Depakine Chrono - Instructions For Use, Reviews, Tablets 300 Mg, 500 Mg

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

Depakine Chrono

Depakine chrono: instructions for use and reviews

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

Latin name: Depakine chrono

ATX code: N03AG01

Active ingredient: sodium valproate + valproic acid (valproic acid + valproate sodium)

Producer: Sanofi-Winthrop Industrie (France)

Description and photo update: 2018-21-11

Prices in pharmacies: from 214 rubles.

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Depakine Chrono is an antiepileptic agent that has a central muscle relaxant and sedative effect.

Release form and composition

Depakine Chrono is released in the form of tablets of prolonged action, coated with: oblong, almost white, with a risk on both sides (dosage of 500 mg - 30 pieces in a polypropylene bottle, in a cardboard box 1 bottle; dosage of 300 mg - 50 pieces each. in a polypropylene bottle, in a cardboard box 2 bottles).

1 tablet contains:

• active ingredients: valproic acid - 87 and 145 mg, sodium valproate - 199.8 and 333 mg (for dosages of 300 and 500 mg, respectively);
• additional components: ethylcellulose 20 mPa.s, hydrated colloidal silicon dioxide, methylhydroxypropylcellulose 4000 mPa.s, (hypromellose), macrogol 6000, methylhydroxypropylcellulose 6 mPa.s (hypromellose), titanium dioxide, sodium saccharinate, talcrylate, 30% dispersion

Pharmacological properties

Pharmacodynamics

Depakine chrono is an anticonvulsant agent that demonstrates antiepileptic activity against the background of all types of epilepsy, and also has a normotimal effect. The main mechanism of action is probably associated with the effect of the drug on the GABA-ergic system, carried out by increasing the level of gamma-aminobutyric acid (GABA) in the central nervous system (CNS) and stimulating GABA-ergic transmission.

Pharmacokinetics

The bioavailability of the drug after oral administration reaches almost 100%.

When taking Depakine chrono tablets 500 mg in a daily dose of 1000 mg, the minimum plasma concentration (Cmin) of valproic acid is 44.7 ± 9.8 μg / ml, and the maximum (Cmax) is 81.6 ± 15.8 μg / ml, the period of reaching the maximum plasma concentration (Tmax) - 6.58 ± 2.23 hours. Stationary concentration (Css) in plasma is observed for 3-4 days of regular intake.

The average therapeutic range of serum valproic acid concentrations is 50–100 mg / l. If it is necessary to achieve a higher level of substance content, it is required to carefully assess the ratio of the expected benefit and the possible threat of the appearance of adverse reactions, especially dose-dependent ones. At concentrations of valproic acid in the blood exceeding 100 mg / l, the risk of developing disorders up to the onset of intoxication is aggravated. If the plasma level of the drug rises above 150 mg / l, a dose reduction is necessary.

The volume of distribution depends on age and, as a rule, can be 0.13–0.23 l / kg of body weight, and in young patients - 0.13–0.19 l / kg. The drug is characterized by a high (90–95%), dose-dependent and saturable bond with plasma proteins, mostly with albumin.

The active substance is found in the brain and cerebrospinal fluid. Its concentration in cerebrospinal fluid is approximately 10% of the concentration in serum. Metabolic transformation occurs in the liver through conjugation with glucuronic acid and omega-, omega-1 and beta-oxidation. More than 20 metabolites have been found that have a hepatotoxic effect as a result of omega-oxidation.

Valproic acid is excreted in breast milk at a concentration of 1-10% of the total serum level. The drug is excreted mostly by the kidneys after glucuronidation and beta-oxidation, less than 5% is excreted unchanged. In patients with epilepsy, the plasma clearance of the drug is 12.7 ml / min, the half-life (T _1/2) is 15-17 hours.

The agent does not have the ability to induce enzymes belonging to the cytochrome P450 family.

Indications for use

According to the instructions, Depakine Chrono is recommended as a monotherapy drug or in combination with other antiepileptic drugs for the treatment of the following diseases in children and adults:

• generalized epileptic seizures: tonic, clonic, tonic-clonic, atonic, myoclonic, absences;
• Lennox-Gastaut syndrome;
• partial epileptic seizures (with or without secondary generalization).

In adult patients, Depakine Chrono is also used for the prevention and treatment of bipolar disorder.

Contraindications

Absolute:

• severe functional disorders of the liver or pancreas;
• acute / chronic hepatitis;
• severe liver disease (especially drug-induced hepatitis), indicated in the patient's individual or family history;
• severe liver pathologies with a fatal outcome when using valproic acid in close blood relatives;
• hepatic porphyria;
• established violations of the urea cycle (urea cycle), due to the threat of the development of hyperammonemia;
• combined use with mefloquine, St. John's wort preparations;
• age up to 6 years;
• diagnosed mitochondrial diseases caused by mutations in the nuclear gene encoding the mitochondrial enzyme γ-polymerase (POLG), including Alpers-Huttenlocher syndrome and suspected pathology caused by defects (POLG);
• hypersensitivity to any component of the drug, as well as to valpromide or valproate seminatrium.

Relative (it is recommended to take Depakine Chrono with extreme caution):

• congenital fermentopathies;
• history of liver and pancreas damage;
• renal failure;
• hypoproteinemia;
• oppression of bone marrow hematopoiesis (thrombocytopenia, leukopenia, anemia);
• pregnancy;
• the simultaneous use of several anticonvulsants (the risk of liver damage increases);
• combination with neuroleptics, monoamine oxidase (MAO) inhibitors, antidepressants, benzodiazepines;
• the simultaneous use of drugs that provoke seizures or lower the threshold for seizure readiness, including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, phenothiazine / butyrophenone derivatives, tramadol, bupropion, chloroquine (the threat of seizures);
• combination with the following drugs: lamotrigine, primidone, phenobarbital, phenytoin, felbamate, zidovudine, aztreonam, propofol, olanzapine, acetylsalicylic acid, carbapenems, indirect anticoagulants, erythromycin, cimetidine, nimodipinamidine, rifinamatramine, carbamazepine;
• insufficiency of carnitine palmitoyltransferase (CBT) type II (against the background of taking valproic acid, the threat of rhabdomyolysis is aggravated).

Instructions for the use of Depakine Chrono: method and dosage

Depakine Chrono is intended only for adults and children over 6 years of age with a body weight exceeding 17 kg.

The drug is taken orally. The tablets are swallowed without chewing or crushing, but they can be divided to facilitate taking the individually selected dose. It is recommended to take the daily dose in one or two doses, preferably with meals.

When using Depakine Chrono, due to the slow release of the active substance, after administration there are no sharp peak rises in the level of its content in the blood, and a uniform concentration of the drug in the plasma remains for a longer period of time throughout the day.

The daily dose of the drug is set by the attending physician individually. In order to prevent epileptic seizures, Depakine Chrono must be taken in the minimum effective dose.

The optimal dose for the treatment of epilepsy should be established mainly based on the clinical response, since no clear relationship has been found between the plasma concentration of the agent, the daily dose and the therapeutic effect. Plasma valproic acid can be measured in addition to clinical observation when side effects are suspected or seizure control cannot be achieved.

The range of the therapeutic concentration of the drug in the blood, as a rule, is 40–100 mg / l. The daily dose is determined based on age and body weight. When conducting monotherapy, Depakine Chrono is usually prescribed at an initial dose of 5-10 mg / kg, which is then gradually increased every 4-7 days at the rate of 5 mg valproic acid per 1 kg of body weight until the most favorable dose is reached, allowing control over epileptic seizures.

Recommended average daily doses of valproic acid for long-term use (depending on age and body weight):

• children 6-14 years old (body weight 20-30 kg) - 30 mg / kg (600-1200 mg);
• adolescents (body weight 40-60 kg) - 25 mg / kg (1000-1500 mg);
• adults and elderly patients (body weight from 60 kg and more) - an average of 20 mg / kg (1200–2100 mg).

When setting the daily dose, individual sensitivity to valproate should also be taken into account.

If epilepsy is uncontrollable, an increase in these doses is allowed while monitoring the patient's condition and the level of the drug in the blood. The full therapeutic effect of Depakine Chrono can sometimes be achieved not immediately, but only 4–6 weeks after the start of administration. Therefore, you should not increase the daily dose above the recommended one earlier than this period. In the case of adequately controlled epilepsy, the dose can be taken once a day.

If you need to change the dosage form of the drug Depakine not prolonged action on Depakine chrono, this can usually be done immediately or for several days, continuing to take it in the previously selected daily dose.

Patients who have previously received other antiepileptic drugs should gradually switch to Depakine Chrono, reaching the optimal dose of valproic acid for about 14 days. In this case, the dose of the previously taken drug should be immediately reduced, especially if it is phenobarbital, and the cancellation should be carried out gradually.

Since other antiepileptic drugs have the ability to reversibly induce liver microsomal enzymes, the level of valproic acid in the blood should be monitored for 4-6 weeks after taking their last dose, and, if necessary, the daily dose should be reduced.

If combined therapy with other anticonvulsants is prescribed, they must be started gradually.

For the treatment of manic episodes in bipolar disorder in adults, it is recommended to take the drug at an initial dose of 750 mg. Also, according to the results of clinical studies, you can use the agent in an initial daily dose of 20 mg sodium valproate per 1 kg of body weight. The initial dose should be increased as quickly as possible to the lowest effective dose to achieve the desired clinical effect. The average daily dose can range from 1000 to 2000 mg sodium valproate. If patients receive Depakine Chrono at a dose exceeding 45 mg / kg of body weight per day, they need careful medical supervision.

While continuing the treatment of manic episodes in bipolar disorders, Depakine Chrono should be taken in the minimum individually selected effective dose.

Side effects

• blood coagulation system: often - hemorrhage and bleeding; rarely - a decrease in the level of blood coagulation factors; an increase in prothrombin time (PTT), activated partial thromboplastin time (APTT), thrombin time, international normalized ratio (MHO) (the occurrence of spontaneous bleeding and ecchymosis requires discontinuation of the drug);
• hematopoietic system: often - thrombocytopenia, anemia; infrequently - leukopenia, pancytopenia (with or without depression of bone marrow hematopoiesis), neutropenia (reversible after discontinuation);
• nervous system: very often - tremor; often - drowsiness, headache, dizziness, memory impairment, nystagmus, convulsions *, stupor *, extrapyramidal disorders; infrequently - paresthesia, ataxia, reversible parkinsonism, increased severity of seizures, lethargy *, encephalopathy *, coma *; rarely - cognitive disorders, reversible dementia with reversible brain atrophy; with an unknown frequency - sedation;
• mental disorders: infrequently - impaired attention **, aggressiveness **, agitation **, confusion, depression (when combined with other anticonvulsants); rarely - learning disabilities **, psychomotor hyperactivity **, behavioral disorders **, depression (with monotherapy);
• sense organs: often - reversible / irreversible deafness; with an unknown frequency - diplopia;
• liver and biliary tract: often - liver damage, accompanied by a decrease in the prothrombin index (PTI) (especially in combination with a pronounced decrease in the level of blood coagulation factors and fibrinogen), an increase in the concentration of bilirubin and an increase in the activity of hepatic transaminases in the blood; liver failure, in exceptional cases - with a fatal outcome;
• digestive system: very often - nausea; often - hyperplasia and other changes in the gums, vomiting, epigastric pain, stomatitis, diarrhea (usually occur at the beginning of the course, and disappear on its own after a few days; the frequency of effects can be reduced by taking the remedy during or after meals); infrequently - pancreatitis, sometimes fatal; with an unknown frequency - increased appetite, anorexia, abdominal cramps;
• urinary system: infrequently - renal failure; rarely - tubulointerstitial nephritis, enuresis, reversible Fanconi syndrome (expressed as a complex of clinical and biochemical manifestations of renal tubular damage with altered tubular reabsorption of glucose, phosphate, bicarbonate and amino acids);
• respiratory system: infrequently - pleural effusion;
• vascular disorders: infrequently - vasculitis;
• musculoskeletal system and connective tissue: infrequently - osteopenia, decreased bone mineral density, fractures and osteoporosis (with long-term treatment); rarely - rhabdomyolysis, systemic lupus erythematosus;
• endocrine system: infrequently - syndrome of inadequate secretion of antidiuretic hormone (ADH), hyperandrogenism (acne, virilization, hirsutism, male pattern alopecia and / or increased androgen levels in the blood); rarely - hypothyroidism;
• reproductive system and mammary glands: often - dysmenorrhea; infrequently - amenorrhea; rarely - polycystic ovary disease, male infertility; with an unknown frequency - an increase in the mammary glands, irregular menstruation, galactorrhea;
• immune system: often - hypersensitivity reactions (including urticaria); infrequently - angioedema; rarely, drug rash syndrome with eosinophilia and systemic symptoms;
• skin and subcutaneous tissues: often - transient / dose-dependent alopecia (including androgenic alopecia on the background of arising: polycystic ovary disease, hyperandrogenism, hypothyroidism), disorders of the nail bed and nails; infrequently - a rash, discoloration and / or a violation of the normal structure of the hair, abnormal hair growth (the disappearance of curly and wavy hair or the appearance of curly with initially straight hair); rarely - Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme;
• benign, undefined and malignant tumors (including cysts and polyps): rarely - myelodysplastic syndrome;
• laboratory and instrumental studies: rarely - biotinidase deficiency or biotin deficiency;
• metabolism: often - hyponatremia, weight gain (dietary correction is necessary to prevent it; weight gain must be controlled, since this is a factor contributing to the appearance of polycystic ovary syndrome); rarely - obesity, hyperammonemia with the possible appearance of neurological symptoms (including ataxia, vomiting, encephalopathy - in this case, the cancellation of therapy is required);
• general disorders: mild peripheral edema, hypothermia.

* lethargy and stupor sometimes caused transient coma / encephalopathy and were isolated or proceeded with an increase in convulsive seizures during the treatment period, and also decreased in case of cancellation or reduction of the Depakine chrono dose; the predominant part of such reactions was described against the background of a combined admission.

** violations observed mainly in children.

Overdose

Symptoms of acute overdose are coma with miosis, hyporeflexia, muscle hypotonia, marked decrease in blood pressure, respiratory depression, metabolic acidosis, and vascular collapse / shock. Due to the presence of chrono sodium in Depakine, hypernatremia may appear.

Cases of intracranial hypertension due to cerebral edema and seizures at very high plasma concentrations of valproic acid have been described. A significant overdose can be fatal, however, in most cases, the prognosis is favorable.

In this condition, emergency care is required in the hospital: gastric lavage (no later than 10-12 hours after an overdose), taking activated charcoal, maintaining effective diuresis, monitoring the function of the cardiovascular and respiratory systems, pancreas, and liver. In extremely severe cases, artificial lung ventilation, hemoperfusion and hemodialysis are prescribed.

special instructions

Before using the drug or before surgery, as well as when observing spontaneous subcutaneous bleeding or hematomas, the number of peripheral blood cells (including the number of platelets) and bleeding time should be determined.

Before treatment with Depakine Chrono and periodically during the first 6 months of the course, liver function parameters should be assessed, especially in patients at risk. It should be borne in mind that against the background of therapy, mainly at the beginning of admission, an isolated and transient increase in the level of transaminases may occur, which does not manifest clinically. With this violation, it is recommended to conduct a detailed study of biological indicators, including the determination of PTI, and, if necessary, revise the dosage, and then perform a repeated laboratory examination.

There have been very rare reports of severe (fatal) cases of liver damage when using Depakine Chrono. According to clinical experience, the high-risk group includes patients receiving several antiepileptic drugs at the same time, children under three years of age with severe epilepsy, as well as patients using salicylates at the same time. In children over 3 years of age, the threat of liver damage is significantly reduced, and the frequency of its occurrence decreases with age. This complication is usually noted during the first 6 months of therapy, mainly between 2 and 12 weeks, against the background of combined antiepileptic treatment.

Patient monitoring is necessary to detect early signs of liver damage. It is required to pay attention to the development of symptoms that may indicate the subsequent onset of jaundice, such as anorexia, asthenia, drowsiness, lethargy, sometimes accompanied by abdominal pain and repeated vomiting (especially suddenly appearing), as well as the recurrence of seizures in patients with epilepsy. If you observe any of these symptoms, you should consult a doctor and conduct a clinical examination and analysis of liver function.

To detect violations of liver activity before the start of the course and during its first 6 months, it is recommended to periodically monitor liver function, including the mandatory determination of PTI. When there is a significant decrease in the level of prothrombin, fibrinogen and blood coagulation factors, an increase in the activity of hepatic transaminases and the concentration of bilirubin, it is required to stop using Depakine Chrono. You should also refuse concomitant therapy with salicylates, if it was previously performed.

Cases of severe forms of pancreatitis have been observed in children and adults. Risk factors for this complication can be anticonvulsant treatment, neurological disorders, and severe seizures. The threat was highest in young children, but it decreased with age. Liver failure in pancreatitis increased the risk of death. Patients who develop vomiting, anorexia, nausea, acute abdominal pain during therapy require immediate medical examination. When diagnosing pancreatitis, including an increase in the activity of pancreatic enzymes, Depakine Chrono should be discontinued.

There is information about the occurrence in patients taking antiepileptic drugs, suicidal thoughts / attempts, but the mechanism of this effect is not clear. As a result, patients receiving Depakine Chrono should be carefully monitored for the timely detection of possible suicidal thoughts or inclinations, and if they develop, immediately seek medical attention.

Due to the threat of polycystic ovary disease, amenorrhea, dysmenorrhea, an increase in testosterone levels, a decrease in fertility may be observed in women during therapy. In men, sperm motility and fertility can be impaired. These violations go away on their own after completion of treatment.

In patients with diabetes mellitus, it is necessary to carefully monitor the level of glucose in the blood due to the possible negative effect of the drug on the pancreas. When examining ketone bodies in urine, false positive results can be obtained.

While taking valproic acid, some patients may develop a reversible paradoxical increase in the severity and frequency of seizures or new types of seizures. In case of aggravation of seizures, an urgent need to consult a doctor.

In children with mental retardation, or with a history of unexplained gastrointestinal symptoms (vomiting, anorexia, cases of cytolysis), lethargy or coma, as well as with family history of the death of a newborn or child, it is necessary to conduct studies before starting treatment with the drug metabolism, in particular ammonia (fasting and after meals).

Patients on a low sodium diet should remember that the Depakine Chrono 300 mg tablet contains 27.6 mg of sodium, and the Depakine Chrono 500 mg tablet contains 46.1 mg.

It is not recommended to consume alcoholic beverages while taking the drug.

Influence on the ability to drive vehicles and complex mechanisms

Patients driving vehicles and other complex equipment during the period of treatment, especially when combining Depakine Chrono with benzodiazepines, should take into account the risk of drowsiness.

Application during pregnancy and lactation

Depakine Chrono should not be used in women of reproductive age, pregnant women and female children (adolescents), unless other methods of therapy are not tolerated by the patient or do not achieve the desired effect. With regular revision of treatment, the balance of benefit and risk should be carefully evaluated.

Women with childbearing potential during the period of taking the drug need to use effective contraceptive drugs. When planning a pregnancy (before conception), it is necessary to take, if possible, all measures to transfer the patient to an appropriate alternative treatment.

The occurrence of generalized tonic-clonic epileptic seizures, status epilepticus with the development of hypoxia during pregnancy, due to the possible lethal outcome, may pose a particular threat to the woman and the fetus.

In the course of experimental studies of reproductive toxicity in animals, valproic acid was found to have a teratogenic effect.

According to the available clinical data, in children whose mothers took valproic acid as a monotherapy drug during pregnancy, the risk of congenital malformations exceeded approximately 3.7 / 2.3 / 2.3 / 1.5 times, a similar threat when compared with lamotrigine / phenobarbital / carbamazepine / phenytoin monotherapy, respectively. The risk associated with valproic acid was 10.73% and was higher than the risk of severe congenital malformations in the general population, which was 2–3%. This threat is dose-dependent, but it is impossible to determine the threshold dose below which there is no threat. The most frequently noted defects were congenital craniofacial deformities, neural tube defects, hypospadias, malformations of the cardiovascular system and extremities, and defects of other systems and organs.

It has been established that as a result of intrauterine exposure to valproic acid, violations of the physical and mental development of children can occur. During the study of children at risk of preschool age, 30–40% were found to have delayed early development, memory impairment, a lower level of intellectual abilities, and poor speech skills. Also, in children aged 6 years, the IQ was on average 7–10 points lower than in children who were exposed to intrauterine effects of other antiepileptic drugs.

There are limited data on long-term outcomes, indicating that in children whose mothers took Depakine Chrono during pregnancy, there was an increase in the risk of developing autism spectrum disorders (including childhood autism) and attention deficit / hyperactivity disorder (ADHD).

Risk factors for fetal malformations include the intake by pregnant women of daily doses over 1000 mg (while the use of lower doses does not exclude this threat) and the combination of valproic acid with other anticonvulsants.

Based on the foregoing, the use of Depakine Chrono during pregnancy and in women of reproductive age is allowed only when absolutely necessary.

In the event that a woman is planning a pregnancy, or the pregnancy has already begun, the need for valproic acid therapy should be urgently reviewed, taking into account the indications. When treating a drug for bipolar disorder, consideration should be given to discontinuing its use. If a patient receives valproic acid for epilepsy, the question of whether to continue or to stop taking the drug is decided after reassessing the ratio of the expected benefit and possible risk. If it is necessary to continue treatment during pregnancy, Depakin Chrono, it is prescribed in the lowest effective dose, which should be divided into several doses per day. Against the background of pregnancy, receiving a sustained release agent is more preferable than taking other dosage forms.

In addition to therapy even before pregnancy is diagnosed, folic acid can be added at a dose of 5 mg per day to reduce the risk of neural tube malformations (at present, its preventive effect has not been confirmed). Permanent (including the third trimester of pregnancy) special antenatal monitoring should be carried out for the possible detection of malformations, including neural tube defects. Before giving birth, a woman needs to have coagulation tests, including platelet count, fibrinogen level, and APTT.

Valproic acid in small amounts (1–10% of the serum concentration) is excreted in breast milk. But due to limited clinical data on the use of the substance during breastfeeding, taking Depakine Chrono during lactation is not recommended.

Pediatric use

In newborns whose mothers received valproic acid during pregnancy, isolated cases of hemorrhagic syndrome associated with hypofibrinogenemia, thrombocytopenia, and / or a decrease in the level of other blood coagulation factors were recorded. Fatal afibrinogenemia has also been reported. Therefore, in newborns from this risk group, it is imperative to conduct coagulation tests.

There is evidence of the development of hypothyroidism, and when mothers use Depakine chrono in the third trimester of pregnancy, hypoglycemia and withdrawal syndrome (difficulties with feeding, irritability, tremors, hyperreflexia, hyperkinesia, muscle tone disorders, seizures) in newborns.

Depakine chrono is contraindicated in children under 6 years of age because of the possible ingestion of the tablet when swallowing into the respiratory tract. For children over 6 years old, the drug is prescribed in an average daily dose of 30 mg / kg.

Evaluation of the safety and efficacy of using the drug for the treatment of manic episodes associated with bipolar disorders in patients under 18 years of age has not been carried out.

With impaired renal function

In the presence of renal failure, it may be necessary to reduce the dosage of Depakine Chrono.

For violations of liver function

Taking Depakine chrono is contraindicated in functional disorders of the liver.

Use in the elderly

In elderly patients, the dose should be adjusted to ensure effective control of epileptic seizures.

Drug interactions

The effect of valproic acid on simultaneously used substances / drugs:

• antidepressants, MAO inhibitors, antipsychotics, benzodiazepines and other psychotropic drugs: their effect is enhanced (if necessary, a dose change is required);
• primidone: its concentration in plasma increases, which causes an increase in side reactions (including sedation), with prolonged combined use, these symptoms disappear, but dose adjustment may be required;
• lithium preparations: serum lithium concentration does not change;
• carbamazepine: clinical manifestations of toxicity may develop, due to an increase in the content of the active metabolite of Depakine chrono in plasma, with signs of overdose (dose adjustment may be required);
• phenobarbital: the level of the drug in the blood rises, a sedative effect is possible, especially in children; careful monitoring is required during the first 15 days of therapy with an immediate dose reduction with the development of sedation;
• phenytoin: the total plasma concentration decreases, the concentration of the free fraction increases, the development of overdose symptoms is possible;
• lamotrigine: metabolism in the liver slows down, and T _1/2 rises almost 2 times; possible aggravation of toxicity (severe skin reactions, including toxic epidermal necrolysis); dose reduction may be required;
• zidovudine: increases in plasma levels, increases toxicity (mainly hematological effects); monitoring of laboratory parameters and condition is necessary, especially during the first two months of combined treatment;
• olanzapine: plasma concentration decreases;
• felbamate: the average values of its clearance are reduced (by 16%);
• rufinamide: the level in plasma increases (the effect is especially pronounced in children);
• propofol: plasma concentrations increase;
• nimodipine: the hypotensive effect is enhanced as a result of an increase in its level in plasma;
• temozolomide: there is a mild, but statistically significant, decrease in clearance.

Effect of concurrently taken substances / drugs on valproic acid:

• ritonavir, lopinavir, cholestyramine, rifampicin, antiepileptic drugs leading to the induction of microsomal liver enzymes (phenobarbital, phenytoin, carbamazepine, primidone, etc.): reduce the plasma concentration of valproic acid, dose adjustment is required taking into account the clinical response;
• phenytoin, phenobarbital: the level of metabolites in serum increases, the condition should be monitored to identify possible signs of hyperammonemia;
• aztreonam: the risk of seizures is aggravated due to a decrease in the concentration of the antiepileptic drug; the dose should be adjusted during and after taking aztreonam;
• St. John's wort preparations: inhibit the anticonvulsant efficacy of the drug;
• mefloquine: the metabolism of valproic acid increases and there is a risk of developing an epileptic seizure;
• felbamate, cimetidine, erythromycin: the plasma level rises, it may be necessary to change the dose of Depakine Chrono during and after combined use;
• panipenem, meropenem, imipenem (carbapenems): concentrations of valproic acid decrease rapidly and intensively (in 2 days the decrease can be 60–100%), which can cause the development of seizures; during combined administration and after its completion, the level of Depakine chrono should be monitored;
• acetylsalicylic acid: the concentration of the free fraction of valproic acid increases;
• warfarin and other coumarin derivatives: IPT and INR should be monitored.

Other types of interactions of valproic acid:

• topiramate or acetazolamide: the combination is associated with the development of encephalopathy and / or hyperammonemia; careful monitoring is necessary for the development of symptoms of these complications;
• quetiapine: the risk of neutropenia / leukopenia is aggravated;
• estrogen-progestogen drugs: the effectiveness of these drugs is not reduced;
• ethanol, other potentially hepatotoxic drugs: the hepatotoxic effect of valproic acid may be aggravated;
• medicines that have a myelotoxic effect: the danger of inhibition of bone marrow hematopoiesis increases;
• clonazepam: there is a possibility of increased severity of absence status.

Analogs

Depakine chrono analogs are Valproic acid, Valopixime, Valparin, Valparin XP, Depakine, Depakine Chronosphere, Depakine enteric 300, Konvuleks, Konvulsofin, Konvulsofin-retard, Enkorat, Enkorat chrono.

Terms and conditions of storage

Store in a place protected from moisture at temperatures below 25 ° C. Keep out of the reach of children!

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Depakine Chrono

Most of the reviews about Depakine Chrono are positive. Patients taking the drug note its effectiveness in the treatment of epileptic seizures. However, there are also negative reviews about the effectiveness of treatment.

Almost all patients attribute to the disadvantages of the remedy a very large number of side effects of varying intensity. Dissatisfaction with the high cost of the drug is also often expressed.

Price for Depakine Chrono in pharmacies

The price of Depakine Chrono, depending on the dosage, can be approximately:

• Depakine Chrono 300 mg: 100 pcs. in the package - 1000-1200 rubles;
• Depakine Chrono 500 mg: 30 pcs. in the package - 550-650 rubles.

Depakine chrono: prices in online pharmacies

Drug name Price Pharmacy

Depakine chrono 500 mg film-coated tablets of prolonged action 30 pcs. 214 r Buy

Depakine Chrono tablets p.p. prolonged action 500mg 30 pcs. 223 r Buy

Depakine chrono 300 mg film-coated tablets of prolonged action 100 pcs. 598 r Buy

Depakine Chrono tablets p.p. prolonged action 300mg 100 pcs. RUB 615 Buy

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!