Valparin

Has restrictions during pregnancy

Prohibited during breastfeeding

Has restrictions for children

Has restrictions for older people

Has limitations for liver problems

Has limitations for kidney problems

Today, among anticonvulsants, drugs that contain valproic acid are especially popular. One such medicine is Valparin. This drug can effectively relieve the symptoms of convulsive attacks of any severity. According to the instructions for use, Valparin is prescribed for various types of epilepsy in both adults and children.

Release form and composition

The dosage form of the drug is long-acting tablets, film-coated: the shell is white, the outer layer and the white core stand out at the break; at a dose of 300 mg – round, biconvex; at a dose of 500 mg - oblong, with a notch on both sides (4 pcs. in Al foil strips, 1 strip in a cardboard pack; 10 pcs. in Al foil strips, 1, 3, 5 or 10 strips in a cardboard pack ).

1 tablet contains:

active ingredient: sodium valproate – 300 or 500 mg (sodium valproate – 200 or 333 mg + valproic acid – 87 or 145 mg);
excipients: hypromellose, silicon dioxide hydrate, colloidal silicon dioxide, ethylcellulose, sodium saccharinate;
film shell I: titanium dioxide, hypromellose, glycerol;
film shell II: hypromellose, macrogol-1500, Eudragit E-100, Eudragit NE-30D, macrogol-1500, titanium dioxide, talc.

Similar means

Popular analogues of Volparin are drugs based on valproic acid. Among them:

Depakine. An effective anticonvulsant, which is available in various dosage forms (syrup, tablets, powder for the preparation of solution for injection). There is even a type of drug that is gentle on the stomach (Depakine Enteric). Produced pharmaceutically. The cost of Depakine (500 mg) is 680 rubles.
Convulex. A German medicine that, in addition to its antiepileptic effect, is also effective in preventing migraines. Available in the form of syrup, drops, injections and tablets. The price of the drug is from 340 (300 mg) to 510 (500 mg) rubles.
Encorat Chrono. An Indian anticonvulsant drug based on valproate, produced only in tablet form. It has a more affordable price - from 180 to 440 rubles.

Only the attending physician can prescribe this or that drug, and he also determines the dosage and duration of the therapeutic course.

Indications for use

Valparin XP is used as monotherapy or as part of complex treatment with other antiepileptic drugs for the following diseases/conditions:

generalized epileptic seizures (absences, tonic, clonic, tonic-clonic, myoclonic, atonic), Lennox-Gastaut syndrome - for the treatment of adult patients and children;
partial epileptic seizures (with or without secondary generalization) - for the treatment of adult patients and children;
bipolar affective disorders - for treatment and prevention only in adult patients.

Active substance:

Valproic acid*

Pharmgroup:

Antiepileptic drugs

Average price in pharmacies

Name	Manufacturer	average price
Valparin xr 0.3 n100 tablet prolong p/capt/coating	TORRENT PHARMA	652.00
Valparin xr 0.3 n30 tablet prolong p/capt/coating	TORRENT PHARMA	201.00
Valparin xr 0.5 n100 tablet prolong p/capt/coating	TORRENT PHARMA	1208.00
Valparin xr 0.5 n30 tablet prolong p/capt/coating	TORRENT PHARMA	389.00

Analogs for the active substance:

Valparin XP

Depakin

Depakine chrono

Depakin Chronosphere

Depakine enteric 300

Dipromal

Convulex

Convulsofin

Enkorat

Encorat chrono

Directions for use and dosage

Valparin XP is taken orally, preferably combined with meals and with a small amount of water; tablets should not be broken, crushed or chewed.

The doctor selects the dosage regimen individually, taking into account the patient’s age and body weight.

The daily dose for the treatment of well-controlled epilepsy is used in 1 dose, in other cases divided into 2 doses per day.

Recommended dosage regimen:

children over 3 years old with body weight ≥ 20 kg: initial dose – 400 mg per day, then the dose is gradually increased until optimal values are reached – usually 20–30 mg/kg per day;
adult patients: initial dose – 600 mg per day, subsequently increasing by 200 mg every 3 days until the optimal effect is obtained. The maximum recommended dose is 1000–2000 mg per day;
Elderly patients: doses recommended for adult patients are used.

Side effects

digestive system: rarely - nausea/vomiting, diarrhea/constipation, pancreatitis, hepatitis;
hypersensitivity reactions: rarely - photosensitivity, itching, skin rash, erythema multiforme, Stevens-Johnson syndrome;
central nervous system: rarely – tremor, ataxia, impaired consciousness, coma;
reproductive system: rarely - menstrual cycle disorder (MCD), secondary amenorrhea;
hematopoietic system: rarely - thrombocytopenia, anemia, neutropenia, decreased fibrinogen content, leukopenia, inhibition of platelet aggregation;
other reactions: 2–12% – alopecia; rarely – creatininemia, hyperammonemia, weight gain.

The likelihood of an overdose of valproic acid is extremely low; its symptoms are: nausea/vomiting, diarrhea, dizziness, depression of the respiratory center, hyporeflexia, coma. To treat this condition, the patient should undergo gastric lavage and give activated charcoal. If necessary, inpatient treatment of symptoms and hemodialysis are provided.

special instructions

During therapy with Valparin HR, patients are regularly examined (every 3 months), determining the activity of liver transaminases, the level of amylase, platelets and bilirubin in the blood.

Due to the inhibition of platelet aggregation by valproic acid during bleeding, the risk of increased clotting time increases. In patients receiving sodium valproate, this likelihood of complications must be taken into account in the postoperative period. As a result of prolonged therapy with valproic acid, spontaneous hematomas and bleeding may develop, which requires immediate discontinuation of the drug.

Valparin XP can cause drug-induced pancreatitis and liver failure, mainly in the first six months of use, and therefore at the beginning of treatment it is necessary to monitor the condition of the pancreas, conduct liver tests, and monitor prothrombin levels.

With the use of sodium valproate, liver dysfunction is sometimes observed in children with epilepsy in combination with degenerative and metabolic diseases, organic damage to brain tissue and mental retardation. If they observe symptoms such as vomiting, jaundice, swelling, severe weakness, lethargy, the use of the drug should be stopped immediately.

While taking Valparin XP, the patient should be careful when performing types of work that require increased concentration and speed of psychomotor reactions.

Instructions:

Clinical and pharmacological group

02.011 (Anticonvulsant)

Release form, composition and packaging

Syrup for children is colorless or slightly yellowish, with a peach aroma and a sweet peach taste.

1 ml
sodium valproate	50 mg

Excipients: sodium hydroxide, lycasin 80/55, sodium saccharin, sodium cyclamate, methylhydroxybenzoate, propylhydroxybenzoate, sodium chloride, raspberry (9/372710) and peach (9/030307) flavorings, purified water.

100 ml - dark glass bottles (1) complete with a measuring syringe - cardboard packs.

pharmachologic effect

An antiepileptic drug that has a central muscle relaxant and sedative effect. Shows antiepileptic activity in various types of epilepsy.

The main mechanism of action appears to be related to the effect of valproic acid on the GABAergic system: the drug increases the content of gamma-aminobutyric acid (GABA) in the central nervous system (CNS) and activates GABAergic transmission. Therapeutic effectiveness begins with a minimum concentration of 40-50 mg/l and can reach 100 mg/l. At a concentration of more than 200 mg/l, a dose reduction is necessary.

Pharmacokinetics

Bioavailability of the drug is about 100%. Valproic acid penetrates the cerebrospinal fluid and crosses the blood-brain barrier. T1/2 is 15-17 hours. Equilibrium concentration in plasma is achieved after 3-4 days of administration.

The binding to plasma proteins is high (90-95%), dose-dependent and saturable. It is excreted mainly in urine as a glucuronide. Valproic acid is not an inducer of enzymes of the cytochrome P450 metabolic system. Unlike most other antiepileptic drugs, it does not affect the degree of both its own biotransformation and the biotransformation of other substances, such as estrogens, progestogens and vitamin K antagonists.

Dosage

The dosage regimen is selected individually depending on the age and body weight of the patient.

The initial daily dose for adults and children weighing more than 25 kg is usually 10-15 mg/kg. Then the dose is gradually increased by 5-10 mg/kg per week until the optimal effect is achieved. The average daily dose of 30 mg/kg body weight can be increased under the control of the drug concentration in the blood plasma to 60 mg/kg.

The dose of the drug is calculated in milligrams (1 ml of the drug contains 40 mg of valproic acid). Take with meals.

It is recommended to divide the daily dose into 2-3 doses.

The solution for oral administration is available in a bottle with a measuring cap. The drug should be used using a measuring cap.

Overdose

Symptoms: nausea, vomiting, dizziness, diarrhea, respiratory dysfunction, muscle hypotonia, hyporeflexia, miosis, coma with muscle hypotonia, hyporeflexia, miosis, respiratory depression, metabolic acidosis; Cases of intracranial hypertension associated with cerebral edema have been described.

Treatment: in the hospital - gastric lavage, if no more than 10-12 hours have passed after taking the drug; monitoring the state of the cardiovascular and respiratory systems and maintaining effective diuresis. In very severe cases, dialysis is performed. The prognosis is generally good, but a few cases of death have been described.

Drug interactions

Contraindicated combinations

Mefloquine: risk of epileptic seizures in patients with epilepsy due to increased metabolism of valproic acid and the convulsant effect of mefloquine.

St. John's wort: danger of reducing the concentration of valproic acid in the blood plasma.

Combinations not recommended

Lamotrigine: increased risk of severe skin reactions including toxic epidermal necrolysis. In addition, the plasma concentration of lamotrigine increases (its metabolism in the liver is slowed down by valproic acid). If the combination is necessary, careful clinical and laboratory monitoring is required.

Combinations requiring special precautions

Carbamazepine: increased concentration of the active metabolite of carbamazepine in plasma with signs of overdose. In addition, a decrease in the concentration of valproic acid in plasma is associated with increased metabolism of valproic acid in the liver under the influence of carbamazepine. Recommended: clinical observation, determination of drug concentrations in plasma and, possibly, dose adjustment, especially at the beginning of treatment.

Carbapenems, monobactams: meropenem, panipenem, and, by extrapolation, aztreonam and imipenem: increased risk of seizures due to a decrease in the concentration of valproic acid in the blood plasma. Recommended: clinical observation, determination of drug concentrations in blood plasma; dose adjustment of valproic acid may be required during treatment with an antibacterial agent and after its discontinuation.

Felbamate: increased plasma concentrations of valproic acid with the risk of overdose. Recommended: clinical and laboratory monitoring and possible dose revision of valproic acid during treatment with felbamate and after its discontinuation).

Phenobarbital, primidone: increased plasma concentrations of phenobarbital and primidone with signs of overdose, usually in children. In addition, a decrease in the concentration of valproic acid in plasma associated with increased hepatic metabolism under the influence of phenobarbital or primidone. Recommended: clinical monitoring during the first 15 days of combination treatment with immediate reduction of the dose of phenobarbital or primidone at the first signs of sedation, determination of blood concentrations of both anticonvulsants.

Phenytoin: changes in the concentration of phenytoin in plasma, the risk of a decrease in the concentration of valproic acid associated with increased metabolism of valproic acid in the liver under the influence of phenytoin. Recommended: clinical monitoring with determination of plasma concentrations of both antiepileptic drugs and, if necessary, adjustment of their doses.

Topiramate: Risk of hyperammonemia or encephalopathy. Recommended: clinical and laboratory monitoring during the first month of treatment and in case of symptoms of ammonemia.

Neuroleptics, monoamine oxidase inhibitors (MAO inhibitors), antidepressants, benzodiazepines: Valproic acid potentiates the effect of psychotropic drugs such as neuroleptics, MAO inhibitors, antidepressants, benzodiazepines. Recommended: clinical monitoring and, if necessary, dose adjustment of the drug.

Cimetidine and erythromycin: the concentration of valproic acid in the blood plasma increases.

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

Combinations to Consider

Nimodipine (oral and, by extrapolation, parenteral): increased hypotensive effect of nimodipine due to a decrease in its metabolism under the influence of valproic acid and increased concentration in the blood plasma.

Acetylsalicylic acid: increased effects of valproic acid due to an increase in its concentration in the blood plasma.

When used simultaneously with anticoagulants, vitamin K antagonists require careful monitoring of the prothrombin index.

Other forms of interaction

Valproic acid does not have an enzyme-inducing effect and therefore does not affect the effectiveness of hormonal contraceptives containing combinations of estrogen and progesterone.

Use during pregnancy and lactation

Animal studies have shown teratogenic effects.

According to available data, in humans, valproic acid predominantly causes disturbances in the development of the neural tube: myelomeningocele, spina bifida (1-2%). Cases of facial dysmorphia and malformations of the limbs (especially shortened limbs), as well as malformations of the cardiovascular system, have been described.

The risk of developmental defects is higher with combination antiepileptic therapy than with valproic acid monotherapy.

Considering the above, during pregnancy the use of the drug is possible only if the expected benefit to the mother outweighs the potential risk to the fetus. During pregnancy, antiepileptic treatment with valproic acid should not be interrupted if it is effective. In such cases, monotherapy is recommended; The minimum effective daily dose should be divided into two doses.

In addition to antiepileptic therapy, folic acid preparations (at a dose of 5 mg/day) can be added, because they help minimize the risk of neural tube malformations.

Valproic acid can cause hemorrhagic syndrome in newborns, which appears to be associated with hypofibrinogenemia. Cases of afibrinogenemia with fatal outcomes have been reported. This may be due to a decrease in a number of blood clotting factors.

In a newborn, it is necessary to determine the number of platelets, the level of fibrinogen in plasma and blood clotting factors.

Valproic acid is excreted in breast milk in concentrations ranging from 1% to 10%. It is recommended to stop breastfeeding while taking the drug.

Side effects

From the central nervous system: ataxia; cases of cognitive impairment with a progressive onset until the development of a full picture of dementia syndrome (reversible within several weeks or months after discontinuation of the drug); states of confusion or convulsions; stupor or lethargy, sometimes leading to transient coma (encephalopathy); reversible parkinsonism; headache, dizziness, mild postural tremor and drowsiness, changes in behavior, mood or mental state (depression, fatigue, hallucinations, aggressiveness, hyperactivity, psychosis, unusual agitation, restlessness or irritability), dysarthria.

From the digestive system: often at the beginning of treatment - gastrointestinal disorders (nausea, vomiting, gastralgia, decreased appetite or increased appetite, diarrhea), which usually disappear within a few days without stopping the drug; liver dysfunction; 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 hemostatic system: inhibition of bone marrow hematopoiesis (anemia, leukopenia or pancetopinia); 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.).

From the urinary system: enuresis; cases of reversible Fanconi syndrome (of unknown origin).

From the endocrine system: dysmenorrhea, secondary amenorrhea, enlarged mammary glands, galactorrhea.

Allergic reactions: skin rash, urticaria, vasculitis; angioedema, photosensitivity, cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme.

Laboratory indicators: isolated and moderate hyperammonemia without changes in liver function tests, especially with polytherapy (drug discontinuation is not required); possible hyperammonemia associated with neurological symptoms (further evaluation required); possible increase in the activity of “liver” transaminases; decreased fibrinogen content or increased bleeding time, usually without clinical manifestations and especially at high doses (valproic acid has an inhibitory effect on the second stage of platelet aggregation); hyponatremia.

Other: teratogenic risk; diplopia, nystagmus, flashing spots before the eyes, alopecia; reversible or irreversible hearing loss; peripheral edema; weight gain; menstrual irregularities, amenorrhea, immune system disorders.

Storage conditions and periods

Store at a temperature not exceeding 30°C in a place protected from light. Keep out of the reach of children.

Best before date. 2 years. Do not use after the expiration date indicated on the package.

Indications

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

- treatment of generalized epileptic seizures (clonic, tonic, tonic-clonic, absence seizures, myoclonic, atonic); Lennox-Gastaut syndrome;

- treatment of partial epileptic seizures (partial seizures with or without secondary generalization);

— treatment and prevention of bipolar affective disorders.

In children, as monotherapy or in combination with other antiepileptic drugs:

- treatment of generalized epileptic seizures (clonic, tonic, tonic-clonic, absence seizures, myoclonic, atonic); Lennox-Gastaut syndrome;

- treatment of partial epileptic seizures (partial seizures with or without secondary generalization).

Contraindications

Hypersensitivity to valproic acid or other components of the drug; acute hepatitis; chronic hepatitis; history of liver disease, porphyria; combination with mefloquine; combination with St. John's wort; not recommended for use in combination with lamotrigine.

Carefully. 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.

special instructions

Before starting treatment and during the first 6 months of therapy, periodic monitoring of liver function is necessary, especially in patients at risk.

Among the classical tests, the most important are those reflecting protein synthesis in the liver and especially the prothrombin index. If there is a significant decrease in the concentration of prothrombin, a marked decrease in the content of fibrinogen, blood clotting factors, an increase in the concentration of bilirubin and transaminase activity, treatment with Valparin® should be suspended. If the patient is receiving salicylates at the same time, they should also be immediately discontinued, since salicylates and valproic acid have common metabolic pathways.

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

Early diagnosis is based primarily on clinical examination. In particular, two factors that may precede jaundice should be taken into account, especially in patients at risk:

- nonspecific general symptoms, usually appearing suddenly, such as asthenia, anorexia, extreme fatigue, drowsiness, sometimes accompanied by repeated vomiting and abdominal pain;

- recurrence of epileptic seizures during antiepileptic therapy.

The patient, and if it is a child, then his family, should be warned about the need to immediately notify the doctor about the occurrence of these symptoms. In addition to clinical examination, liver function testing should be performed immediately in such cases.

In rare cases, severe forms of pancreatitis have been reported, sometimes with death. These cases were observed regardless of the patient's age and duration of treatment, although the risk of developing pancreatitis decreased with increasing age of the patients. Insufficiency of liver function in pancreatitis increases the risk of death.

It should be emphasized that during treatment with both Valparin® and other antiepileptic drugs, a slight, isolated and temporary increase in the activity of liver transaminases may be observed, especially at the beginning of treatment, in the absence of any clinical symptoms. In this case, it is recommended to conduct a more complete examination (including, in particular, determination of the prothrombin index) in order to revise the dose if necessary and repeat the tests depending on changes in parameters.

Before starting therapy, before surgery, if hematomas or spontaneous bleeding occur, a general blood test (including determination of platelet count, bleeding time and coagulogram parameters) is required.

If symptoms of an “acute” abdomen and gastrointestinal symptoms such as nausea, vomiting and/or anorexia occur during treatment, it is necessary to determine the activity of amylase in the blood to exclude acute pancreatitis. If the activity of pancreatic enzymes is increased, the drug should be discontinued and alternative therapeutic measures taken.

When using Valparin® in patients with renal failure, it is recommended to take into account the increased concentration of the free form of valproic acid in the blood plasma and reduce the dose.

If it is necessary to prescribe the drug to patients with systemic lupus erythematosus and other diseases of the immune system, the expected therapeutic effect and the possible risk of therapy should be assessed, since disorders of the immune system have been observed in extremely rare cases when using Valparin®.

It is not recommended to prescribe the drug to patients with carbamide cycle enzyme deficiency. In such patients, several cases of hyperammonemia accompanied by stupor and/or coma have been described.

During treatment, drinking drinks containing ethanol is not allowed.

Patients should be warned of the risk of weight gain early in treatment and advised to follow a diet to minimize this effect.

Influence on the ability to drive vehicles and operate machinery. During the treatment period, patients must be careful when driving vehicles and other activities that require high concentration and speed of psychomotor reactions.

Use for renal impairment

With caution: renal failure. When using Valparin® in patients with renal failure, it is recommended to take into account the increased concentration of the free form of valproic acid in the blood plasma and reduce the dose.

Use for liver dysfunction

Contraindicated: acute hepatitis; chronic hepatitis; history of liver disease.