acid, focusing on dose selection, mainly on the clinical picture, and not on the general the content of valproic acid in the blood serum (free fraction and plasma protein-bound fraction together) to avoid possible errors in dose selection.

Mode of application

The drug is taken orally.

Depakine® Chronosphere™ 100 mg sachets are used only in children and infants.

Depakine® Chronosphere™ 1000 mg sachets are used only in adults.

Depakine® Chronosphere™ should be poured onto the surface of soft food or drink, cold or at room temperature (yogurt, orange juice, fruit puree, etc.).

Depakine® Chronosphere™ should not be used with hot food or drinks (such as soups, coffee, tea, etc.).

The drug Depakine® Chronosphere™ cannot be poured into a bottle with a nipple, because. the granules can clog the opening of the nipple.

If Depakine® Chronosphere™ is taken with liquid, it is recommended to rinse the glass with a small amount of water and drink this water, because. the granules may stick to the glass.

The mixture should always be swallowed immediately, without chewing. It should not be stored for later use.

Side effect

Determination of the frequency of adverse reactions (WHO classification): very often (≥10%), often (≥1% and<10%), нечасто (≥0.1% и <1%), редко (≥0.01% и <0.1%), очень редко (<0.01%), частота неизвестна (невозможно определить по имеющимся данным).

Congenital, hereditary and genetic disorders: teratogenic risk.

From the hematopoietic system: often - anemia, thrombocytopenia; infrequently - pancytopenia, leukopenia, neutropenia. Leukopenia and pancytopenia can be both with depression of bone marrow hematopoiesis, and without it. After discontinuation of the drug, the blood picture returns to normal.

From the blood coagulation system: often - bleeding and hemorrhage; rarely - a decrease in the content of blood coagulation factors (at least one), a deviation from the norm of blood coagulation indicators (such as an increase in prothrombin time, an increase in APTT, an increase in thrombin time, an increase in MHO). The appearance of spontaneous ecchymosis and bleeding require discontinuation of the drug and clinical and laboratory examination.

From the nervous system: very often - tremor; often - extrapyramidal disorders, stupor *, drowsiness, convulsions *, memory impairment, headache, nystagmus, dizziness (may occur a few minutes after an IV injection and disappear spontaneously within a few minutes); infrequently - coma *, encephalopathy *, lethargy *, reversible parkinsonism, ataxia, paresthesia, increased severity of seizures; rarely - reversible dementia, combined with reversible brain atrophy, cognitive disorders; frequency unknown - sedation.

* Stupor and lethargy sometimes led to transient coma/encephalopathy and were either isolated or associated with an increase in seizures during treatment, and also decreased when the drug was discontinued or when the dose was reduced. Most of these cases have been described against the background of combination therapy, especially with the simultaneous use of phenobarbital or topiramate, or after a sharp increase in the dose of valproic acid.

On the part of the psyche: infrequently - a state of confusion, aggressiveness **, agitation **, impaired attention **, depression (with a combination of valproic acid with other anticonvulsants); rarely - behavioral disorders **, psychomotor hyperactivity **, learning disabilities **, depression (with valproic acid monotherapy).

**adverse reactions, mainly observed in pediatric patients.

From the senses: often - reversible and irreversible deafness; frequency unknown - diplopia.

From the digestive system: very often - nausea; often - vomiting, gum changes (mainly gum hyperplasia), stomatitis, epigastric pain, diarrhea (which often occur in some patients at the beginning of treatment, but usually disappear after a few days and do not require discontinuation of therapy); infrequently - pancreatitis, sometimes fatal (the development of pancreatitis is possible during the first 6 months of treatment; in case of acute abdominal pain, it is necessary to control the activity of serum amylase); frequency unknown - abdominal cramps, anorexia, increased appetite. Frequent reactions from the digestive system can be reduced by taking the drug during or after a meal.

From the side of the liver and biliary tract: often - liver damage, which is accompanied by a deviation from the norm of indicators of the functional state of the liver, such as a decrease in the prothrombin index, especially in combination with a significant decrease in the content of fibrinogen and blood coagulation factors, an increase in the concentration of bilirubin and an increase in the activity of hepatic transaminases in blood; liver failure, in exceptional cases with a fatal outcome. It is necessary to monitor patients for possible violations of liver function.

From the respiratory system: infrequently - pleural effusion.

From the urinary system: infrequently - renal failure; rarely - enuresis, tubulointerstitial nephritis, reversible Fanconi syndrome (a complex of biochemical and clinical manifestations of renal tubular damage with impaired tubular reabsorption of phosphate, glucose, amino acids and bicarbonate), the development mechanism of which is still unclear.

From the immune system: often - hypersensitivity reactions, for example, urticaria; infrequently - angioedema; rarely - drug rash syndrome with eosinophilia and systemic symptoms (DRESS syndrome).

From the skin and subcutaneous tissues: often - transient or dose-dependent alopecia (including androgenetic alopecia against the background of developed hyperandrogenism, polycystic ovaries, as well as alopecia against the background of developed hypothyroidism), disorders of the nails and nail bed; infrequently - rash, hair disorders (such as a violation of the normal structure of the hair, a change in hair color, abnormal hair growth [the disappearance of waviness and curly hair or, conversely, the appearance of curly hair in individuals with initially straight hair]); rarely - toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme.

From the musculoskeletal system and connective tissue: infrequently - a decrease in bone mineral density, osteopenia, osteoporosis and fractures in patients taking valproic acid for a long time (the mechanism of the effect of valproic acid on bone metabolism has not been established); systemic lupus erythematosus.

From the endocrine system: infrequently - a syndrome of inadequate ADH secretion, hyperandrogenism (hirsutism, virilization, acne, male pattern alopecia and / or increased concentrations of androgens in the blood); rarely - hypothyroidism.

On the part of metabolism: often - hyponatremia, weight gain (because weight gain is a factor contributing to the development of polycystic ovary syndrome); rarely - hyperammonemia *, obesity.

* There may be cases of isolated and moderate hyperammonemia without changes in liver function and the need to stop treatment. It was also reported about the occurrence of hyperammonemia, accompanied by the appearance of neurological symptoms, incl. development of encephalopathy, vomiting, ataxia), which required discontinuation of valproic acid and additional examination.

From the side of the vessels: infrequently - vasculitis.

From the reproductive system: often - dysmenorrhea; infrequently - amenorrhea; rarely - male infertility, polycystic ovaries; frequency unknown - dysmenorrhea, breast enlargement, galactorrhea.

Benign, malignant and indeterminate tumors (including cysts and polyps): rarely - myelodysplastic syndrome.

General disorders: infrequently - hypothermia, mild peripheral edema.

Laboratory and instrumental data: rarely - biotin deficiency / biotinidase deficiency.

Contraindications for use

Hypersensitivity to sodium valproate, valproic acid, seminatrium valproate, valpromide or any of the auxiliary components of the drug;

Acute hepatitis;

chronic hepatitis;

Severe liver disease (especially drug-induced hepatitis) in the anamnesis of the patient and his close blood relatives;

Severe liver damage with a fatal outcome when using valproic acid in close blood relatives of the patient;

Severe liver dysfunction;

Severe dysfunction of the pancreas;

hepatic porphyria;

Established mitochondrial diseases caused by mutations in the nuclear gene encoding the mitochondrial enzyme γ-polymerase (POLG), such as Alpers-Huttenlocher syndrome, and suspected diseases due to defects in γ-polymerase, in children under 2 years of age;

Patients with established disorders of the carbamide cycle (urea cycle);

Hemorrhagic diathesis, thrombocytopenia;

Combination with mefloquine;

Combination with preparations of St. John's wort;

Children's age up to 6 months.

Carefully

Diseases of the liver and pancreas in history;

Pregnancy;

Congenital fermentopathy;

Inhibition of bone marrow hematopoiesis (leukopenia, thrombocytopenia, anemia);

Renal failure (dose adjustment required);

Hypoproteinemia;

Simultaneous use of several anticonvulsants (due to an increased risk of liver damage);

Concomitant use of drugs that provoke seizures or lower the seizure threshold, such as tricyclic antidepressants, selective serotonin reuptake inhibitors; phenothiazine derivatives, butyrophenone derivatives, chloroquine, bupropion, tramadol (risk of provoking seizures);

Simultaneous use of antipsychotics, MAO inhibitors, antidepressants, benzodiazepines (the possibility of potentiating their effects);

Concomitant use of phenobarbital, primidone, phenytoin, lamotrigine, zidovudine, felbamate, olanzapine, propofol, aztreonam, acetylsalicylic acid, indirect anticoagulants, cimetidine, erythromycin, carbapenems, rifampicin, nimodipine, rufinamide (especially in children), protease inhibitors (ritonavir, protease inhibitors) , cholestyramine (due to pharmacokinetic interaction at the level of metabolism or binding to plasma proteins, plasma concentrations of either these drugs and / or valproic acid may change);

Simultaneous administration with carbamazepine (risk of potentiation of the toxic effects of carbamazepine and a decrease in the plasma concentration of valproic acid);

Simultaneous reception with topiramate or acetazolamide (risk of encephalopathy);

In patients with pre-existing carnitine palmitoyltransferase (CPT) type II deficiency (higher risk of developing rhabdomyolysis when taking valproic acid).

Use during pregnancy and lactation

Pregnancy

Depakine® Chronosphere™ should not be used in female children and adolescents, women of childbearing age and pregnant women, unless other treatments are ineffective or not tolerated by the patient.

In women planning a pregnancy, every effort should be made before conception to transfer the patient to an appropriate alternative treatment, if possible.

The risk associated with the development of epileptic seizures during pregnancy. During pregnancy, the development of generalized tonic-clonic epileptic seizures, status epilepticus with the development of hypoxia may pose a particular risk, both for the mother and the fetus, due to the possibility of death.

The risk associated with the use of the drug Depakine® Chronosphere™ during pregnancy. Experimental reproductive toxicity studies in mice, rats, and rabbits have demonstrated that valproic acid is teratogenic.

Congenital malformations. The available clinical data have demonstrated a higher incidence of minor and severe malformations, in particular, congenital neural tube defects, craniofacial deformities, malformations of the limbs and the cardiovascular system, hypospadias, and multiple malformations affecting different organ systems in children born to mothers who took valproic acid during pregnancy, compared with their frequency when taken during pregnancy with a number of other antiepileptic drugs. Thus, the risk of congenital malformations in children born to mothers with epilepsy who received valproic acid monotherapy during pregnancy was approximately 1.5, 2.3, 2.3 and 3.7 times higher compared with monotherapy with phenytoin, carbamazepine, phenobarbital and lamotrigine, respectively.

Data from a meta-analysis that included registry and cohort studies showed that the incidence of congenital malformations in children born to mothers with epilepsy who received valproic acid monotherapy during pregnancy was 10.73% (95% confidence interval 8.16-13.29). This risk is greater than the risk of severe congenital malformations in the general population, which was 2-3%. This risk is dose dependent. but a threshold dose below which there is no such risk cannot be established.

Disorders of mental and physical development

It has been shown that intrauterine exposure to valproic acid may have undesirable effects on the mental and physical development of children exposed to such exposure. Apparently, this risk is dose-dependent, but it is not possible to establish a threshold dose below which there is no such risk. The exact gestational period for the risk of developing these effects has not been established, and the risk cannot be ruled out throughout pregnancy. Studies of preschool children exposed to valproic acid in utero have shown that up to 30-40% of these children had early developmental delays (such as delayed learning to walk and delayed speech development), as well as lower intellectual abilities, poor speech skills (own speech and speech comprehension) and memory problems.

The intelligence quotient (IQ index) measured in children aged 6 years with a history of intrauterine exposure to valproate was on average 7-10 points lower than in children exposed to intrauterine exposure to other antiepileptic drugs. Although the role of other factors that can adversely affect the intellectual development of children exposed to valproic acid in utero cannot be ruled out, it is clear that in such children the risk of intellectual impairment may be independent of the mother's IQ index.

Data on long-term outcomes are limited.

There is evidence that children exposed to valproic acid in utero have an increased risk of developing autism spectrum disorders (approximately 3-fold increased risk), including childhood autism (approximately 5-fold increased risk).

Limited evidence suggests that children exposed to valproic acid in utero are more likely to develop attention deficit/hyperactivity disorder (ADHD).

Valproic acid monotherapy and valproic acid-containing combination therapy are associated with poor pregnancy outcomes, but combination antiepileptic therapy that includes valproic acid has been reported to be associated with a higher risk of adverse pregnancy outcomes compared to valproic acid monotherapy (i.e. the risk of developing disorders in the fetus is less with the use of valproic acid when used as monotherapy).

Risk factors for fetal malformations are: a dose of more than 1000 mg / day (however, a lower dose does not eliminate this risk) and the combination of valproic acid with other anticonvulsants.

In connection with the foregoing, the drug Depakine® Chronosphere™ should not be used during pregnancy and in women of childbearing potential unless absolutely necessary, i.e. its use is possible only in situations where other antiepileptic drugs are ineffective or the patient does not tolerate them.

The question of the need to use the drug Depakin® Chronosphere ™ or the possibility of refusing its use should be decided before the start of the drug or reconsidered if a woman taking the drug Depakin® Chronosphere ™ is planning a pregnancy.

Women should be informed about the need for pregnancy planning and monitoring.

Women of childbearing potential should use effective contraceptive methods during treatment with Depakine® Chronosphere™.

Women of childbearing potential should be informed about the risks and benefits of using valproic acid during pregnancy.

If a woman is planning a pregnancy, or she is diagnosed with pregnancy, then the need for treatment with valproic acid should be reassessed depending on the indications.

When bipolar disorder is indicated, consideration should be given to discontinuing treatment with valproic acid.

When epilepsy is indicated, the question of continuing treatment with valproic acid or its withdrawal is decided after a reassessment of the benefit-risk ratio. If, after reassessing the balance of benefits and risks, treatment with Depakine® Chronosphere™ should still be continued during pregnancy, then it is recommended to use it at the minimum effective daily dose, divided into several doses. It should be noted that during pregnancy, the use of sustained release dosage forms is more preferable than other dosage forms.

If possible, even before pregnancy, you should additionally start taking folic acid (at a dose of 5 mg / day), because. folic acid may reduce the risk of neural tube defects. However, currently available data do not support its preventive effect on congenital malformations that occur under the influence of valproic acid.

Continuous (including in the third trimester of pregnancy) special prenatal diagnostics should be carried out to identify possible malformations of the neural tube or other malformations of the fetus, including a detailed ultrasound examination.

Before childbirth. Prior to delivery, the mother should undergo coagulation tests, in particular, the determination of platelet count, fibrinogen concentration and clotting time (APTT).

risk for newborns. It was reported about the development of isolated cases of hemorrhagic syndrome in newborns whose mothers took valproic acid during pregnancy. This hemorrhagic syndrome is associated with thrombocytopenia, hypofibrinogenemia, and/or a decrease in other blood clotting factors. Afibrinogenemia has also been reported, which could be fatal. This hemorrhagic syndrome should be distinguished from vitamin K deficiency caused by phenobarbital and other inducers of microsomal liver enzymes.

Therefore, in newborns whose mothers received treatment with valproic acid during pregnancy, coagulation tests should be performed (determine the number of platelets in peripheral blood, plasma fibrinogen concentration, blood clotting factors and a coagulogram).

Cases of hypoglycemia have been reported in newborns whose mothers took valproic acid in the third trimester of pregnancy.

There have been reports of cases of hypothyroidism in newborns whose mothers took valproic acid during pregnancy.

In newborns whose mothers took valproic acid in the third trimester of pregnancy, a withdrawal syndrome may occur (in particular, the appearance of agitation, irritability, hyperreflexia, trembling, hyperkinesia, muscle tone disorders, tremors, convulsions and difficulty feeding).

Fertility

In connection with the possibility of developing dysmenorrhea, amenorrhea, polycystic ovaries, an increase in the concentration of testosterone in the blood, a decrease in fertility in women is possible. In men, valproic acid can decrease sperm motility and impair fertility. These fertility disorders have been found to be reversible after discontinuation of treatment.

breastfeeding period

Excretion of valproic acid in breast milk is low, its concentration in milk is 1-10% of its concentration in blood serum.

There are limited clinical data on the use of valproic acid during breastfeeding, and therefore the use of the drug during this period is not recommended.

Based on literature data and little clinical experience, breastfeeding with monotherapy with Depakine Chronosphere ™ can be considered, but the side effect profile of the drug, especially the hematological disorders it causes, should be taken into account.

Application for violations of liver function

The drug is contraindicated in acute hepatitis, chronic hepatitis, in cases of severe hepatitis in the patient or in his family history, especially caused by drugs, with severe liver dysfunction.

Application for violations of kidney function

The drug should be used with caution in renal failure.

Use in children

The average daily dose for children, incl. infants (starting from 6 months of life) - 30 mg / kg.

special instructions

Before starting the use of the drug Depakine® Chronosphere™ and periodically during the first 6 months of treatment, especially in patients at risk of developing liver damage, a study of liver function should be performed.

As with most antiepileptic drugs, with the use of valproic acid, a slight increase in the activity of liver enzymes is possible, especially at the beginning of treatment, which proceeds without clinical manifestations and is transient. In these patients, a more detailed study of biological parameters, including the prothrombin index, is necessary, and dose adjustment of the drug may be required, and, if necessary, repeated clinical and laboratory examinations.

Before starting therapy or surgery, in case of spontaneous occurrence of subcutaneous hematomas or bleeding, it is recommended to determine the bleeding time, the number of formed elements in the peripheral blood, including the number of platelets).

Severe liver damage

predisposing factors. Clinical experience shows that patients at risk are patients receiving several antiepileptic drugs at the same time, children under 3 years of age with severe convulsive seizures, especially against the background of brain damage, mental retardation and / or congenital metabolic or degenerative diseases; patients simultaneously taking salicylates (because salicylates are metabolized along the same metabolic pathway as valproic acid).

In children older than 3 years, the risk of liver damage is significantly reduced and progressively decreases as the age of the patient increases. In most cases, liver damage occurs during the first 6 months of treatment, most often between 2 and 12 weeks of treatment and usually with the use of valproic acid as part of a combination antiepileptic therapy.

Symptoms suggestive of liver damage. For early diagnosis of liver damage, clinical observation of patients is mandatory. In particular, attention should be paid to the appearance of the following symptoms, which may precede the onset of jaundice, especially in patients at risk:

Non-specific symptoms, especially those of sudden onset, such as asthenia, anorexia, lethargy, drowsiness, which are sometimes accompanied by recurrent vomiting and abdominal pain;

Recurrence of seizures in patients with epilepsy.

Patients or their family members (when using the drug in children) should be warned that they should immediately report the occurrence of any of these symptoms to the attending physician. If these symptoms appear, patients should immediately undergo a clinical examination and laboratory tests of liver function tests.

Identification. Determination of liver function tests should be carried out before starting treatment and then periodically during the first 6 months of treatment. Among conventional studies, the most informative studies reflect the state of the protein-synthetic function of the liver, especially the prothrombin index. Confirmation of an abnormal prothrombin index, especially in combination with abnormalities of other laboratory parameters (a significant decrease in fibrinogen and blood coagulation factors, an increase in the concentration of bilirubin and an increase in transaminase activity), as well as the appearance of other symptoms indicating liver damage, requires discontinuation of the use drug Depakine® Chronosphere™. As a precaution, if patients were taking salicylates at the same time, their intake should also be discontinued.

Pancreatitis

There are registered rare cases of severe forms of pancreatitis in children and adults, which developed regardless of age and duration of treatment. Several cases of hemorrhagic pancreatitis have been observed with rapid progression of the disease from the first symptoms to death.

Children are at an increased risk of developing pancreatitis, with increasing age of the child, this risk decreases. Severe seizures, neurological disorders, or anticonvulsant therapy may be risk factors for developing pancreatitis. Liver failure associated with pancreatitis increases the risk of death.

Patients who develop severe abdominal pain, nausea, vomiting, and/or anorexia should be evaluated immediately. In case of confirmation of pancreatitis, in particular, with increased activity of pancreatic enzymes in the blood, the use of valproic acid should be discontinued and appropriate treatment initiated.

Suicidal thoughts and attempts

Suicidal thoughts or attempts have been reported in patients receiving antiepileptic drugs for some indications. A meta-analysis of randomized placebo-controlled trials of antiepileptic drugs also showed a small increase in the risk of suicidal thoughts and attempts by 0.19% in all patients taking antiepileptic drugs (including a 0.24% increase in this risk in patients taking antiepileptic drugs for epilepsy ), compared with their frequency in patients taking placebo. The mechanism of this effect is unknown. Therefore, patients receiving Depakine® Chronosphere™ should be constantly monitored for suicidal thoughts or attempts, and if they occur, appropriate treatment should be carried out. Patients and their caregivers are advised if the patient has suicidal thoughts or attempts to seek immediate medical attention.

Carbapenems

The simultaneous use of carbapenems is not recommended.

Patients with established or suspected mitochondrial diseases

Valproic acid can initiate or exacerbate the manifestations of the patient's mitochondrial diseases caused by mutations in mitochondrial DNA, as well as in the nuclear gene encoding the mitochondrial enzyme γ-polymerase (POLG). In particular, in patients with congenital neurometabolic syndromes caused by mutations in the gene encoding γ-polymerase (POLG); for example, in patients with Alpers-Huttenlocher syndrome, valproic acid has been associated with a higher incidence of acute liver failure and liver-related deaths. Diseases due to γ-polymerase defects may be suspected in patients with a family history of such diseases or symptoms suggestive of their presence, including unexplained encephalopathy, refractory epilepsy (focal, myoclonic), status epilepticus, mental and physical retardation, psychomotor regression, axonal sensorimotor neuropathy, myopathy, cerebellar ataxia, ophthalmoplegia or complicated migraine with visual (occipital) aura and others. In accordance with current clinical practice, testing for mutations in the γ-polymerase gene (POLG) should be performed to diagnose such diseases.

Female children and adolescents, women of childbearing potential and pregnant women

Depakine® Chronosphere™ should not be used in female children and adolescents, women of childbearing potential and pregnant women, unless alternative treatments are ineffective or not tolerated. This limitation is associated with a high risk of teratogenicity and impaired mental and physical development in children who are exposed to valproic acid in utero. The benefit / risk ratio should be carefully reassessed in the following cases: during regular review of treatment, when the girl reaches puberty and urgently, in case of planning or pregnancy in a woman taking valproic acid.

During treatment with valproic acid, women of childbearing potential should use reliable methods of contraception, and they should be informed of the risks associated with taking Depakine® Chronosphere™ during pregnancy. To help the patient understand these risks, the physician prescribing valproic acid to her should provide the patient with comprehensive information about the risks associated with taking Depakine® Chronosphere™ during pregnancy.

In particular, the physician prescribing valproic acid must ensure that the patient understands:

The nature and degree of risk when using valproic acid during pregnancy, in particular, the risk of teratogenic effects, as well as the risk of impaired mental and physical development of the child;

The need to use effective contraception;

The need for regular review of treatment;

The need to urgently consult with her doctor if she suspects that pregnancy has occurred, or when she suspects this possibility.

A woman planning a pregnancy should definitely try, if possible, to transfer to an alternative treatment before she attempts to conceive.

Treatment with valproic acid should only be continued after a physician experienced in the treatment of epilepsy and bipolar disorder has reassessed the benefit/risk ratio of treatment for it.

Children (information refers to dosage forms of the drug Depakine®, which can be taken by children under 3 years of age)

In children under the age of 3 years, if necessary, the use of the drug, it is recommended to use it in monotherapy and in the dosage form recommended for children. At the same time, before starting treatment, the ratio of the potential benefit from the use of valproic acid and the risk of liver damage and the development of pancreatitis should be weighed when using it.

In children under 3 years of age, the simultaneous use of valproic acid and salicylates should be avoided due to the risk of toxic effects on the liver.

kidney failure

It may be necessary to reduce the dose of valproic acid due to an increase in the concentration of its free fraction in the blood serum. If it is not possible to monitor plasma concentrations of valproic acid, the dose of the drug should be adjusted based on clinical observation of the patient.

Deficiency of carbamide cycle enzymes (urea cycle)

If a deficiency of urea cycle enzymes is suspected, the use of valproic acid is not recommended. Several cases of hyperammonemia with stupor or coma have been described in these patients. In these cases, metabolic studies should be performed prior to treatment with valproic acid.

In children with unexplained gastrointestinal symptoms (anorexia, vomiting, episodes of cytolysis), a history of lethargy or coma, mental retardation, or a family history of neonatal or infant death, metabolic studies should be performed prior to initiating treatment with valproic acid, in particular determination ammonemia (the presence of ammonia and its compounds in the blood) on an empty stomach and after eating.

Patients with systemic lupus erythematosus

Although it has been shown that during treatment with Depakine® Chronosphere™, violations of the immune system are extremely rare, the potential benefit of its use must be weighed against the potential risk when prescribing the drug to patients with systemic lupus erythematosus.

Weight gain

Patients should be warned of the risk of weight gain at the start of treatment, and measures should be taken, mainly dietary adjustments, to minimize this phenomenon.

Patients with diabetes

Given the possibility of adverse effects of valproic acid on the pancreas, when using the drug in patients with diabetes mellitus, blood glucose concentrations should be carefully monitored. When examining urine for the presence of ketone bodies in patients with diabetes, it is possible to obtain false positive results, because. Valproic acid is excreted by the kidneys, partly in the form of ketone bodies.

HIV-infected patients

In vitro studies have shown that valproic acid stimulates HIV replication under certain experimental conditions. The clinical significance of this fact, if any, is unknown. In addition, the significance of these data obtained in vitro studies for patients receiving maximum suppressive antiretroviral therapy has not been established. However, these data should be taken into account when interpreting the results of continuous monitoring of viral load in HIV-infected patients taking valproic acid.

Patients with pre-existing carnitine palmitoyltransferase (CPT) type II deficiency

Patients with existing type II CBT deficiency should be warned about the higher risk of developing rhabdomyolysis while taking valproic acid.

During treatment with valproic acid, alcohol is not recommended.

Other special instructions

The inert matrix of the drug Depakine® Chronosphere™ (prolonged release drug), due to the nature of its excipients, is not absorbed from the gastrointestinal tract; after the release of active substances, the inert matrix is excreted with feces.

Influence on the ability to drive vehicles and control mechanisms

Patients should be warned about the risk of drowsiness, especially in the case of combined anticonvulsant therapy or when Depakine® Chronosphere™ is combined with benzodiazepines.

Overdose

Symptoms: coma with muscular hypotension, hyporeflexia, miosis, respiratory depression, metabolic acidosis, excessive decrease in blood pressure, vascular collapse / shock. Cases of intracranial hypertension associated with cerebral edema have been described. The presence of sodium in the composition of valproic acid preparations in case of their overdose can lead to the development of hypernatremia. Symptoms may vary, and seizures have been reported with very high plasma concentrations of valproic acid. With a significant overdose, a fatal outcome is possible, but the prognosis is usually favorable.

Treatment: in the hospital - gastric lavage, which is effective for 10-12 hours after ingestion of the contents of the vial with lyophilizate or solution for intravenous administration. To reduce the absorption of valproic acid, it may be effective to take activated charcoal, incl. its introduction through a nasogastric tube. Monitoring and correction of the functional state of the cardiovascular and respiratory systems, maintenance of effective diuresis, and symptomatic therapy are required.

It is necessary to control the functions of the liver and pancreas. Respiratory depression may require mechanical ventilation.

Naloxone has been used successfully in some cases. In very severe cases of significant overdose, hemodialysis and hemoperfusion have been effective.

drug interaction

Effect of valproic acid on other drugs

Valproic acid can potentiate the action of other psychotropic drugs, such as neuroleptics, MAO inhibitors, antidepressants, benzodiazepines (with simultaneous use, careful medical supervision and, if necessary, dose adjustment is recommended).

Valproic acid does not affect the serum concentration of lithium.

Valproic acid increases the concentration of phenobarbital in plasma (due to a decrease in its hepatic metabolism), and therefore the development of a sedative effect of the latter is possible, especially in children. Therefore, careful medical monitoring of the patient during the first 15 days of combination therapy is recommended, with an immediate reduction in the dose of phenobarbital in the event of a sedative effect and, if necessary, determination of the plasma concentration of phenobarbital.

Valproic acid increases the plasma concentration of primidone, leading to an increase in its side effects (such as sedation); with prolonged treatment, these symptoms disappear. Careful clinical monitoring of the patient is recommended, especially at the beginning of combination therapy with dose adjustment of primidone if necessary.

Valproic acid reduces the total plasma concentration of phenytoin. In addition, valproic acid increases the concentration of the free fraction of phenytoin with the possibility of developing overdose symptoms (valproic acid displaces phenytoin from its association with blood plasma proteins and slows down its hepatic metabolism). Therefore, careful clinical monitoring of the patient and determination of the concentration of phenytoin and its free fraction in the blood is recommended.

With the simultaneous use of valproic acid and carbamazepine, the occurrence of clinical manifestations of carbamazepine toxicity has been reported, tk. valproic acid may potentiate the toxic effects of carbamazepine. Careful clinical monitoring of such patients is recommended, especially at the beginning of combination therapy with correction, if necessary, of the dose of carbamazepine.

Valproic acid slows down the metabolism of lamotrigine in the liver and increases T1 / 2 of lamotrigine by almost 2 times. This interaction can lead to increased toxicity of lamotrigine, in particular to the development of severe skin reactions, including toxic epidermal necrolysis. Therefore, careful clinical observation and, if necessary, dose adjustment (reduction) of lamotrigine is recommended.

Valproic acid may increase plasma concentrations of zidovudine, resulting in increased zidovudine toxicity.

Valproic acid can reduce the mean clearance of felbamate by 16%.

Valproic acid may decrease plasma concentrations of olanzapine.

Valproic acid can lead to an increase in the plasma concentration of rufinamide. This increase depends on the concentration of valproic acid in the blood. Caution should be exercised, especially in children, because. this effect is more pronounced in this population.

Valproic acid can lead to an increase in plasma concentrations of propofol. Consideration should be given to reducing the dose of propofol when co-administered with valproic acid.

Strengthening the hypotensive effect of nimodipine (for oral administration and, by extrapolation, for parenteral administration) due to an increase in its plasma concentration (inhibition of the metabolism of nimodipine by valproic acid).

Co-administration of temozolomide with valproic acid results in a mild but statistically significant decrease in the clearance of temozolomide.

Effect of other drugs on valproic acid

Antiepileptic drugs that can induce microsomal liver enzymes (including phenytoin, phenobarbital, carbamazepine) reduce the plasma concentration of valproic acid. In the case of combination therapy, the dose of valproic acid should be adjusted depending on the clinical response and the concentration of valproic acid in the blood.

The concentration of metabolites of valproic acid in the blood serum may be increased if it is used simultaneously with phenytoin or phenobarbital. Therefore, the condition of patients receiving these combinations should be carefully monitored for signs and symptoms of hyperammonemia, tk. some metabolites of valproic acid can inhibit the enzymes of the urea cycle (urea cycle).

With the combination of felbamate and valproic acid, the clearance of valproic acid is reduced by 22-50% and, accordingly, the plasma concentration of valproic acid increases. The plasma concentration of valproic acid should be monitored.

Mefloquine accelerates the metabolism of valproic acid and is itself capable of causing convulsions, therefore, with their simultaneous use, the development of an epileptic seizure is possible.

With the simultaneous use of valproic acid and preparations of St. John's wort, a decrease in the anticonvulsant effectiveness of valproic acid is possible.

In the case of simultaneous use of valproic acid and drugs that have a high and strong connection with blood plasma proteins (acetylsalicylic acid), it is possible to increase the concentration of the free fraction of valproic acid.

With the simultaneous use of valproic acid and indirect anticoagulants (warfarin and other coumarin derivatives), careful monitoring of INR and prothrombin index is required.

The concentration of valproic acid in the blood plasma may increase with the simultaneous use of cimetidine or erythromycin (as a result of slowing down its hepatic metabolism).

Decrease in the concentration of valproic acid in the blood when it is used simultaneously with carbapenems (panipenem, meropenem, imipenem): for 2 days of joint therapy, a 60-100% decrease in the concentration of valproic acid in the blood plasma was observed, which was sometimes combined with the occurrence of seizures. The simultaneous use of carbapenems in patients with a selected dose of valproic acid should be avoided due to their ability to quickly and intensively reduce the concentration of valproic acid in plasma. If treatment with carbapenems cannot be avoided, blood levels of valproic acid should be closely monitored during and after carbapenem treatment.

Rifampicin can reduce the concentration of valproic acid in the blood, which leads to the loss of the therapeutic effect of valproic acid. Therefore, it may be necessary to increase the dose of valproic acid while using rifampicin and after its withdrawal.

Protease inhibitors, such as lopinavir, ritonavir, reduce the plasma concentration of valproic acid while using it.

Colestyramine can lead to a decrease in plasma concentrations of valproic acid when used simultaneously with it.

Other interaction

The simultaneous use of valproic acid and topiramate or acetazolamide was accompanied by encephalopathy and / or hyperammonemia. Patients receiving these combinations need careful medical supervision for the development of symptoms of hyperammoniemic encephalopathy.

The simultaneous use of valproic acid and quetiapine may increase the risk of developing neutropenia / leukopenia.

Valproic acid does not have the ability to induce liver enzymes and, as a result, valproic acid does not reduce the effectiveness of estrogen-progestogen drugs in women using hormonal contraception.

When taking ethanol and other potentially hepatotoxic drugs simultaneously with valproic acid, it is possible to increase the hepatotoxic effect of valproic acid.

The simultaneous use of clonazepam with valproic acid can lead in isolated cases to an increase in the severity of the absence status.

With the simultaneous use of drugs with a myelotoxic effect, with valproic acid, the risk of inhibition of bone marrow hematopoiesis increases.

Terms and conditions of storage

The drug should be stored out of the reach of children, at a temperature not exceeding 25°C. Do not refrigerate or freeze.
Shelf life - 2 years.

Terms of dispensing from pharmacies

The drug is dispensed by prescription.

Registration certificate holder:

SANOFI-AVENTIS FRANCE (France)

All information is presented for informational purposes and is not a reason for self-prescription or replacement of the drug.

Anticonvulsants - valproates.

Composition Depakine

The active substance is Valproic acid.

Manufacturers

Sanofi Winthrop Industry (France)

pharmachologic effect

Antiepileptic, muscle relaxant, sedative.

By inhibiting GABA transferase, it increases the content of gamma-aminobutyric acid in the central nervous system, which causes a decrease in the excitability threshold and the level of convulsive readiness of the motor areas of the brain.

When taken orally, it dissociates to valproate ion, which is absorbed into the blood plasma.

Food reduces the rate of absorption.

Metabolized in the liver.

Metabolites and conjugates are excreted by the kidneys.

A small amount of valproic acid is excreted in milk.

Side effects of Depakine

Nausea, vomiting, diarrhea, stomach pain, anorexia or increased appetite, abnormal liver function, drowsiness, tremor, paresthesia, confusion, peripheral edema, bleeding, leukopenia, thrombocytopenia.

With prolonged use - temporary hair loss.

Indications for use

Various forms of generalized seizures:

small (absences), large (convulsive) and polymorphic;
used for focal seizures, children's tics.

Contraindications Depakine

Hypersensitivity, incl. "familial" (death of close relatives while taking valproic acid), liver and pancreas diseases (in some patients, a significant decrease in liver metabolism is possible), hemorrhagic diathesis, pregnancy (I trimester), breastfeeding.

Application restrictions.

Children's age (simultaneous administration of several anticonvulsants), bone marrow aplasia, pregnancy (late terms).

Overdose

No data.

Interaction

The effect is enhanced by other anticonvulsants, sedatives and hypnotics.

Dyspeptic disorders develop less frequently against the background of antispasmodics and enveloping agents.

Alcohol and other hepatotoxic drugs increase the likelihood of liver damage, anticoagulants or acetylsalicylic acid increase the risk of bleeding.