Valproic Acid - Instructions For Use, Price, Drug Analogues, Reviews

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

Valproic acid

Valproic acid: 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: Valproic acid

ATX code: N03AG01

Active ingredient: valproic acid (Valproic acid)

Manufacturer: JSC "R-Pharm" (Russia); Obninsk Chemical-Pharmaceutical Company CJSC (Russia); Izvarino Pharma LLC (Russia)

Description and photo update: 2019-11-07

Prices in pharmacies: from 229 rubles.

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Valproic acid is an antiepileptic drug with a central muscle relaxant, pronounced normotimic and sedative effect.

Release form and composition

The drug is produced in the form of extended-release tablets (with prolonged release), film-coated: white or almost white, oval, biconvex, the core of the tablet is white or almost white (30 or 100 pcs. In vials, in a cardboard box 1 bottle; 20, 30, 40, 50 or 100 pcs.in cans, in a cardboard bundle 1 can; 10 pcs.in blister strip packs, in a cardboard bundle 1, 2, 3, 4, 5, 6 or 10 packs. each pack also contains instructions for the use of Valproic acid).

1 tablet contains:

• active substance: sodium valproate - 300 mg (including sodium valproate - 199.8 mg; valproic acid - 87 mg) or 500 mg (including sodium valproate - 333 mg; valproic acid –145 mg);
• auxiliary components: sodium saccharinate, silicon dioxide, hypromellose 4000, colloidal silicon dioxide, ethyl cellulose;
• shell composition: white Opadray II film coating - polyvinyl alcohol, macrogol 4000, titanium dioxide, talc.

Pharmacological properties

Pharmacodynamics

Valproic acid is an antiepileptic drug that has a central muscle relaxant and sedative effect, improves mental state and mood, and has antiarrhythmic activity.

The active substance of the drug is valproic acid, which is a derivative of a group of fatty acids. The most likely mechanism of action of sodium valproate and valproic acid is considered to be the effect on the synthesis and subsequent metabolism of gamma-aminobutyric acid (GABA), which leads to an increase in its inhibitory effect, as well as a direct cardiotropic effect.

Pharmacokinetics

When taken orally, the bioavailability of sodium valproate and valproic acid is about 100%.

Against the background of the use of the drug in a daily dose of 1000 mg, the minimum concentration (C _min) in plasma can range from 0.0349 to 0.0545 mg / ml. The maximum concentration (C _max) in plasma is achieved in a time from 4.35 to 8.81 hours and averages 0.0816 mg / ml. Equilibrium concentration occurs after 3-4 days of regular therapy.

The permissible concentration of valproic acid in plasma should not exceed 100 mg / l, otherwise the likelihood of side effects, including the development of intoxication, increases. At a plasma concentration of the drug above 150 mg / l, a dose reduction is required.

The volume of distribution is usually 0.13–0.19 l per 1 kg of body weight (l / kg), it depends on age, so in elderly patients it can reach 0.23 l / kg.

The substance binds well to blood plasma proteins - 90–95% (mainly albumin), the degree of binding is dose-dependent and saturable. In old age and with renal or hepatic insufficiency, the connection with blood plasma proteins decreases. In severe renal failure, the level of the free fraction of valproic acid in the blood plasma may increase to 8.5–20%.

In patients with hypoproteinemia, the total level of valproic acid (free fraction and associated with blood plasma proteins) may decrease due to an increase in the metabolism of the free fraction.

In cerebrospinal fluid, the level of valproic acid corresponds to 10% of the total concentration. The substance is excreted in breast milk, the equilibrium concentration can reach 10% of its serum level.

Three pathways of valproic acid metabolism in the liver have been established: about 50% of the total dose of the drug - glucuronidation; about 40% - beta, omega, and omega-1 oxidation; about 10% - oxidation mediated by cytochrome P ₄₅₀. In total, more than 20 of its metabolites have been identified. Those that are formed as a result of mitochondrial oxidation are hepatotoxic. Valproic acid does not induce microsomal liver enzymes, therefore, unlike most other antiepileptic drugs, it does not affect the degree of its own metabolism and other substances (including estrogens, progestogens, indirect anticoagulants).

After conjugation with glucuronic acid and beta-oxidation, the substance is excreted mainly through the kidneys, including less than 5% unchanged.

In patients with epilepsy, the plasma clearance of valproic acid is 12.7 ml / min.

T _1/2 (half-life) in adults and children over the age of two months is usually 15-17 hours, but in some cases it can range from 8 to 20 hours.

In renal insufficiency, the dose of the drug should be adjusted taking into account the level of its concentration in plasma. Usually, the amount of the free fraction is 6-15% of the total plasma valproic acid level, however, there is no clear dependence of the pharmacological activity of the drug on the amount of the free fraction or the total plasma concentration of the substance.

The simultaneous use of Valproic acid with antiepileptic drugs that induce liver microsomal enzymes increases the plasma clearance of the drug and decreases T _1/2, the degree of these changes depends on the level of induction of microsomal liver enzymes by other antiepileptic drugs.

With liver diseases, T _1/2 increases, in case of an overdose, it can be 30 hours. During hemodialysis, only the free fraction of valproic acid in the blood is excreted, which is 10%.

Pharmacokinetics of a substance during pregnancy has its own characteristics. An increase in the volume of distribution in the third trimester leads to an increase in its renal clearance. At the same time, even while taking the drug in a constant dose, a decrease in its serum concentrations is possible. Among other things, during pregnancy, it is possible to change the relationship of valproic acid with blood plasma proteins, causing an increase in the content of its free (therapeutically active) fraction in blood serum.

Valproic acid is a prolonged release dosage form of the active ingredient. Comparison of equivalent doses of the drug and enteric-coated tablets demonstrates the advantages of prolonged-release tablets in terms of the absence of delayed absorption and prolongation of the absorption period against the background of identical bioavailability. This dosage form also provides a decrease in C _{max by} about 25%, but a more stable plateau phase in the period from 4 to 14 hours after administration, a more linear correlation between the dose taken and the level of the drug in plasma. Prolonged release of the active substance allows you to avoid sharp rises in its concentration in the blood and to keep the blood level unchanged for a longer period of time.

Indications for use

The use of Valproic acid is indicated for pediatric and adult patients in monotherapy or in combination with other antiepileptic drugs in the treatment of the following diseases:

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

In addition, in adults, the drug is used for the prevention and treatment of bipolar affective disorders.

In pediatrics, the drug is also used to treat childhood tics and febrile seizures in children.

Contraindications

Absolute:

• acute or chronic hepatitis;
• hepatic porphyria;
• a history of medicinal hepatitis or other severe liver disease (including close blood relatives);
• severe liver damage with a fatal outcome in close blood relatives of the patient, arising from the use of valproic acid;
• severe liver and / or pancreatic dysfunction;
• established mitochondrial pathologies due to mutations in the nuclear gene that encodes the mitochondrial enzyme gamma polymerase, including Alpers (- Huttenlocher's) syndrome, and suspicion of diseases caused by gamma polymerase defects;
• established violations of the urea cycle (urea cycle);
• concomitant therapy with mefloquine, St. John's wort preparations;
• breast-feeding;
• age under 6 years old or body weight less than 17 kg;
• hypersensitivity to valproic acid, sodium valproate, seminatrium valproate, valpromide or ancillary components of the drug.

It is recommended to prescribe Valproic acid tablets with caution to patients with a history of liver and pancreas diseases, renal failure, congenital fermentopathies, inhibition of bone marrow hematopoiesis (leukopenia, anemia, thrombocytopenia), in case of deficiency of carnitine palmitoyltransferase in the period of type II, a pregnancy.

In addition, caution is required with the simultaneous use of the drug with the following drugs: other anticonvulsants, other drugs that reduce the seizure threshold or cause seizures (tricyclic antidepressants, selective serotonin reuptake inhibitors, phenothiazine derivatives, chloroquine, bupropion, tramadol, derivatives butyrophenone), carbamazepine, topiramate, acetazolamide, monoamine oxidase (MAO) inhibitors, neuroleptics, antidepressants, benzodiazepines; phenobarbital, primidone, phenytoin, lamotrigine, zidovudine, felbamate, acetylsalicylic acid, indirect anticoagulants, cimetidine, erythromycin, carbapenems, nimodipine, rufinamide (especially in children), rifampicin, protease inhibitors, lopiraminavirinavironavir.

Valproic acid, instructions for use: method and dosage

I take Valproic acid tablets orally, without chewing or crushing, simultaneously with food or after eating (this helps to reduce the incidence of undesirable reactions from the digestive system).

The dosage form of the drug, due to the prolonged release of the active substance, allows, after taking the tablets, to avoid a sharp increase in the concentration of valproic acid and for a longer time (within a day) ensures the stability of its level in the blood.

In order to facilitate the administration of the individual dose, the 300 or 500 mg tablets can be divided.

Due to the risk of getting the tablet into the respiratory tract during swallowing, valproic acid in this dosage form is not recommended for children under 6 years of age.

Epilepsy therapy

The doctor sets the daily dose individually in accordance with the age, body weight of the patient and personal sensitivity to valproate; it can be divided into several doses during the day.

It is recommended to take the minimum effective dose to prevent the development of seizures (especially during pregnancy), which is selected by gradually increasing the initial dose of the drug.

The optimal dose of a drug for the treatment of epilepsy is determined by clinical response. In cases where epilepsy cannot be controlled or there is a suspicion of the development of adverse events, in addition to clinical observation, the determination of the concentration of valproic acid in the blood plasma can be used. Its therapeutic concentration usually ranges from 40 mg / L to 100 mg / L (300-700 µmol / L).

Usually, the initial daily dose of valproic acid in monotherapy is 5-10 mg per 1 kg of body weight. It is gradually increased at the rate of 5 mg per 1 kg of body weight every 4-7 days until the dose is sufficient to control epileptic seizures.

The recommended daily dosage for long-term use of the drug, taking into account the age and body weight of the patient:

• children 6-14 years old (body weight 20-30 kg): based on 30 mg of valproic acid per 1 kg of body weight (on average, from 600 mg to 1200 mg);
• adolescents (body weight 40-60 kg): 25 mg per 1 kg of body weight (on average, 1000 mg to 1500 mg);
• adults, including elderly patients (body weight 60 kg and more): 20 mg / kg, on average, 1200–2100 mg.

The dose can be divided into 2 doses; with well-controlled epilepsy, a single daily dose is possible.

It should be borne in mind that the therapeutic effect of the drug develops gradually, it fully manifests itself after 28–42 days of therapy. If epilepsy cannot be adequately controlled, the dose should be increased, taking into account the concentration of valproic acid in the blood and the patient's response to therapy.

When switching to Valproic acid, the size of the daily dose of sodium valproate should be maintained, which provided sufficient control over the disease when taking immediate-release tablets of the active substance.

After treatment with other antiepileptic drugs, the transition to valproic acid should be made within 14 days, gradually reaching the optimal dose of the drug. At the same time, it is necessary to reduce the dose of the previous antiepileptic drug, especially phenobarbital.

Due to the fact that the means of previous therapy can reversibly induce liver microsomal enzymes, during the first 28–42 days after switching to valproic acid, careful monitoring of its plasma level is required. If necessary, the daily dose of the drug can be reduced, taking into account the degree of decrease in the inducing effect of previously taken drugs on the metabolism of valproic acid.

In cases where additional prescription of other antiepileptic drugs is required, they should be introduced into the treatment regimen gradually.

Therapy for Manic Episodes in Bipolar Disorders

The attending physician selects the daily dose of the drug individually.

The recommended starting daily dose for the treatment of bipolar disorder in adult patients with manic episodes is 750 mg or 20 mg sodium valproate per 1 kg of body weight.

The dose escalation period until the minimum clinically effective dose is reached should be as short as possible. The desired therapeutic effect can be achieved by taking sodium valproate in a dose of 1000 mg to 2000 mg per day. If the daily dose is more than 45 mg / kg, then the patient should be under close medical supervision.

In the further treatment of manic episodes in bipolar disorders, an individually adjusted minimum effective dose should be used.

Therapy for special groups of patients

Initiation of treatment for female children and adolescents, women of childbearing potential or pregnant women should be under the supervision of a specialist with experience in the treatment of epilepsy and bipolar disorders. The appointment of valproic acid in this category of patients should be made only in case of ineffectiveness or intolerance to other methods of treatment, subject to regular careful re-evaluation of the benefit-risk ratio. Monotherapy with valproic acid is preferred, using the lowest effective doses of sustained-release dosage forms. During pregnancy, the daily dose must be divided into 2 or more doses.

Changes in the pharmacokinetics of valproic acid revealed in elderly patients are of limited clinical significance.

When choosing a dose in patients with renal failure and / or hypoproteinemia, one should focus mainly on the clinical picture.

Side effects

• mental disorders: often - aggressiveness, agitation and / or impaired attention (more often in children), hallucinations, confusion, against the background of a combination with other anticonvulsants - depression; rarely - depression with monotherapy, more often in children - behavioral disorders, psychomotor hyperactivity and / or learning disabilities;
• congenital, hereditary and genetic disorders: teratogenic risk;
• on the part of the blood and lymphatic system: often - anemia, thrombocytopenia; infrequently - leukopenia and pancytopenia (including those with bone marrow depression) are transient - the blood picture returns to normal after drug withdrawal, neutropenia; rarely - disorders of bone marrow hematopoiesis (including agranulocytosis, isolated plasma or hypoplasia of erythrocytes, macrocytosis, macrocytic anemia), a decrease in the content of factors (at least one) of blood coagulation, an increase in such indicators of blood coagulation as prothrombin time, APTT (activated partial thromboplastin time) thrombin time or international normalized ratio (INR), symptoms of their deviation from the norm may be spontaneous ecchymosis and bleeding;
• from the nervous system: very often - tremor; often - stupor and convulsions (more often in children), drowsiness, extrapyramidal disorders, memory impairment, nystagmus, headache, dizziness; infrequently - ataxia, paresthesia, reversible parkinsonism, coma (more often in children), encephalopathy (more often in children), lethargy (more often in children); rarely - cognitive disorders, reversible dementia, combined with reversible brain atrophy; frequency not established - sedation;
• from the digestive system: very often - nausea; often - epigastric pain, vomiting, diarrhea, stomatitis, changes in the gums (more often gingival hyperplasia); infrequently - pancreatitis, including fatal; frequency not established - increased appetite, abdominal cramps, anorexia;
• on the part of the hepatobiliary system: often - liver damage (violations of the indicators of the functional state of the liver - a decrease in the prothrombin index, including in combination with a significant decrease in the content of fibrinogen and blood coagulation factors, an increase in the concentration of bilirubin and the activity of hepatic transaminases in the blood), hepatic failure, in including fatalities;
• on the part of metabolism and nutrition: often - weight gain, hyponatremia; rarely - hyperammonemia (including cases of hyperammomoniemia, accompanied by the development of vomiting, encephalopathy, ataxia and other neurological symptoms, requiring discontinuation of therapy), obesity;
• on the part of the organ of hearing, labyrinth disorders: often - reversible or irreversible deafness;
• on the part of the organ of vision: the frequency is not established - diplopia;
• from the respiratory system, chest and mediastinum: infrequently - pleural effusion;
• from the urinary system: infrequently - renal failure; rarely - enuresis, tubulointerstitial nephritis, reversible Fanconi syndrome (damage to the proximal renal tubules, causing impaired tubular reabsorption of glucose, phosphate, amino acids, bicarbonate);
• from the genitals and mammary gland: often - dysmenorrhea; infrequently - amenorrhea; rarely - polycystic ovary disease, male infertility; frequency not established - enlargement of the mammary glands, irregular menstruation, galactorrhea;
• from the musculoskeletal system: infrequently - a decrease in bone mineral density, osteopenia, against the background of long-term therapy - bone fractures, osteoporosis; rarely - systemic lupus erythematosus, rhabdomyolysis;
• on the part of the endocrine system: infrequently - syndrome of inadequate secretion of antidiuretic hormone, hyperandrogenism (acne, hirsutism, virilization, male-type alopecia, an increase in the level of androgens in the blood); rarely - hypothyroidism;
• from the skin and subcutaneous tissues: often - hypersensitivity reactions (including itching, urticaria), disorders of the nails (including the nail bed), alopecia (pathological hair loss is reversible and / or dose-dependent), androgenetic alopecia (against the background of hyperandrogenism, polycystic ovaries), alopecia due to hypothyroidism; infrequently - rash, hirsutism, acne, angioedema, hair disorders (including changes in the structure or color of the hair, disappearance of waviness and curly hair, or the appearance of curly in patients with initially straight hair); rarely - drug-related eosinophilia with systemic symptoms, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme;
• benign and malignant neoplasms, including cysts and polyps: rarely - myelodysplastic syndrome;
• from the side of the vessels: often - hemorrhage, bleeding; infrequently - vasculitis;
• general disorders: infrequently - mild peripheral edema, hypothermia;
• laboratory and instrumental parameters: rarely - biotinidase deficiency, biotin deficiency.

Overdose

• symptoms of an overdose of valproic acid: respiratory depression, miosis, hyporeflexia, metabolic acidosis, excessive lowering of blood pressure, coma with muscle hypotension, vascular collapse or shock, including death. Perhaps the development of hypernatremia, intracranial hypertension (which is associated with cerebral edema), seizures;
• treatment: if no more than 12 hours have passed after an overdose, it is necessary to wash the stomach, take activated charcoal (including its introduction using a nasogastric tube). Maintenance of effective diuresis, control of liver and pancreas function is required; ensuring careful monitoring of the state of the cardiovascular and respiratory systems, if necessary, artificial ventilation of the lungs should be carried out. Naloxone can be used as an antidote. The use of hemodialysis and hemoperfusion sessions is effective.

special instructions

When valproic acid is prescribed and regularly during the first six months of therapy, liver function should be monitored, especially if the patient has a predisposition to the development of its lesion. Studies of liver function tests should reflect the state of the protein-synthetic function of the liver, the determination of the prothrombin index.

Before starting treatment, it is necessary to conduct a study to determine the number of corpuscles in the peripheral blood, including platelets, and bleeding time. A similar examination is required in the case of spontaneous occurrence of bleeding and subcutaneous hematomas in a patient, or before surgery.

It should be borne in mind that the risk of developing severe forms of pancreatitis exists in both children and adults, and it does not depend on the duration of treatment. In children, the likelihood of pancreatitis is especially high, but as the child grows up, it decreases. Risk factors include neurologic disorders, severe seizures, or anticonvulsant therapy. When liver failure is combined with pancreatitis, the risk of death increases. In case of severe abdominal pain, nausea, vomiting and / or anorexia, an immediate examination is required. If the diagnosis of pancreatitis is confirmed, then the intake of valproic acid should be stopped immediately.

Close and caring for the patient should be informed about the need for constant monitoring for the appearance of suicidal thoughts and attempts, and the obligatory visit to a doctor if they are found.

Before starting treatment, the patient needs to conduct a metabolic study in case of suspected enzyme deficiency of the carbamide cycle.

The adverse effects of valproic acid on the pancreas should be considered in patients with diabetes mellitus and the blood glucose level should be carefully monitored. In this category of patients, it is possible to obtain false positive results when examining urine for the presence of ketone bodies.

Patients with type II CBT deficiency are at increased risk of developing rhabdomyolysis while taking the drug.

During therapy, it is recommended to avoid the use of alcoholic beverages and ethanol-containing drugs.

Influence on the ability to drive vehicles and complex mechanisms

During the period of use of the drug, especially when combining valproic acid with other antiepileptic drugs or benzodiazepines, it is recommended to be careful when driving vehicles and performing other activities that require increased concentration of attention and speed of psychomotor reactions.

Application during pregnancy and lactation

The use of valproic acid in women with childbearing potential and during pregnancy is indicated only in cases of extreme necessity, when treatment with other antiepileptic drugs is ineffective or when they are intolerant.

It is preferable to use valproic acid in the form of monotherapy in a daily dose of up to 1000 mg, in dosage forms with prolonged release.

Valproic acid has a teratogenic effect, causing minor and severe malformations of various systems / organs of the fetus, including congenital defects of the neural tube, craniofacial deformity, malformations of the cardiovascular system and limbs. Children exposed to it in utero may have a delay in early development (delayed mastery of walking skills, speech development), lower intellectual abilities, memory problems, and difficulty understanding speech.

Compared with antiepileptic drugs such as phenytoin, carbamazepine, phenobarbital and lamotrigine, children born to mothers with epilepsy who received monotherapy with valproic acid during pregnancy have a higher risk of congenital malformations. Therefore, when deciding whether to use the drug, one should carefully weigh the existing potential risks and the expected benefits of therapy.

During treatment with the drug, women of childbearing age are required to avoid conception, they should be advised to use reliable methods of contraception.

When planning pregnancy or already diagnosed conception, the doctor needs to determine the possibility of continuing treatment with the drug, depending on the clinical condition of the patient. A woman should be informed about such risks to newborns from the use of valproic acid during gestation as the development of hemorrhagic syndrome (associated with thrombocytopenia, hypofibrinogenemia and / or a decrease in the content of other blood coagulation factors), afibrinogenemia, hypoglycemia, hypothyroidism. Taking the drug in the third trimester of pregnancy can cause withdrawal syndrome in newborns, manifested by agitation, impaired muscle tone, irritability, tremor, hyperreflexia, tremors, hyperkinesia, convulsions, and difficulties in feeding.

It is not recommended to take the drug during breastfeeding.

On the background of treatment with Valproic acid, a reversible impairment of fertility in men and women is possible.

Pediatric use

The use of Valproic acid is contraindicated for the treatment of children under the age of 6 years or with a body weight of up to 17 kg.

There is no assessment of the effectiveness and safety of using the drug in patients under 18 years of age in the treatment of manic episodes in bipolar disorders.

With impaired renal function

Valproic acid should be used with caution in renal failure.

For violations of liver function

It is contraindicated to use valproic acid for the treatment of patients with acute or chronic hepatitis, hepatic porphyria, severe liver dysfunction, a history of drug-induced hepatitis or other severe liver damage (including close blood relatives, including fatalities after using valproic acid) …

The drug should be prescribed with caution in case of liver disease in history.

Use in the elderly

For elderly patients, the dose of the drug should be selected individually and ensure control over epileptic seizures.

Drug interactions

• antidepressants, neuroleptics, benzodiazepines, monoamine oxidase (MAO) inhibitors: potentiation of the action of these and other psychotropic drugs is possible, therefore, when they are included in concomitant therapy, the patient should be provided with careful medical supervision, and, if necessary, adjust the doses of psychotropic drugs;
• lithium preparations: serum lithium concentrations are not disturbed;
• phenobarbital: the hepatic metabolism of phenobarbital decreases, causing an increase in its plasma concentration and the development of a sedative effect, especially in children. Therefore, during the first 15 days of combination therapy, it is recommended to carefully monitor the patient's condition; if a sedative effect occurs, it is necessary to reduce the dose of phenobarbital;
• primidone: valproic acid increases the plasma concentration of primidone and enhances its side effects;
• phenytoin: There is a decrease in total plasma concentrations of phenytoin. Valproic acid, displacing phenytoin from the connection with plasma proteins, slows down its hepatic catabolism, which leads to an increase in the level of the free phenytoin fraction and the risk of overdose symptoms;
• carbamazepine, zidovudine: the toxic effects of these drugs are potentiated;
• lamotrigine: the metabolism of lamotrigine in the liver slows down, increasing 2 times T _1/2. Interaction with valproic acid can lead to an increase in the toxicity of lamotrigine, including the development of toxic epidermal necrolysis and other severe skin reactions;
• felbamate: it is possible to lower the average clearance of felbamate by 16%, and the clearance of valproic acid by 22-50%, causing an increase in its plasma concentration;
• olanzapine: valproic acid helps to reduce its plasma concentrations;
• rufinamide: an increase in its plasma concentration is possible, the degree of which depends on the level of valproic acid in the blood;
• nimodipine: valproic acid inhibits the metabolism of nimodipine, which leads to an increase in its plasma concentration and an increase in the hypotensive effect;
• temozolomide: there is a mild, but clinically significant decrease in its clearance;
• phenobarbital, phenytoin, carbamazepine and other antiepileptic drugs that induce microsomal liver enzymes: help to reduce the plasma concentration of valproic acid. The combination with phenytoin or phenobarbital can increase the concentration of its metabolites in the blood serum, increase the risk of hyperammonemia;
• mefloquine: potentiates the metabolism of valproic acid, can cause seizures;
• St. John's wort preparations: help to reduce the anticonvulsant effect of valproic acid;
• acetylsalicylic acid: concomitant therapy with acetylsalicylic acid or other agents with a high and strong binding to plasma proteins can lead to a clinically significant increase in the level of the free fraction of valproic acid;
• indirect anticoagulants (including coumarin derivatives): careful monitoring of the prothrombin index is required when combined with indirect anticoagulants;
• cimetidine, erythromycin: these agents help slow down the hepatic metabolism of valproic acid and increase its serum concentration;
• carbapenems (meropenem, imipenem, panipenem), rifampicin: cause a therapeutically significant decrease in the concentration of valproic acid in the blood;
• lopinavir, ritonavir, cholestyramine: reduce the plasma concentration of valproic acid;
• topiramate, acetazolamide: the interaction of these drugs with valproic acid is associated with hyperammonemia and / or encephalopathy, therefore, when combined, careful medical supervision is required for the development of symptoms of hyperammonemic encephalopathy;
• quetiapine: increases the risk of developing neutropenia or leukopenia;
• hormonal contraceptives: estrogen-progestogen drugs do not reduce their effectiveness;
• ethanol: combination with potentially hepatotoxic agents, including ethanol, may enhance the hepatotoxic effect of valproic acid;
• clonazepam: the risk of increased severity of absence status increases;
• myelotoxic drugs: contribute to the inhibition of bone marrow hematopoiesis.

Analogs

Valproic acid analogs are Valopixime, Valparin, Valparin XP, Depakine, Depakine Chrono, Depakine Chronosphere, Depakine Enteric 300, Konvuleks, Konvulsofin, Konvulsofin-retard, Enkorat, Encorat chrono, etc.

Terms and conditions of storage

Keep out of the reach of children.

Store at temperatures up to 25 ° C in a dark place.

Shelf life of tablets, depending on the packaging: vials - 2 years; contour cell packs and cans - 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Valproic acid

This drug is included in the list of vital and essential drugs (vital and essential drugs), however, there are practically no reviews of Valproic acid in this dosage form from patients.

Pediatricians, based on many years of experience in the clinical use of valproic acid, the results of scientific research and observations, argue that despite the competition of more modern drugs, valproic acid in their practice is the number one drug for the treatment of a wide range of different types of seizures and epileptic syndromes in children. …

Price for Valproic acid in pharmacies

Price for Valproic acid for a package containing tablets in a dose of 300 mg, per 100 pcs. can be from 741 rubles, 30 pcs. - from 275 rubles; tablets in a dose of 500 mg: 100 pcs. - from 1527 rubles, 30 pcs. - from 436 rubles.

Valproic acid: prices in online pharmacies

Drug name Price Pharmacy

Valproic acid 300 mg film-coated tablets with prolonged release 30 pcs. 229 r Buy

Valproic acid tablets p.o. with prolonged release. 300mg 30 pcs. 293 r Buy

Valproic acid 500 mg film-coated tablets with prolonged release 30 pcs. 323 r Buy

Valproic acid tablets p.o. with prolonged release. 300mg 100 pcs. 861 RUB Buy

Valproic acid 300 mg film-coated tablets with prolonged release 100 pcs. 861 RUB 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!