Depakine Chronosphere

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Depakine Chronosphere: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Price in pharmacies

Latin name: Depakine chronosphere

ATX code: N03AG01

Active ingredient: valproic acid (valproic acid)

Producer: Sanofi-Winthrop Industry (France)

Description and photo update: 2018-27-11

Prices in pharmacies: from 415 rubles.

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Depakine Chronosphere Extended Release Granules 250 mg

Depakine Chronosphere is an antiepileptic drug.

Release form and composition

Dosage form - granules with prolonged release: waxy, slightly yellowish or almost white, easily free-flowing, not forming agglomerates [100, 250, 500, 750 and 1000 mg in sachets from a three-layer complex (paper + aluminum + ionomer resin), in a cardboard box of 30 or 50 sachets and instructions for the use of Depakine Chronosphere].

Active substances:

Depakine Chronosphere 100 mg: sodium valproate - 66.66 mg, valproic acid - 29.03 mg (in terms of sodium valproate, a total of 100 mg);
Depakine Chronosphere 250 mg: sodium valproate - 166.76 mg, valproic acid - 72.61 mg (in terms of sodium valproate, a total of 250 mg);
Depakine Chronosphere 500 mg: sodium valproate - 333.3 mg, valproic acid - 145.14 mg (in terms of sodium valproate, a total of 500 mg);
Depakine Chronosphere 750 mg: sodium valproate - 500.06 mg, valproic acid - 217.75 mg (in terms of sodium valproate, 750 mg in total);
Depakine Chronosphere 1000 mg: sodium valproate - 666.6 mg, valproic acid - 290.27 mg (in terms of sodium valproate, a total of 1000 mg).

Auxiliary components (in granules 100/250/500/750/1000 mg): solid paraffin - 101.26 / 253.32 / 506.31 / 759.64 / 1012.63 mg, glycerol dibegenate - 106.05 / 265, 3 / 530.25 / 795.55 / 1060.5 mg, colloidal aqueous silicon dioxide (added by spraying after the melt cooling process) - 0.7% of the amount of four other components, 0.56% is absorbed on the granules.

Pharmacological properties

Pharmacodynamics

Depakine Chronosphere is an antiepileptic agent with a sedative and central muscle relaxant effect.

It exhibits anticonvulsant activity in various types of epilepsy.

The main mechanism of action of the drug is associated, presumably, with the effect of valproic acid on the GABAergic system, namely, with an increase in GABA in the central nervous system and the activation of GABAergic transmission.

Pharmacokinetics

After oral administration, the bioavailability of valproic acid is almost 100%. Chronosphere does not affect the pharmacokinetics of Depakine at the same time.

The maximum plasma concentration (C _max) of the drug is observed approximately 7 hours after taking Depakine Chronosphere.

Compared to valproic acid in the form of enteric-coated tablets, granules in equivalent doses are characterized by a longer absorption, similar bioavailability, as well as a more linear correlation between doses and the concentration of the drug in blood plasma (total concentration and concentration of the free fraction). The total C _max and C _{max of the} free fraction are lower (by about 25%), but there is a relatively more stable plateau phase of plasma concentrations - from 4 to 14 hours after administration. The level of fluctuations in plasma concentrations when taking granules in comparison with enteric-coated tablets is reduced by 2 times, as a result of which the drug is more evenly distributed in the tissues of the body during the day.

The equilibrium concentration of valproic acid in the blood serum during the course of administration of Depakine Chronosphere is achieved within 3-14 days.

To achieve a therapeutic effect, serum concentrations of the drug from 40 to 100 mg / l are usually required. At concentrations above 100 mg / l, an increase in the frequency and severity of side effects is expected, up to the development of intoxication.

The volume of distribution of valproic acid depends on age, on average is 0.13-0.23 l / kg, in young people - 0.13-0.19 l / kg.

The drug is characterized by a high binding to plasma proteins (mainly albumin) - 90–95%, which is dose-dependent and saturable. Plasma protein binding is reduced in the elderly and patients with renal / hepatic impairment. In patients with severe renal failure, the concentration of the free (therapeutically active) fraction of valproic acid may increase to 8.5–20%. With concomitant hypoproteinemia, the total concentration of valproic acid (free + plasma protein-bound fraction) may not change, but it may decrease due to an increase in the metabolism of the free fraction (not bound to blood plasma proteins).

The drug enters the brain and cerebrospinal fluid. The concentration in the cerebrospinal fluid is about 10% of the serum level, that is, approximately the same as the concentration of the free fraction of valproic acid in the blood serum.

The drug passes into breast milk. In women whose serum has reached an equilibrium concentration of valproic acid, up to 10% of the serum concentration is found in breast milk.

Valproic acid is metabolized in the liver by glucuronidation, as well as omega, omega ₁ - and beta oxidation, resulting in the formation of a large number of metabolites (more than 20 have been found). Metabolites resulting from omega-oxidation are hepatotoxic.

Valproic acid does not induce enzymes of the cytochrome P _{450 system}, since it does not affect the degree of either its own metabolism or the metabolism of other substances (indirect anticoagulants, progestogens, estrogens, etc.).

The drug is excreted from the body mainly by the kidneys after conjugation with glucuronic acid and beta-oxidation.

If Depakine Chronosphere is used as a monopreparation, the half-life (T _½) of valproic acid is 12-17 hours. When used in combination with antiepileptic drugs that induce microsomal liver enzymes (for example, phenobarbital, carbamazepine, phenytoin, primidone), plasma clearance valproic acid and its half-life decreases, the magnitude of these changes depends on the degree of induction of microsomal liver enzymes by other antiepileptic drugs.

In children older than 2 months, T _{½ is} approximately similar to that in adults.

In patients with concomitant liver diseases, the T _{½ of the} drug increases. In case of an overdose, an increase in T _½ to 30 hours is possible. With the help of hemodialysis, only the free fraction of valproic acid in the blood is excreted (5–10%).

With an increase in the volume of distribution of valproic acid in the third trimester of pregnancy, its hepatic and renal clearance increase. Even when taking Depakine Chronosphere at a constant dose, this may be accompanied by a decrease in serum valproic acid concentrations. Also, in pregnant women, it is possible to change the connection of the drug with plasma proteins, as a result of which the serum concentration of the free therapeutically active fraction may increase.

Indications for use

General indications for adults and children from 6 months of age:

partial epileptic seizures, including those with secondary generalization;
generalized epileptic seizures (atonic, myoclonic, tonic, clonic, tonic-clonic, absences, Lennox-Gastaut syndrome).

Additional indications:

adults: treatment and prevention of bipolar disorder;
children over 6 months of age: high fever - to prevent the development of seizures (in cases where such prevention is necessary).

Depakine Chronosphere is used either as a monopreparation or as part of combination therapy simultaneously with other antiepileptic drugs.

Contraindications

thrombocytopenia, hemorrhagic diathesis;
severe dysfunction of the liver or pancreas;
hepatic porphyria;
acute or chronic hepatitis;
a history of severe liver disease (especially drug hepatitis) in the patient and his close blood relatives;
severe liver damage that developed with the use of valproic acid and led to death, in close blood relatives of the patient;
established violations of the urea cycle (urea cycle);
diagnosed mitochondrial diseases caused by mutations in the nuclear gene that encodes the mitochondrial enzyme γ-polymerase (POLG), for example, Alpers-Huttenlocher syndrome;
suspicion of diseases caused by POLG defects in children under 2 years of age;
simultaneous use of St. John's wort or mefloquine;
children's age up to 6 months;
individual hypersensitivity to valproic acid, sodium valproate, valpromide, seminatrium valproate or any of the auxiliary components of the drug.

Depakine Chronosphere should be used with extreme caution in the following cases:

congenital fermentopathies;
hypoproteinemia;
oppression of bone marrow hematopoiesis (thrombocytopenia, leukopenia, anemia);
history of liver / pancreas disease;
renal failure;
type II carnitine palmitoyltransferase (CBT) deficiency (increased risk of rhabdomyolysis);
pregnancy;
simultaneous administration of several anticonvulsants (due to an increased risk of liver damage);
concomitant use of drugs that can lower the seizure threshold or provoke seizures, such as selective serotonin reuptake inhibitors (SSRIs), butyrophenone derivatives, phenothiazine derivatives, tricyclic antidepressants, tramadol, bupropion, chloroquine (due to the risk of seizures);
the combined use of monoamine oxidase (MAO) inhibitors, benzodiazepines, neuroleptics, antidepressants (effects may be potentiated);
simultaneous use of acetazolamide or topiramate (there is a risk of developing encephalopathy);
joint administration of carbamazepine (its toxic effects may increase, a decrease in the plasma concentration of valproic acid is possible);
the combined use of the following drugs: indirect anticoagulants, phenobarbital, phenytoin, primidone, felbamate, cimetidine, zidovudine, lamotrigine, nimodipine, erythromycin, rifampicin, carbapenems, colestyramine, protease inhibitors (lopinavir, acetyl-ritonavirinamidinamidine acid) …

Depakine Chronosphere, instructions for use: method and dosage

Depakine Chronosphere should be taken orally. Granules are especially suitable for children and adults who have trouble swallowing.

Depakine Chronosphere 100 mg sachets are prescribed only for children, Depakine Chronosphere 1000 mg - only for adults.

The granules should be poured onto the surface of cold (no higher than room temperature) soft food or drink (for example, fruit puree, yoghurt or orange juice). Do not take the drug with hot meals and drinks (soups, tea, coffee, etc.). When taking the drug with liquids, it should be borne in mind that the granules can stick to the glass, therefore, after taking it, it is recommended to rinse the glass with a small amount of drinking water and drink it.

Food / drink with added granules cannot be stored. It should be swallowed without chewing.

The granules should not be poured into a baby bottle with a nipple as they can clog the opening of the nipple.

Dosage regimen

The dose of Depakine Chronosphere is always calculated by the amount of sodium valproate.

For the treatment of manic episodes in bipolar disorders, the dose of Depakine Chronosphere is selected individually (taking into account the age and body weight of the patient) and monitored by the attending physician. At the beginning of therapy, the recommended daily dose is 20 mg / kg. If possible, it should be rapidly increased to the minimum dose that will provide the desired therapeutic effect.

The maintenance daily dose for bipolar disorders can vary within 1000–2000 mg, it is selected individually depending on the patient's clinical response to therapy.

For the prevention of manic conditions, it is recommended to use the drug in the minimum effective dose, which the doctor selects individually for each patient.

In monotherapy for epilepsy, Depakine Chronosphere is usually prescribed at an initial dose of 5-10 mg / kg with a gradual increase - by 5 mg / kg every 4-7 days until the optimal dose is reached to prevent the development of epileptic seizures.

Average daily doses for epilepsy treatment:

children under 14 years old - 30 mg / kg;
adolescents 14-18 years old - 25 mg / kg;
adults, including elderly patients (weighing> 60 kg) - 20 mg / kg.

Thus, the following daily doses are recommended:

children 6-12 months (body weight 7.5-10 kg) - 150-300 mg;
children 1-3 years old (10-15 kg) - 300-450 mg;
children 3-6 years old (15-25 kg) - 450-750 mg;
children 7-14 years old (25-40 kg) - 750-1200 mg;
adolescents from 14 years old (40-60 kg) - 1000-1500 mg;
adults (from 60 kg) - 1200-2100 mg.

If necessary, under the control of the concentration of valproic acid in the blood, the average daily dose is increased.

The full therapeutic effect of Depakine Chronosphere in some cases develops within 4–6 weeks, therefore, earlier than this period, the daily dose should not be increased above the recommended average. In addition to the patient's age and body weight, a wide range of individual sensitivity to valproic acid should also be considered.

A clear dependence of the therapeutic effect on the daily dose and the concentration of valproic acid in the blood serum has not been established, therefore, the doctor should select the optimal dose mainly based on the patient's clinical response. Determination of serum valproic acid concentration can be used in addition to clinical observation in cases where epilepsy is uncontrollable or side effects are suspected. Doses at which serum valproic acid levels are 40–100 mg / l are effective. At concentrations above 100 mg / l, side effects may increase, therefore, if it is necessary to increase doses to achieve higher serum concentrations of the drug, the expected benefits and possible risks of intoxication should be carefully evaluated.

The serum concentration of valproic acid is determined before the first administration of Depakine Chronosphere on this day, it should not exceed 100 mg / ml.

Special cases

When transferring a patient to Depakine Chronosphere from other dosage forms of the Depakine line, which made it possible to control epilepsy well, the same dose of valproic acid should be maintained.

Caution should be exercised when transferring a patient to Depakine Chronosphere from other antiepileptic drugs. The drug should be changed gradually, reaching the optimal dose over about 2 weeks. In this case, the dose of the previously used antiepileptic agent (especially phenobarbital) is reduced immediately, but the complete cancellation is carried out gradually. These drugs can reversibly induce microsomal enzymes in the liver, therefore, within 4-6 weeks after their complete cancellation, the level of valproic acid in the blood should be monitored and, if necessary, the dose should be reduced.

If it becomes necessary to add other antiepileptic drugs to Depakine Chronosphere, this should be done gradually.

Treatment of children, adolescent girls, women of childbearing age and pregnant women should begin under the supervision of a specialist who has experience in the treatment of epilepsy and bipolar disorders. Depakine Chronosphere is prescribed only if other therapies are ineffective or poorly tolerated. With regular follow-up, the physician should re-evaluate the balance of benefits and risks. For these categories of patients, Depakine Chronosphere is preferably used as a monopreparation in the lowest effective doses. During pregnancy, the daily dose is divided into 2 doses.

Side effects

Classification of the frequency of adverse reactions: very often - ≥ 10%, often - from ≥ 1 to <10%, infrequently - from ≥ 0.1 to <1%, rarely - from ≥ 0.01 to <0.1%, very rarely - <0.01%, unknown frequency - it is not possible to set the frequency from the available data.

Possible side effects of Depakine Chronosphere:

laboratory and instrumental data: rarely - biotin deficiency or biotinidase deficiency;
congenital, hereditary and genetic disorders: teratogenic risk;
on the part of the skin and subcutaneous tissues: often - violations of the nails and nail bed, reversible / or dose-dependent pathological hair loss (including alopecia on the background of developed hypothyroidism, androgenic alopecia on the background of developed polycystic ovary disease, hyperandrogenism), hypersensitivity reactions; infrequently - skin rashes, hair disorders (changes in color and normal structure, abnormal growth, for example, the appearance of curl in patients with straight hair, or, on the contrary, the disappearance of existing waviness), angioedema; rarely - erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash syndrome with eosinophilia and systemic symptoms (DRESS syndrome);
from the digestive system: very often - nausea; often - stomatitis, changes in the gums (mainly hyperplasia), vomiting, diarrhea, epigastric pain (frequent side effects usually occur at the beginning of treatment, most often go away on their own and do not require discontinuation of therapy; the risk of their development can be reduced by taking granules with or after meals food intake); infrequently - pancreatitis, sometimes fatal (may occur in the first 6 months of taking Depakine Chronosphere; in case of acute abdominal pain, serum amylase activity should be monitored); frequency unknown - increased appetite, anorexia, abdominal cramps;
on the part of metabolism and nutrition: often - an increase in body weight (body weight should be carefully monitored, since its increase is a risk factor for the development of polycystic ovary syndrome), hyponatremia; rarely - hyperammonemia (from isolated and moderate to accompanied by neurological symptoms, for example, vomiting, encephalopathy, ataxia and other symptoms, which requires the abolition of valproic acid), obesity;
from the endocrine system: infrequently - hyperandrogenism (acne, virilization, hirsutism, increased concentrations of androgens in the blood and / or male-pattern alopecia), syndrome of inappropriate antidiuretic hormone secretion; rarely - hypothyroidism;
on the part of the blood and lymphatic system: often - anemia, thrombocytopenia; infrequently - neutropenia, leukopenia and pancytopenia, including those with bone marrow depression; rarely - a deviation from the norm of blood coagulation indicators, a decrease in the content of blood coagulation factors, disorders of bone marrow hematopoiesis, including isolated aplasia / hypoplasia of erythrocytes, macrocytosis, macrocytic anemia, agranulocytosis (in case of spontaneous ecchymosis and bleeding, Depakin Chronosphere should be canceled and examination of the patient);
from the kidneys and urinary tract: infrequently - renal failure; rarely - enuresis, reversible Fanconi syndrome, tubulointerstitial nephritis;
from the side of the vessels: often - bleeding and hemorrhage; infrequently - vasculitis;
on the part of the musculoskeletal system and connective tissue: infrequently, with long-term use of drugs of the Depakine line - a decrease in bone mineral density, fractures, osteoporosis; rarely - rhabdomyolysis, systemic lupus erythematosus;
from the respiratory system: infrequently - pleural effusion;
from the liver and biliary tract: often - liver damage, liver failure, in exceptional cases - fatal;
from the genitals and mammary glands: often - dysmenorrhea; infrequently - amenorrhea; rarely - polycystic ovary disease, male infertility; frequency unknown - breast enlargement, irregular menstruation, galactorrhea;
from the organs of hearing and vision: often - reversible and irreversible deafness; frequency unknown - diplopia;
benign, malignant and indeterminate tumors: rarely - myelodysplastic syndrome;
from the nervous system: very often - tremor; often - dizziness, headache, memory impairment, drowsiness, extrapyramidal disorders, nystagmus, stupor *, convulsions *; infrequently - paresthesia, ataxia, reversible parkinsonism, an increase in the frequency and severity of seizures (including the development of status epilepticus) or the appearance of new types of seizures, encephalopathy *, coma *, lethargy *; rarely - cognitive disorders, reversible dementia, combined with reversible brain atrophy; frequency unknown - sedation;
on the part of the psyche: often - depression (with the simultaneous use of other anticonvulsants), hallucinations, confusion, agitation **, aggressiveness **, impaired attention **; rarely - depression (with valproic acid monotherapy), learning disabilities **, psychomotor hyperactivity **, behavioral disorders **.

* These adverse reactions mainly occurred with the use of Depakine Chronosphere as part of a combination therapy, especially with the simultaneous use of topiramate or phenobarbital, as well as after a sharp increase in the dose of valproic acid. Stupor and lethargy led to transient encephalopathy / coma, were isolated or combined with an increase in seizures during therapy, decreased with a decrease in the dose of the drug or its cancellation.

** These adverse reactions were observed mainly in children.

Overdose

In the case of an acute massive overdose, coma occurs with hyporeflexia, muscle hypotonia, metabolic acidosis, respiratory depression, miosis, an excessive decrease in blood pressure, and vascular collapse / shock. Due to the presence of sodium in the composition of Depakine Chronosphere, hypernatremia may develop in case of an overdose. Cases of intracranial hypertension due to cerebral edema have been described.

Symptoms of a valproic acid overdose may vary. Seizures have been reported at very high plasma concentrations of the drug.

The prognosis is usually favorable, but with a massive overdose, a lethal outcome is possible.

In case of a significant excess of the dose of Depakine Chronosphere, urgent hospitalization of the patient is indicated. Emergency care includes gastric lavage (if no more than 12 hours have passed since the reception), intake or administration of activated carbon through a nasogastric tube to reduce the absorption of valproic acid. Maintenance of effective diuresis, careful monitoring of the functions of the liver and pancreas, respiratory and cardiovascular systems is required. If respiratory depression occurs, artificial ventilation may be required. In very severe cases of massive overdose, hemodialysis and hemoperfusion have been effective. Naloxone has been used successfully in some cases.

special instructions

Before the appointment of Depakine Chronosphere and regularly in the first six months of its use, liver function should be monitored, especially in patients at risk of damage to this organ.

In case of an increase in the activity of liver enzymes, it is necessary to conduct a detailed study of the biological indicator, including the prothrombin index, if necessary, adjust the dose of the drug, and, if necessary, conduct a repeated clinical and laboratory examination.

In case of spontaneous occurrence of subcutaneous hematomas or bleeding, before starting treatment or surgery, it is recommended to conduct an examination, including determining the time of bleeding and the number of formed elements in the blood (including platelets).

Predisposing factors for the development of severe liver damage against the background of the use of valproic acid:

children under 3 years of age with severe convulsive seizures, especially against the background of mental retardation, brain damage, congenital metabolic / degenerative diseases;
simultaneous use of several antiepileptic drugs;
combined intake of salicylates.

Signs indicating possible liver damage:

resumption of seizures in patients with epilepsy;
nonspecific symptoms (especially those that started suddenly): asthenia, drowsiness, lethargy, anorexia, sometimes accompanied by abdominal pain and repeated vomiting.

Patients and parents whose children receive Depakine Chronosphere should be warned about the need for immediate medical attention if these symptoms occur. An immediate clinical examination and laboratory study of liver function indicators are shown.

There are known cases of severe forms of pancreatitis, including hemorrhagic pancreatitis with rapid progression to death. Children are at increased risk. Risk factors include neurologic disorders, severe seizures, and anticonvulsant therapy. If you experience severe abdominal pain, see your doctor immediately. If pancreatitis is confirmed, Depakine Chronosphere is canceled and appropriate treatment is started.

There have been reports of suicidal intentions in patients receiving anticonvulsants for some indications. The mechanism of this action has not been established. Patients are advised to immediately consult a doctor in case of suicidal thoughts. Parents, caregivers, and family members are encouraged to monitor patients' behavior for mood changes.

Valproic acid can cause or worsen the course of existing mitochondrial diseases (diseases caused by mutations in mitochondrial DNA and the nucleus of the gene that codes for the mitochondrial enzyme POLG). Cases of acute liver failure, including fatal ones, have been reported. Symptoms suggesting the presence of mitochondrial disease: unexplained encephalopathy, mental and physical retardation, status epilepticus, refractory epilepsy (focal, myoclonic), axonal sensorimotor neuropathy, psychomotor regression, cerebellar ataxia, myopathy, or ophturate. Such diseases may be suspected in patients with family history of such diseases. In these cases, diagnostic tests for mutations in the POLG gene are required.

Valproic acid, like other antiepileptic drugs, instead of improving in some patients, may cause new types of seizures or a reversible increase in the frequency and severity of seizures, including the development of status epilepticus. If the seizures intensify, an urgent need to see a doctor.

Depakine Chronosphere is contraindicated for use in case of suspected enzyme deficiency of the urea cycle, which is due to the risk of hyperammonemia with stupor or coma. Metabolic studies should be performed prior to taking the drug. Before prescribing an anticonvulsant, fasting ammonia after eating is required in children with unexplained gastrointestinal symptoms (cases of cytolysis, anorexia, vomiting), a history of coma or lethargy, mental retardation, and a family history of death of a newborn or child.

Dysfunctions of the immune system during the period of taking Depakine Chronosphere are extremely rare, however, patients with systemic lupus erythematosus can be prescribed the drug after assessing the benefits / risks.

Valproic acid has an adverse effect on the pancreas, therefore, during the period of therapy, the concentration of glucose in the blood in patients with diabetes should be carefully monitored. In patients with this disease, when examining urine for the presence of ketone bodies, false-positive results may be obtained, since the drug is partially excreted in the form of ketone bodies.

In vitro studies have shown that, under certain experimental conditions, valproic acid is able to stimulate the replication of the human immunodeficiency virus (HIV). Whether this phenomenon has clinical significance has not been established. It is also unknown whether these findings are relevant to patients receiving maximal suppressive antiretroviral therapy. However, in HIV-infected patients, if they are taking Depakine Chronosphere, this information should be taken into account when interpreting the results of continuous monitoring of viral load.

For the period of treatment, you should stop taking alcoholic beverages.

Depakine Chronosphere should not be used in female children and adolescents, in women of childbearing age and pregnant women, except in cases of extreme necessity when other types of therapy have been ineffective or poorly tolerated. This limitation is due to the high risk of teratogenic effect, the occurrence of physical and mental development disorders in children who were exposed to the drug in utero. The clinician should reevaluate the benefit / risk ratio when a girl reaches puberty and when she regularly reviews treatment.

Influence on the ability to drive vehicles and complex mechanisms

Due to the risk of drowsiness when driving and working with complex mechanisms, caution should be exercised during the treatment period, especially with the simultaneous use of other drugs.

Application during pregnancy and lactation

Depakine Chronosphere should not be administered to pregnant women and women of reproductive age unless absolutely necessary. The use of the drug is possible, but only in cases where alternative methods of treatment were ineffective or poorly tolerated, since the development of status epilepticus with hypoxia and generalized tonic-clonic epileptic seizures can be dangerous (with a risk of death) for both the mother and the fetus …

There is evidence that children whose mothers took valproic acid during pregnancy have an increased risk of developing the following pathologies and disorders: congenital defects of the neural tube, hypospadias, malformations of the limbs and the cardiovascular system, craniofacial deformities, and other multiple malformations affecting various organ systems, hemorrhagic syndrome, hypothyroidism, delayed physical and mental development (mastering the skills of walking, the development of speech, memory and intellectual abilities), autism spectrum disorders, including childhood autism, attention deficit / hyperactivity disorder.

Risk factors for the formation of fetal malformations are the excess of the daily dose of valproic acid (more than 1000 mg) and its combination with other anticonvulsants.

Women of reproductive age should use reliable methods of contraception during the entire treatment period. The doctor should educate them about the serious risks of taking valproic acid during pregnancy. Before prescribing Depakine Chronosphere, a medical specialist should make sure that the patient understands the nature and magnitude of the danger of taking the drug during pregnancy, the importance of using effective contraception and regularly reviewing the therapy regimen, as well as the need for urgent medical advice if pregnancy is suspected.

If you are planning a pregnancy, you should consult with your doctor. If possible, the woman should be transferred to alternative therapy before attempting conception.

Continuation of valproic acid is possible only after a medical professional with experience in the treatment of epilepsy and bipolar disorders overestimates the benefit / risk ratio for the patient.

Fertility

While taking valproic acid, polycystic ovary disease, amenorrhea or dysmenorrhea may develop, as well as an increase in testosterone concentration in the blood. In this regard, a woman's fertility may decrease. In men, Depakine Chronosphere can impair fertility and reduce sperm motility. These disorders are reversible after discontinuation of therapy.

Breast-feeding

The concentration of valproic acid in breast milk is 1–10% of its serum level.

Clinical data on the use of the drug during lactation are very limited, therefore Depakine Chronosphere is not recommended for use during this period.

Considering the available literature data and little clinical experience, the issue of maintaining breastfeeding in the case of monotherapy with an anticonvulsant drug can be considered. However, it is necessary to consider the profile of its side effects, especially hematological disorders.

Pediatric use

Depakine Chronosphere is used in the treatment of children from the age of 6 months. However, in children under 3 years of age, it is recommended to use it in monotherapy and only after assessing the balance between the benefits and risks of liver damage and the development of pancreatitis.

Children under 3 years of age should not be given valproic acid concomitantly with salicylates, as this combination increases the risk of liver toxicity.

With impaired renal function

In renal failure and / or hypoproteinemia, in order to avoid an error in the selection of the dose, one should focus primarily on the clinical picture, and not on the total content of valproic acid in the blood serum (free fraction + plasma protein-bound fraction).

It should be borne in mind that in patients of this group, the serum concentration of the free fraction of valproic acid may increase, which requires a decrease in the dose of the drug. If it is not possible to monitor the plasma concentrations of valproic acid, the dose of Depakine Chronosphere should be adjusted based on clinical observation of the patient.

For violations of liver function

Depakine Chronosphere is contraindicated in the following cases: severe liver dysfunction, acute and chronic hepatitis, hepatic porphyria, severe liver disease (especially drug hepatitis) in the patient's history or his close blood relatives, as well as severe liver damage that developed with the use of valproic acid and led to death, in close blood relatives of the patient.

Use in the elderly

Changes in the pharmacokinetic parameters of valproic acid in the elderly are of limited clinical significance. Nevertheless, the doctor must select the dose of Depakine Chronosphere individually, taking into account the patient's response to therapy.

Drug interactions

Effect of other drugs on valproic acid:

drugs with a high and strong bond with plasma proteins (for example, acetylsalicylic acid): the free fraction of valproic acid may increase;
indirect anticoagulants (warfarin and other coumarin derivatives): it is possible to increase the activity of hepatic enzymes (it is necessary to carefully monitor the prothrombin index);
antiepileptic drugs that induce liver microsomal enzymes (including phenobarbital, phenytoin, carbamazepine): the plasma concentration of valproic acid decreases; phenobarbital and phenytoin can increase the serum concentration of valproic acid metabolites (with simultaneous use, special care should be taken to control the plasma concentrations of drugs);
cholestyramine: the concentration of valproic acid in the blood plasma decreases;
St. John's wort preparations: decreases the anticonvulsant activity of Depakine Chronosphere;
felbamate: the clearance of valproic acid decreases by 22-50%, and its plasma concentrations increase;
protease inhibitors (for example, ritonavir and lopinavir), rifampicin: a decrease in the concentration of valproic acid and a decrease in its therapeutic effect is possible;
erythromycin, cimetidine: an increase in the concentration of valproic acid is possible;
mefloquine: the metabolism of valproic acid is accelerated, seizures may develop under the action of mefloquine;
carbapenems (meropenem, panipenem, imipenem): the concentration of valproic acid decreases significantly, as a result of which seizures may occur (it is not recommended to use these drugs simultaneously; if the combination cannot be avoided, the level of valproic acid in the blood should be carefully monitored).

The effect of valproic acid on other drugs:

temozolomide: its clearance decreases;
nimodipine: its plasma concentration increases and the hypotensive effect increases;
antidepressants, MAO inhibitors, antipsychotics, benzodiazepines: their effects may be enhanced (dose adjustment may be required, careful medical supervision is necessary);
carbamazepine: development of its toxic effects is possible (medical supervision of patients is necessary, especially at the beginning of combination therapy, if necessary, adjustment of the carbamazepine dose);
olanzapine: its plasma concentration may decrease;
zidovudine, primidone: its plasma concentrations increase, side effects increase (control is required);
propofol: an increase in its plasma concentrations is possible (dose reduction is required);
phenytoin: its plasma concentration decreases, the concentration of the free fraction of phenytoin increases, which can lead to overdose (control is necessary);
felbamate: its average clearance values are reduced by 16%;
phenobarbital: its plasma concentrations increase, which can enhance the sedative effect, especially in children (monitoring of therapy is required, if necessary, determination of the level of the drug in the blood);
rufinamide: plasma concentrations increase (caution is needed, especially in children);
lamotrigine: its metabolism in the liver slows down, the half-life increases by almost 2 times, as a result of which toxicity increases (observation is recommended, if necessary - dose adjustment);
lithium preparations: the effect of valproic acid was not observed.

Other interactions:

myelotoxic drugs: the likelihood of inhibition of bone marrow hematopoiesis increases;
topiramate, acetazolamide: the risk of encephalopathy and / or hyperammonemia increases;
clonazepam: in isolated cases, the severity of the absence status increases;
quetiapine: possible development of neutropenia / leukopenia;
ethanol and other potentially hepatotoxic agents: the hepatotoxic effect of valproic acid may increase;
estrogen-progestogenic drugs: no effect of valproic acid was found.

Analogs

Depakine Chronosphere analogs are: Galodif, Acetazolamide, Diacarb, Maliazin, Chloracon, Benzonal, Valparin, Konvuleks, Depamid, Gabagamma, Konvalis, Relanium, Sibazon, Dipromal, Valopixim, Encorat, Tegolpulpimpat, etc.

Terms and conditions of storage

Keep out of reach of children at temperatures up to 25 ° C. Do not refrigerate or freeze.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews of Depakine Chronosphere

According to reviews, Depakine Chronosphere is a highly effective anticonvulsant agent. However, according to most patients, it can be taken only in cases of extreme necessity, when there is no alternative therapy. This is due to the high toxicity of valproic acid, which is manifested by side effects from various body systems, as well as a serious negative effect on the intrauterine development of the child.

Its disadvantages include a large list of contraindications and a fairly high cost, given the duration of treatment.

The price of Depakine Chronosphere in pharmacies

The price of Depakine Chronosphere depends on the dosage.

Approximate cost of 30 sachets:

Depakine Chronosphere 100 mg - 604-648 rubles;
Depakine Chronosphere 250 mg - 615-726 rubles;
Depakine Chronosphere 500 mg - 656-714 rubles;
Depakine Chronosphere 750 mg - 889-945 rubles;
Depakine Chronosphere 1000 mg - 1088-1226 rubles.

Depakine Chronosphere: prices in online pharmacies

Drug name

Price

Pharmacy

Depakine Chronosphere 250 mg prolonged release granules 30 pcs.

415 RUB

Buy

Depakine Chronosphere 100 mg prolonged-release granules 30 pcs.

440 RUB

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Depakine Chronosphere 500 mg prolonged release granules 30 pcs.

RUB 519

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Depakine Chronosphere granules for internal approx. with prolonged release. 100mg 30 pcs.

RUB 530

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Depakine Chronosphere granules for internal approx. with prolonged release. 500mg 30 pcs.

639 RUB

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Depakine Chronosphere 750 mg prolonged release granules 30 pcs.

RUB 799

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Depakine Chronosphere granules for internal approx. with prolonged release. 750mg 30 pcs.

822 RUB

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Depakine Chronosphere 1000 mg prolonged-release granules 30 pcs.

966 RUB

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Depakine Chronosphere granules for internal approx. with prolonged release. 1g 30 pcs.

1019 RUB

Buy

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Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!