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What is valproic acid for? Valproic acid preparations in the treatment of epilepsy and convulsive conditions

Valproic acid (as sodium salt)
- valproic acid
- sodium valproate (valproic acid)

Composition and release form of the drug

Extended-release film-coated tablets from white to almost white with a yellowish tint, oval, biconvex, with a mark on one side and an “f” embossed on the other.

Excipients: hypromellose, sodium saccharinate, colloidal silicon dioxide, ethylcellulose, sodium stearyl fumarate.

Film shell composition: opadry II white 85F18422 (polyvinyl alcohol, titanium dioxide, macrogol 3350, talc).

10 pcs. - contour cellular packaging (PVC/PVDC/aluminum foil) (3) - cardboard packs.
10 pcs. - contour cellular packaging (PVC/PVDC/aluminum foil) (5) - cardboard packs.
10 pcs. - contour cellular packaging (PVC/PVDC/aluminum foil) (10) - cardboard packs.
30 pcs. - polyethylene cans (1) - cardboard packs.
50 pcs. - polyethylene cans (1) - cardboard packs.
100 pcs. - polyethylene cans (1) - cardboard packs.

Pharmacological action

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

Pharmacokinetics

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

C ss is achieved on days 2-4 of treatment, depending on the intervals between doses. Plasma protein binding is 80-95%. Concentration levels in cerebrospinal fluid correlate with the size of the fraction not bound to proteins. Valproic acid penetrates the placental barrier and is excreted in breast milk.

Metabolized by glucuronidation and oxidation in the liver.

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

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

Indications

Epileptic seizures: generalized, focal (focal, partial) with simple and complex symptoms, minor. Convulsive syndrome in organic brain diseases. Behavioral disorders associated with epilepsy. Manic-depressive psychosis with a bipolar course that cannot be treated with lithium or other medications. Febrile convulsions in children, childhood tics.

Contraindications

Severe liver dysfunction; severe pancreatic dysfunction; porphyria; hemorrhagic diathesis; severe thrombocytopenia; I trimester of pregnancy; lactation ( breast-feeding); increased sensitivity to valproic acid.

Dosage

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

Frequency of administration: 2-3 times/day with meals.

IV (in the form of sodium valproate) is administered at a dose of 400-800 mg or dropwise at a rate of 25 mg/kg for 24, 36 and 48 hours. If simultaneous use orally and intravenously is necessary, the first administration is carried out by intravenous infusion at a dose of 0.5-1 mg/kg/hour 4-6 hours after the last oral dose.

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

Side effects

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

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

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

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

From the gynecological status: menstrual irregularities.

Dermatological reactions: alopecia.

Allergic reactions: skin rash.

Drug interactions

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

With the simultaneous use of drugs that have a hepatotoxic effect, the hepatotoxic effect may be enhanced.

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

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

When used simultaneously with, the concentration of valproic acid in the blood plasma decreases due to an increase in the rate of its metabolism caused by the induction of microsomal liver enzymes under the influence of carbamazepine. Valproic acid potentiates the toxic effect of carbamazepine.

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

When used simultaneously with mefloquine, the metabolism of valproic acid in the blood plasma increases and the risk of developing seizures increases.

When used simultaneously with meropenem, a decrease in the concentration of valproic acid in the blood plasma is possible; with primidone - increased concentration of primidone in blood plasma; with salicylates - it is possible to enhance the effects of valproic acid due to its displacement by salicylates from its connection with blood plasma proteins.

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

When used simultaneously with phenytoin during the first few weeks, the total concentration of phenytoin in the blood plasma may decrease due to its displacement from plasma protein binding sites by sodium valproate, induction of microsomal liver enzymes and acceleration of phenytoin metabolism. Next, the metabolism of phenytoin is inhibited by valproate and, as a result, the concentration of phenytoin in the blood plasma increases. Phenytoin reduces plasma concentrations of valproate, probably by increasing its metabolism in the liver. It is believed that phenytoin, as an inducer of liver enzymes, may also increase the formation of a minor, but hepatotoxic, metabolite of valproic acid.

With simultaneous use, valproic acid displaces its binding to plasma proteins, resulting in an increase in its concentration in the blood plasma. Phenobarbital increases the rate of metabolism of valproic acid, which leads to a decrease in its concentration in the blood plasma.

There are reports of increased effects of fluvoxamine when used simultaneously with valproic acid. When used concomitantly with fluoxetine, some patients experienced an increase or decrease in the concentration of valproic acid in the blood plasma.

With the simultaneous use of cimetidine and erythromycin, it is possible to increase the concentration of valproic acid in plasma due to a decrease in its metabolism in the liver.

Special instructions

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

In patients receiving other anticonvulsants, treatment with valproic acid should be initiated gradually, reaching a clinically effective dose after 2 weeks. Then the gradual withdrawal of other anticonvulsants is carried out. In patients not treated with other anticonvulsants, a clinically effective dose should be achieved after 1 week.

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

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

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

Impact on the ability to drive vehicles and operate machinery

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

Pregnancy and lactation

Valproic acid is excreted in breast milk. Concentrations of valproate in breast milk have been reported to be 1-10% of maternal plasma concentrations. Use during breastfeeding is contraindicated.

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

Use in childhood

For impaired renal function

Use with caution in case of impaired renal function.

For liver dysfunction

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

It should be borne in mind that the risk of side effects from the liver is increased during combination anticonvulsant therapy. During treatment, liver function should be regularly monitored.

Anticonvulsant, effective in various forms epilepsy. It is believed that valproate increases the concentration of GABA in the central nervous system by inhibiting the enzyme GABA transferase.
Well absorbed in the digestive tract. The maximum serum concentration is observed 1-4 hours after oral administration. When selecting a dose, it must be borne in mind that the level of the active substance in the CSF is about 1/10 of its concentration in the blood. Excreted primarily in urine as a glucuronide; half-life - 8-15 hours, in patients taking antiepileptic drugs for a long time - 6-10 hours. After oral administration active substance penetrates the placental barrier and also enters breast milk.

Indications for use of the drug Valproic acid

Generalized and minor epileptic seizures; focal (partial) seizures with simple and complex symptoms; convulsive syndrome in organic brain diseases; behavioral disorders associated with epilepsy; febrile seizures in children; tic in children.

Use of the drug Valproic acid

Adults and adolescents - daily dose 20-30 mg/kg body weight; to achieve a sustainable clinical effect, the dose can be increased by 200 mg/day with an interval of 3-4 days; the highest daily dose is 50 mg/kg. Take orally with meals 2-3 times a day. Newborns and children early age the dose is selected individually: the daily dose is usually 30 mg/kg; the frequency of administration in children under 1 year of age is 2 times, in older children - 3 times a day.

Contraindications to the use of the drug Valproic acid

Hypersensitivity to valproate; dysfunction of the liver and pancreas, hemorrhagic diathesis.

Side effects of the drug Valproic acid

Possible nausea, vomiting, diarrhea, dysfunction of the liver and pancreas, isolated stuporous state, ataxia, tremor, skin rash, angioedema, anemia, thrombocytopenia, prolongation of bleeding time, leukopenia, rarely - alopecia, increased appetite, weight gain, amenorrhea and menstrual irregularities.

Special instructions for the use of the drug Valproic acid

Children under 3 years of age are at greatest risk of developing liver dysfunction when using valproate. During the first 6 months of treatment, it is necessary to regularly monitor liver function tests, blood composition and prothrombin levels.
Use during pregnancy can cause birth defects in 1-2% of cases neural tube in the fetus (meningocele, vertebral bifida). For women of reproductive age, treatment should not be interrupted; monotherapy is recommended in the minimum effective dose, distributed over several doses per day.

Drug interactions Valproic acid

Valproic acid potentiates the effect of neuroleptics and antidepressants; increases the concentration of barbiturates in the blood plasma; reduces the total concentration of phenytoin, increasing the concentration of its free fraction. Anticonvulsants- inducers of microsomal liver enzymes (phenytoin, phenobarbital, carbamazepine) - reduce the concentration of valproic acid in the blood serum.

Overdose of the drug Valproic acid, symptoms and treatment

Clinical manifestations of acute massive overdose usually occur in the form of coma of varying degrees with muscle hypotonia, hyporeflexia, miosis and respiratory depression. Urgent Care in a hospital should include gastric lavage (effectively within 10-12 hours after taking the tablets), osmotic diuresis, constant monitoring of cardiovascular and respiratory systems. In severe cases, dialysis or exchange transfusion is indicated. There is only one report of the successful use of naloxone in acute poisoning valproic acid. In case of very high overdose, death is possible, but in general the prognosis for overdose is favorable.

List of pharmacies where you can buy Valproic acid:

Saint Petersburg

Gross formula

C8H16O2

Pharmacological group of the substance Valproic acid

Nosological classification (ICD-10)

CAS code

99-66-1

Characteristics of the substance Valproic acid

White fine crystalline powder. Easily soluble in water and alcohol.

Pharmacology

Pharmacological action- antiepileptic, muscle relaxant, sedative.

By inhibiting GABA transferase, it increases the content of gamma-aminobutyric acid in the central nervous system, which causes a decrease in the threshold of excitability and the level of convulsive readiness of the motor areas of the brain. When taken orally, it dissociates to valproate ion, which is absorbed into the blood plasma. Food reduces the rate of absorption. C max in plasma is determined after 1-4 hours. The therapeutic concentration in the blood is 50-100 mcg/ml (can be significantly higher or lower, depending on the permeability of the BBB in a given patient). Binding to blood plasma proteins is about 90%. Metabolized in the liver: most of it is glucuronidated, a smaller part is oxidized with the participation of either microsomal enzymes or in the mitochondria of hepatocytes (beta-oxidation). T1/2 ranges from 6 to 16 hours and depends mainly on the activity of microsomal liver enzymes. Metabolites and conjugates are excreted by the kidneys. A small amount of valproic acid is excreted in milk.

Application of the substance Valproic acid

Various forms of generalized seizures: small (absences), large (convulsive) and polymorphic; used for focal seizures, childhood tics.

Contraindications

Hypersensitivity, incl. “familial” (death of close relatives while taking valproic acid), diseases of the liver and pancreas (in some patients, a significant decrease in metabolism in the liver is possible), hemorrhagic diathesis.

Restrictions on use

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

Use during pregnancy and breastfeeding

Breastfeeding should be stopped during treatment.

Side effects of the substance Valproic acid

Nausea, vomiting, diarrhea, stomach pain, anorexia or increased appetite, liver dysfunction, drowsiness, tremor, paresthesia, confusion, peripheral edema, bleeding, leukopenia, thrombocytopenia. Long-term use may result in temporary hair loss.

Interaction

The effect is enhanced by other anticonvulsants, sedatives and hypnotics. Dyspeptic disorders develop less frequently against the background of antispasmodics and enveloping agents. Alcohol and other hepatotoxic drugs increase the likelihood of liver damage, anticoagulants or acetylsalicylic acid- risk of bleeding.

Routes of administration

Inside.

Interactions with other active ingredients

Trade names

Name	The value of the Vyshkowski Index ®
	0.0633
	0.0548
	0.0336
	0.025
	0.0056

Valproic acid INN (long-acting granules for oral administration)

INN
Valproic acid
Dosage form
long-acting granules for oral administration
Chemical name
2 - propylvaleric acid (as calcium, magnesium or sodium salt) Description

White fine-crystalline powder, easily soluble in water and ethanol.
Pharmacological action

An antiepileptic drug that has a central muscle relaxant and sedative effect. The mechanism of action is associated with an increase in the content of GABA in the central nervous system (due to inhibition of GABA transferase, as well as a decrease in the reuptake of GABA in the brain), resulting in a decrease in the excitability and convulsive readiness of the motor areas of the brain. According to another hypothesis, it acts on sites of postsynaptic receptors, simulating or enhancing the inhibitory effect of GABA. A possible direct effect on membrane activity is associated with changes in K+ conductance. Improves the mental state and mood of patients, has antiarrhythmic activity.
Pharmacokinetics

Absorption - high, food slightly reduces the rate of absorption; bioavailability - 100%. TCmax of capsules and syrup - 1-4 hours, tablets - 3-4 hours, controlled-release tablets - 2-8 hours, with intravenous administration - by the end of 1 hour of infusion. Css is achieved on days 2-4 of administration (depending on the intervals between doses). Therapeutic plasma concentrations range from 50-150 mg/l. The pharmacological and therapeutic effects of controlled-release formulations are not always dependent on plasma concentrations. Volume of distribution - 0.2 l/kg. Communication with plasma proteins is 90-95% (at plasma concentrations up to 50 mg/l), at concentrations of 50-100 mg/l it decreases to 80-85%; with uremia, hypoproteinemia and liver cirrhosis, binding to plasma proteins is also reduced.

Penetrates the placental barrier and the BBB; excreted in breast milk (the concentration in breast milk is 1-10% of the concentration in maternal plasma). The content in the CSF correlates with the size of the fraction not bound to proteins. Metabolized by glucuronidation and oxidation in the liver, T1/2 - 8-22 hours.

Valproic acid (1-3%) and its metabolites (in the form of conjugates, oxidation products, including ketometabolites) are excreted by the kidneys; small amounts are excreted in feces and exhaled air.

When combined with other medicinal drugs, T1/2 can be 6-8 hours due to the induction of metabolic enzymes; in patients with impaired liver function, elderly patients and children under 18 months, it can be significantly longer.

The prolonged form is characterized by the absence of absorption latency, slow absorption, lower (25%), but relatively more stable plasma concentrations between 4 and 14 hours.
Indications for use

Epilepsy of various origins.

Epileptic seizures (including generalized and partial seizures, as well as against the background of organic brain diseases).

Changes in character and behavior (due to epilepsy).

Febrile convulsions (in children), childhood tics.

Manic-depressive psychosis with a bipolar course, not amenable to treatment with Li+ drugs or other drugs.

Specific syndromes (Vest, Lennox-Gastaut).
Contraindications

Hypersensitivity, liver failure, acute and chronic hepatitis, pancreatic dysfunction, porphyria, hemorrhagic diathesis, severe thrombocytopenia, lactation.
With caution

Suppression of bone marrow hematopoiesis (leukopenia, thrombocytopenia, anemia), history of organic brain diseases, liver and pancreas diseases; hypoproteinemia, mental retardation in children, congenital enzymopathies, renal failure, pregnancy, children under 3 years of age.
Dosage regimen

Orally, during meals or immediately after meals, without chewing, with a small amount of water, 2-3 times a day. The syrup can be mixed with any liquid or added to small amounts of food.

The initial dose for monotherapy for adults and children weighing more than 25 kg is 5-15 mg/kg/day, then this dose is gradually increased by 5-10 mg/kg/week. The maximum dose is 30 mg/kg/day (can be increased if it is possible to monitor the plasma concentration to 60 mg/kg/day).

With combination therapy in adults - 10-30 mg/kg/day, followed by increasing the dose by 5-10 mg/kg/week.

For children weighing less than 25 kg, the average daily dose for monotherapy is 15-45 mg/kg, the maximum is 50 mg/kg. Depending on age: newborns - 30 mg/kg, from 3 to 10 years - 30-40 mg/kg/day, up to 1 year - in 2 doses, in older people - in 3 doses. With combination therapy - 30-100 mg/kg/day.

Children weighing less than 20 kg should not use controlled-release tablets.

IV stream, 400-800 mg or IV drip, at a rate of 25 mg/kg for 24, 36, 48 hours. If you decide to switch to IV administration after oral administration, the first administration is carried out at a dose of 0.5-1 mg/kg/hour 4-6 hours after the last oral dose.
Side effect

From the side of the central nervous system: tremor; rarely - changes in behavior, mood or mental state (depression, feeling tired, hallucinations, aggressiveness, hyperactive state, psychosis, unusual agitation, restlessness or irritability), ataxia, dizziness, drowsiness, headache, encephalopathy, dysarthria, enuresis, stupor, disturbance of consciousness, coma.

From the sensory organs: diplopia, nystagmus, flickering of “spots” before the eyes.

From the digestive system: nausea, vomiting, gastralgia, decreased or increased appetite, diarrhea, hepatitis; rarely - constipation, pancreatitis, up to severe injuries with a fatal outcome (in the first 6 months of treatment, more often at 2-12 weeks).

From the hematopoietic organs and hemostasis system: inhibition of bone marrow hematopoiesis (anemia, leukopenia); thrombocytopenia, decreased fibrinogen content and platelet aggregation, leading to the development of hypocoagulation (accompanied by prolongation of bleeding time, petechial hemorrhages, bruises, hematomas, bleeding, etc.).

Metabolism: loss or increase in body weight.

Allergic reactions: skin rash, urticaria, angioedema, photosensitivity, malignant exudative erythema(Stevens-Johnson syndrome).

Laboratory indicators: hypercreatininemia, hyperammonemia, hyperglycinemia, hyperbilirubinemia, slight increase in the activity of liver transaminases, LDH (dose-dependent).

From the outside endocrine system: dysmenorrhea, secondary amenorrhea, breast enlargement, galactorrhea.

Other: peripheral edema, alopecia.
Overdose

Symptoms: nausea, vomiting, dizziness, diarrhea, respiratory dysfunction, muscle hypotonia, hyporeflexia, miosis, coma.

Treatment: gastric lavage (no later than 10-12 hours), taking activated carbon, forced diuresis, maintenance of vital functions, hemodialysis.
Interaction

Valproic acid enhances the effects, incl. side effects, other antiepileptic drugs (phenytoin, lamotrigine), antidepressants, antipsychotic drugs (neuroleptics), anxiolytics, barbiturates, MAO inhibitors, thymoleptics, ethanol. The addition of valproic acid to clonazepam in isolated cases can lead to increased severity of absence status.

With simultaneous use of valproic acid with barbiturates or primidone, an increase in the concentration of the latter in plasma is observed.

Increases T1/2 of lamotrigine (suppresses liver enzymes, causes a slowdown in the metabolism of lamotrigine, as a result of which T1/2 is extended to 70 hours in adults and to 45-55 hours in children).

Reduces the clearance of zidovudine by 38%, while its T1/2 does not change.

Tricyclic antidepressants, MAO inhibitors, antipsychotic drugs (neuroleptics), and other drugs that lower the seizure threshold reduce the effectiveness of valproic acid.

When combined with salicylates, an increase in the effects of valproic acid is observed (displacement from connection with plasma proteins), enhances the effect of antiplatelet agents (ASA) and indirect anticoagulants.

When combined with phenobarbital, phenytoin, carbamazepine, mefloquine, the content of valproic acid in the blood serum decreases (acceleration of metabolism).

Felbamate increases the concentration of valproic acid in plasma by 35-50% (dose adjustment is necessary).

With the simultaneous use of valproic acid with ethanol and other drugs that depress the central nervous system (tricyclic antidepressants, MAO inhibitors and antipsychotic drugs), increased depression of the central nervous system is possible.

Ethanol and other hepatotoxic drugs increase the likelihood of developing liver damage.

Valproic acid does not induce liver microsomal enzymes and does not reduce the effectiveness of oral contraceptives.

Myelotoxic drugs - increased risk of inhibition of bone marrow hematopoiesis.
Special instructions

During treatment, it is advisable to monitor the activity of liver transaminases, bilirubin concentration, peripheral blood patterns, blood platelets, the state of the blood coagulation system, amylase activity (every 3 months, especially when combined with other antiepileptic drugs).

For patients receiving other antiepileptic drugs, transfer to valproic acid should be carried out gradually, reaching a clinically effective dose after 2 weeks, after which gradual withdrawal of other antiepileptic drugs is possible. In patients who have not received treatment with other antiepileptic drugs, a clinically effective dose should be achieved after 1 week.

The risk of side effects from the liver is increased during combination anticonvulsant therapy, as well as in children.

Drinks containing ethanol are not allowed.

Before surgery it is necessary general analysis blood (including platelet count), determination of bleeding time, coagulogram parameters.

If symptoms of an “acute” abdomen occur during treatment before surgical intervention It is recommended to determine amylase activity in the blood to exclude acute pancreatitis.

During treatment, possible distortion of urine test results should be taken into account when diabetes mellitus(due to an increase in the content of ketone bodies), indicators of thyroid function.

If any acute serious side effects develop, you should immediately discuss with your doctor the advisability of continuing or stopping treatment.

To reduce the risk of developing dyspeptic disorders, it is possible to take antispasmodics and enveloping drugs.

Abruptly stopping valproic acid may lead to an increase in epileptic seizures.

During treatment, care must be taken when managing vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Formula: C8H16O2, chemical name: 2-Propylvaleric acid (and in the form of calcium, magnesium or sodium salt).
Pharmacological group: neurotropic drugs/antiepileptic drugs; neurotropic drugs / mood stabilizers.
Pharmacological action: muscle relaxant, antiepileptic, sedative.

Pharmacological properties

Valproic acid, due to inhibition of the enzyme GABA transferase, increases the concentration in the central nervous system gamma-aminobutyric acid, which leads to a decrease in the level of convulsive readiness and the threshold of excitability of the motor areas of the brain. After oral administration, valproic acid dissociates to valproate ion, which is absorbed into the blood plasma. Food reduces the rate of absorption. The maximum concentration of valproic acid in the blood plasma is achieved within 1 to 4 hours. The therapeutic level of valproic acid in the blood is 50 - 100 mcg/ml (depending on the permeability of the blood-brain barrier in each individual patient, it can be significantly lower or higher). Valproic acid is approximately 90% bound to plasma proteins. Valproic acid is metabolized in the liver: the main part is glucuronidated, the remaining is oxidized either in the mitochondria of hepatocytes (beta-oxidation) or with the participation of microsomal enzymes. The half-life of valproic acid ranges from 6 to 16 hours (depending on the activity of microsomal liver enzymes). Conjugates and metabolites of valproic acid are excreted by the kidneys. Valproic acid is excreted in breast milk.

Indications

Various forms of generalized seizures: large (convulsive), small (absences), polymorphic; childhood tics, focal seizures.

Method of administration of valproic acid and dose

Valproic acid is taken orally, immediately after or during meals. For adults, the daily dose at the beginning of therapy is 0.3 - 0.6 g, over 7 - 14 days it is gradually increased to 0.9 - 1.5 g, a single dose for adults is 0.3 - 0.45 g. For children, the daily dose is 15 - 50 mg/kg (at the beginning of therapy - 15 mg/kg, then gradually increase by 5 - 10 mg/kg per week).

When treating with valproic acid, it is advisable to monitor the level of bilirubin, the activity of liver transaminases, the activity of amylase, blood platelets, peripheral blood patterns, and the state of the blood coagulation system (every 3 months, especially when used together with other antiepileptic drugs). For patients receiving other antiepileptic drugs, transfer to the use of valproic acid should be carried out gradually, after 2 weeks reaching a clinically effective dose, only then is it possible to gradually withdraw other antiepileptic drugs. In patients who have not received therapy with other antiepileptic drugs, a clinically effective dose should be achieved after 1 week. Development risk adverse reactions from the liver is higher when using combined anticonvulsant treatment, as well as in patients under 18 years of age. During therapy, it is necessary to refrain from engaging in potentially hazardous activities (including driving), which require rapid psychomotor reactions and increased concentration. Drinks that contain ethanol are not allowed. Before surgery, it is necessary to conduct a general blood test, determine coagulogram parameters, and bleeding time. If symptoms of an acute abdomen develop during therapy with valproic acid, it is necessary to determine the level of amylase in the blood before surgery to exclude acute pancreatitis. If any acute serious adverse reactions occur, you must immediately inform your doctor and decide whether to stop or continue therapy. To reduce the likelihood of developing dyspepsia, it is possible to take enveloping agents and antispasmodics. Abrupt withdrawal of valproic acid may lead to an increase in epileptic seizures.

Contraindications for use

Hypersensitivity, including familial (death of close relatives when using valproic acid), hemorrhagic diathesis, diseases of the pancreas and liver (in some patients there may be a marked decrease in the metabolism of valproic acid in the liver).

Restrictions on use

Bone marrow aplasia, childhood.

Use during pregnancy and breastfeeding

The use of valproic acid is contraindicated in the 1st trimester of pregnancy. In the 2nd and 3rd trimester of pregnancy, use is possible if the expected effects of treatment for the mother are higher than the possible risk to the fetus. While taking valproic acid, you must stop breastfeeding.

Side effects of valproic acid

Nausea, diarrhea, vomiting, stomach pain, increased appetite or anorexia, liver dysfunction, confusion, tremor, drowsiness, paresthesia, peripheral edema, leukopenia, bleeding, thrombocytopenia; with prolonged use - temporary hair loss.

Interaction of valproic acid with other substances

The effects of valproic acid are enhanced by other anticonvulsants, hypnotics and sedatives. When taking enveloping agents and antispasmodics, dyspeptic disorders caused by taking valproic acid are less likely to develop. Hepatotoxic drugs (including alcohol) increase the risk of liver damage, acetylsalicylic acid or anticoagulants increase the possibility of bleeding.