Valprocom 300 Chrono 100 tablets — Made in Ukraine — Free Delivery

(Valprocom 300 Chrono )
Valprocom 300 Chrono 100 tablets — Made in Ukraine — Free Delivery
Availability: In Stock
Acino Brand: Acino

Coupon code -5%: BONUS23

You can apply the coupon in the shopping cart at checkout.

 

Description Valprocom 300 Chrono 100 tablets — Made in Ukraine — Free Delivery

Pharmacological properties

Pharmacodynamics. Long-acting anticonvulsant preparation. inhibits gamma transferase, inhibits the biotransformation of gamma (inactivation), stabilizes and increases its content in the central nervous system. stimulates the central gamko-ergic processes (including inhibitory stress-limiting ones), reduces the excitability and convulsive readiness of the motor zones of the brain.

Shows tranquilizing properties, reduces the feeling of fear, improves the mental state and mood of patients. Highly effective for absences and temporal pseudoabsances, ineffective for psychomotor seizures.

It is known that in pharmacological studies, valproate inhibited various experimentally induced seizures (generalized and focal). Similarly, in humans, the antiepileptic effect of valproate can also be observed in different types of epilepsy.

In some in vitro studies, valproate has been observed to stimulate HIV-1 replication. However, this effect is not particularly pronounced and is not reproducible in all experiments. The clinical implications of this observation in HIV-1 infected patients are unknown. These data should be considered when evaluating viral load measurements during the use of sodium valproate in HIV-1-infected patients.

Pharmacokinetics

Suction. The bioavailability of the preparation is about 100%.

Valprokom Chrono is present in the blood as valproic acid.

Valprokom Chrono is immediately absorbed into the gastrointestinal tract. Its absorption is permanent and long lasting. Therefore, there are no peaks in plasma preparation concentration, and therapeutic valproic acid concentrations are better maintained over time.

Distribution. The volume of distribution of valproic acid is predominantly limited by blood and extracellular fluid, which undergoes rapid exchange.

Binding to blood proteins occurs mainly with albumin and is dose-dependent and saturated. With a total concentration of valproic acid in blood plasma of 40–100 mg / l, part of its free fraction is predominantly 6–15%.

The level of valproic acid in the CSF is similar to the concentration of its unbound substance in the blood plasma (approximately 10%).

Valproic acid is excreted during dialysis, but the volume of the excreted fraction is significantly reduced as a result of its binding with albumin (approximately 10%).

The therapeutic efficacy of the preparation is manifested when its concentration in blood plasma is 40–100 mg / l (278–694 µmol / l). With regular intake of the preparation Valprocom Chrono, the equilibrium concentration is established on the 3-4th day of therapy, in some cases - after a longer period. In the case of maintaining the total level of valproic acid in the blood plasma of 150 mg / l (1040 μmol / l), a decrease in the daily dose is necessary. More than 96% of the preparation undergoes intensive metabolism in the liver, 90-95% binds to blood plasma proteins, mainly albumin. The preparation penetrates the BBB, the placental barrier, when using the preparation Valprokom Chrono women who are breastfeeding, valproic acid is excreted in breast milk (1-10% of the total concentration in blood plasma).

Metabolism. The metabolism of the preparation Valprocom Chrono occurs predominantly in the liver. The main metabolic pathways are glucuronic acid conjugation and β-oxidation. Unlike most other antiepileptic preparations, sodium valproate does not accelerate its own degradation or the degradation of other substances, such as estrogen-progestogens. This feature indicates that it does not induce enzymes included in the metabolic system of cytochrome P450.

Excretion. For a long time, the average T½ of valproic acid from blood plasma in adults is 10.6 hours (but can vary from 5 to 20 hours), which is the basis for a dosing regimen 2 times a day.

In full-term infants, T½ is 20-30 hours. However, it is rapidly approaching adult values ​​as the infant grows.

Valproic acid is excreted primarily by the kidneys.

A small fraction remains unchanged, but most is determined in the urine as metabolites.

Pharmacokinetics of certain groups of patients

In patients with renal impairment. The level of binding to albumin is reduced. Thus, one should take into account the increase in the free fraction of valproic acid in the blood plasma, which is a consequence of this, and accordingly reduce the dose.

In elderly patients. Changes in pharmacokinetic parameters were revealed, but they turned out to be insignificant.

Thus, the patient's clinical response (seizure control) was decisive for dose selection.

Indications

The main indication for the use of Valprocom Chrono, preferably as a monotherapy, is primary generalized epilepsy: minor epileptic seizures / absence epilepsy, massive bilateral myoclonic seizures, major epileptic seizures with or without myoclonus, photosensitive forms of epilepsy.

Also, as monotherapy or in combination with other antiepileptic preparations, it is effective for the following diseases:

  • secondary generalized epilepsy, especially West syndrome (convulsions in young children) and Lennox-Gastaut syndrome;
  • partial epilepsy with simple or complex symptoms (psychosensory forms, psychomotor forms);
  • epilepsy with secondary generalization;
  • mixed forms of epilepsy (generalized and partial).

Treatment of episodes of mania associated with bipolar disorder, in the presence of contraindications to the use of or intolerance to lithium.

Prevention of recurrence of dysthymic episodes in adult patients with bipolar disorder who have a therapeutic response to valproate therapy during the treatment of manic episodes.

Application

Valprokom Chrono is a form of the preparation with a delayed release of the active substance, which allows to reduce the maximum and provides a more uniform concentration of the active substance in the blood plasma throughout the day. the preparation is taken orally, preferably with meals. the daily dose is recommended to be taken in 1 or 2 doses. single use is possible in case of well-controlled epilepsy. swallow the tablet whole, without crushing or chewing, with half a glass of water, milk or other non-alcoholic drink. due to the process of prolonged release of the preparation and the type of excipients in the composition of the preparation, the inert matrix is ​​not absorbed into the gastrointestinal tract, it is excreted during the bowel movement after the release of the active substance.

Epilepsy

The usual dose. The daily dose is determined according to the age and body weight of the patient. However, it should be borne in mind that the range of individual sensitivity to valproate is quite wide. The optimal dose is adjusted according to the clinical response obtained. In case of unsatisfactory control of seizures or if there is a suspicion of the possibility of developing adverse reactions, it may be necessary, in addition to clinical observation, to determine the concentration of the preparation in the blood plasma.

A concentration range of 40–100 mg / l (300–700 µmol / l) is considered therapeutic.

First line monotherapy. Thanks to the Chrono dosage form (prolonged action), the daily dose of the preparation can be used at one time. The preparation should be taken at the beginning of a meal.

Most often, the following daily doses should be used:

25 mg / kg - for children;

20-25 mg / kg - for adolescents;

20 mg / kg - for adults;

15–20 mg / kg - for elderly patients.

If possible, therapy with Valprocom Chrono should be started gradually.

The initial daily dose of valproate is 10-15 mg / kg, then the dose should be gradually increased until the optimal dose is reached.

If the patient is not taking any other antiepileptic preparations, the dose should be increased gradually at intervals of 2-3 days to reach the optimal dose in about a week.

For patients taking other anticonvulsants, treatment with Valprocom Chrono should be started gradually in order to achieve a clinically effective dose within about 2 weeks, after which, depending on the effectiveness of treatment, the doses of preparations taken simultaneously should be reduced.

The observation phase can be initiated if, when using the preparation  as monotherapy, the following doses are achieved: 15 mg / kg / day in elderly patients, 20 mg / kg / day in adults and adolescents, and 25 mg / kg / day in children and infants.

If clinical efficacy is satisfactory, the dose achieved should be maintained at this level. Daily doses of 25 mg / kg in elderly patients, 30 mg / kg in adults and adolescents, and 25 mg / kg in children and infants, especially when using valproate as monotherapy, are rarely necessary.

If these doses still do not allow seizure control to be achieved, you can continue to increase the doses.

If the daily dose exceeds 50 mg / kg, it is recommended to divide it into 3 doses, while additional clinical examinations and monitoring of indicators of a biochemical blood test are required (see SPECIAL INSTRUCTIONS). If it is necessary to use a combination of the preparation Valprocom Chrono with other antiepileptic preparations, they should be introduced into the treatment regimen gradually.

The use of the preparation Valprocom Chrono in combination with other antiepileptic preparations. Start the administration of sodium valproate in the same way as with first-line monotherapy. The average daily dose is usually identical to the recommended dose for monotherapy. However, in some cases, this dose may be increased by 5-10 mg / kg. You should also take into account the effect of the preparation Valprokom Chrono on other antiepileptic preparations.

Replacing another antiepileptic preparation  with Valprocom Chrono. If you plan to gradually and completely replace the previous preparation  with Valprokom Chrono, then it must be used according to the recommendations for first-line monotherapy. The dose of certain previous medications, especially barbiturates, should be gradually reduced immediately over 2-8 weeks until complete withdrawal.

Episodes of mania in patients with bipolar disorder. The recommended starting dose is 20 mg / kg / day. This dose must be increased as quickly as possible until the minimum therapeutic dose is reached, allowing the desired clinical effect to be obtained.

As a rule, the desired clinical effect is achieved at a plasma valproate concentration of 45–125 μg / ml.

The dose can be adjusted depending on the individual clinical response. The maximum dose should not exceed 3000 mg / day.

The recommended maintenance dose for bipolar disorders is 1000–2000 mg / day.

Children and adolescents: the efficacy and safety of Valprokom 500 Chrono for the treatment of episodes of mania associated with bipolar disorders have not been studied.

Prevention of relapse of episodes of mania that accompany bipolar disorder. The dose for the prevention of relapse is the lowest effective dose to adequately control the symptoms of acute mania in a given patient. The maximum daily dose of 3000 mg should not be exceeded.

Female children, female adolescents, women of reproductive age and pregnant women. Therapy with the preparation  must be started and carried out under the supervision of a specialist with experience in the treatment of epilepsy. Treatment with this preparation should be prescribed only if other types of therapy are ineffective or not tolerated by patients (see SPECIAL INSTRUCTIONS and Use during pregnancy and lactation); the benefits and risks of using this preparation must be carefully reassessed when evaluating treatment regularly. As a rule, the preparation Valprocom Chrono is prescribed as monotherapy in the lowest dose at which the effect of treatment is observed and, if possible, in the form of a dosage form with prolonged release to avoid high peak concentrations in blood plasma. The daily dose must be divided into at least two doses.

Valprokom 300 Chrono :. In patients under the age of 18 years, the effectiveness and safety of the preparation for the treatment of manic episodes associated with bipolar disorder has not been evaluated.

Valprokom 500 Chrono. The preparation is prescribed for children weighing 17 kg. This dosage form is not recommended for use in children under 6 years of age (there is a risk of entering the respiratory tract if swallowed).

Children under 3 years of age are recommended to use valproate as monotherapy, but before starting treatment, the therapeutic benefit of valproate should be carefully evaluated in relation to the risk of liver damage or the development of pancreatitis (see SPECIAL INSTRUCTIONS).

It is necessary to avoid the simultaneous use of salicylates for the treatment of children under the age of 3 years because of the risk of developing hepatotoxicity.

Contraindications

A history of hypersensitivity to valproate, divalproate, valpromide or other components of the preparation. acute hepatitis. chronic hepatitis. cases of severe hepatitis in an individual or family history of the patient, especially caused by preparations. hepatic porphyria. combination with mefloquine and St. John's wort preparations (see interactions). valproate is contraindicated in patients with known mitochondrial disorders caused by mutations in the nuclear gene that encodes the mitochondrial enzyme gamma polymerase (polg), for example with Alpers-Guttenlocher syndrome, children under 2 years of age suspected of having a polg-related disorder, and patients with violation of the ornithine cycle in history (see special instructions).

Side effects

Adverse reactions are classified depending on the frequency of development: very often (≥1 / 100, 1/10); often (≥1 / 100, 1/10); infrequently (≥1 / 1000, 1/100); rarely (≥1 / 10,000, 1/1000); very rare (≥1 / 10,000); frequency unknown (cannot be estimated from existing data).

Congenital, familial and genetic disorders (see Use during pregnancy and lactation)

From the digestive system: very often - nausea; often - vomiting, gum disease (mainly gingival hyperplasia), stomatitis, epigastric pain, diarrhea and other dyspeptic disorders often appear at the beginning of treatment and, as a rule, go away on their own within a few days without discontinuing the preparation. The incidence of these disorders can be significantly reduced by increasing the dose of Valprokom Chrono very slowly, by taking film-coated, sustained-release tablets (Chrono) and taking the preparation at the beginning of a meal. In these cases, symptomatic therapy may be prescribed. Uncommon - cases of pancreatitis that require early withdrawal of the preparation.

The consequences can sometimes be fatal (see SPECIAL INSTRUCTIONS).

All patients who complain of acute abdominal pain while taking sodium valproate / valproic acid should immediately undergo a medical examination (analysis of pancreatic enzymes, other appropriate laboratory tests).

Hepatobiliary disorders: often - impaired liver function (transient increase in the level of hepatic transaminases and the level of bilirubin in the blood plasma) (see SPECIAL INSTRUCTIONS).

Cases of severe liver damage including liver failure, sometimes with fatal consequences, have been reported. Increased liver enzymes, especially at the beginning of therapy, usually transient.

From the respiratory system, chest and mediastinal organs: infrequently - pleural effusion.

Mental disorders: very often - confusion, aggression *, irritability, impaired attention *, hallucinations, irritability *; rarely - abnormal behavior *, psychomotor hyperactivity *, learning difficulties *.

* These effects are seen predominantly in children.

From the side of the central nervous system: very often - tremor; often - drowsiness, headache, nystagmus, extrapyramidal disorders (sometimes irreversible), stupor *, convulsions *, memory impairment, dizziness (in the case of intravenous injection, dizziness occurs a few minutes after the injection and, as a rule, spontaneously disappears a few more minutes); infrequently - paresthesia, ataxia, small-amplitude postural tremor (primarily of the upper extremities, it may be temporary, dose reduction may be necessary), isolated reversible parkinsonism, isolated stupor states, lethargy, sometimes leading to transient coma (encephalopathy), isolated or in combination with a paradoxical increase in seizures ending after discontinuation or dose reduction. Such cases more often occur during therapy with several preparations (in particular with phenobarbital or topiramate) or after a sharp increase in the dose of valproate. Rare - Very rare cases of cognitive impairment with gradual onset and progressive development have been described, which can progress to complete dementia and are reversible, disappearing after stopping treatment for a period of several weeks to several months; very rarely - confusion.

Several cases of hyperactivity and irritability have been reported at the start of treatment, mainly in children.

Cases of sedation have been reported (especially when taken with other anticonvulsants). There have also been reports of cases of reversible Parkinson's syndrome, which were rarely noted.

On the part of the organs of hearing and balance: often - deafness (sometimes irreversible); frequency unknown - tinnitus / ringing.

On the part of the hematopoietic system: often - anemia, thrombocytopenia (usually asymptomatic, in which, if possible, a decrease in the dose of the preparation  is shown, taking into account the level of platelets and the degree of control of the disease, which usually contributes to the disappearance of thrombocytopenia); infrequently - pancytopenia, leukopenia; rarely - macrocytosis, macrocytic anemia, red bone marrow aplasia or true erythrocytic aplasia; agranulocytosis.

Cases of a decrease in fibrinogen levels or an increase in the duration of bleeding have been reported (especially with high doses of the preparation), usually without clinical consequences. Valproate inhibits the second phase of platelet aggregation.

Aplasia of the red bone marrow or true erythrocytic aplasia.

There is information on blood sedimentation disorders consistent with type I von Willebrand disease.

A blood test (CBC including platelet count, bleeding time, and blood sedimentation tests, including factor VIII) should be performed before starting therapy, and if the patient is planning surgery or if hematoma or spontaneous bleeding.

From the side of the vessels: often - bleeding; infrequently - vasculitis.

From the genitourinary system: infrequently - renal failure, kidney damage; rarely - enuresis, urinary incontinence, tubulointerstitial nephritis, reversible Fanconi syndrome, but the mechanism of action has not yet been clarified.

On the part of the skin and subcutaneous tissue: often - hypersensitivity reactions, transient and / or dose-dependent alopecia, damage to the nails and nail bed; infrequently - angioedema, rash, hair problems (for example, abnormal hair texture, changes in hair color, abnormal hair growth); rarely toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, preparation hypersensitivity syndrome, or DRESS syndrome (preparation rash syndrome with eosinophilia and systemic symptoms).

From the musculoskeletal system: infrequently - a decrease in bone mineral density, osteopenia, osteoporosis, fractures in patients on long-term therapy with valproate; rarely - systemic lupus erythematosus, rhabdomyolysis.

Metabolic and alimentary disorders: often - increased appetite and weight gain (in 5-10% of patients), in particular in adolescents and young women. Since an increase in body weight can lead to a worsening of the clinical symptoms of polycystic ovary syndrome (see SPECIAL INSTRUCTIONS), body weight must be monitored; hyponatremia. Rarely - isolated and moderately severe hyperammonemia without changes in liver function indicators, especially with multiple preparation therapy, and this should not lead to discontinuation of treatment. Cases of hyperammonemia with neurological symptoms have also been described. In such cases, additional research is necessary (see also SPECIAL INSTRUCTIONS).

Endocrine disorders: infrequently - syndrome of inadequate secretion of antidiuretic hormone, hyperandrogenism (hirsutism, virilism, acne, androgenic alopecia and / or increased levels of androgenic hormones); rarely - hypothyroidism (see. Application during pregnancy and lactation).

Reproductive disorders: often - dysmenorrhea, menstrual irregularities; infrequently - amenorrhea; rarely - the risk of polycystic ovarian syndrome, infertility in men; very rarely - gynecomastia.

Benign, malignant and undiagnosed neoplasms (including cysts and polyps): rarely - myelodysplastic syndrome.

Disorders associated with pregnancy and the puerperium and perinatal disorders. Impaired intellectual development after intrauterine exposure to valproate (see Use during pregnancy and lactation and SPECIAL INSTRUCTIONS).

General disorders. Cases of hypothermia have been reported. Very rarely, cases of mild peripheral edema have been reported.

Research results: rarely - a decrease in the content of blood coagulation factors, deviations from the norm on the part of coagulation indicators (such as an increase in prothrombin time, an increase in activated partial thromboplastin time, an increase in thrombin time, an increase in the international normalized ratio). While using the preparation Valprocom Chrono, the number of platelets may decrease by 10,000-30,000 / mm3. In most cases, this decrease is dose-dependent and transient. In this regard, it is recommended to determine the number of platelets before and 3 and 6 months after the start of treatment, as well as before surgery, especially if the dose exceeds 30 mg / kg / day. Rarely - deficiencies of biotin / biotinidase enzymatic activity.

Teratogenic risk (see Use during pregnancy and lactation).

Special instructions

The beginning of the use of an antiepileptic preparation can sometimes be accompanied by the resumption of epileptic seizures or the occurrence of more severe seizures or the development of new types of seizures in the patient, regardless of the spontaneous fluctuations that are observed in some epileptic conditions. first of all, this can be observed with changes in the combination therapy with antiepileptic preparations and may be associated with pharmacokinetic interactions, toxicity or overdose.

Sodium valproate, which is one of the active substances of the preparation Valprocom Chrono, is converted into valproic acid in the human body, therefore, other preparations that undergo the same transformation should not be used simultaneously in order to avoid an overdose of valproic acid (for example, divalproate, valpromide).

Female children / female adolescents / women of reproductive age / pregnant women. Due to the high teratogenic potential and the risk of developmental disorders in infants who have been exposed to intrauterine exposure to valproate, Valprocom Chrono should not be used in female children, adolescents, women of reproductive age and pregnant women, unless alternative treatments are ineffective. or are not tolerated by patients. The benefits and risks of using this preparation should be carefully reviewed with regular evaluation of treatment, during puberty and immediately when a woman of reproductive age taking Valprokom Chrono is planning a pregnancy or has already become pregnant. Women of reproductive age should use effective contraception during treatment with this preparation and should be informed about the risks associated with the use of Valprocom Chrono during pregnancy (see Use during pregnancy and lactation).

In particular, the prescribing physician must ensure that the patient understands:

  • the essence and importance of the risks associated with the effect of the preparation during pregnancy, in particular teratogenic risks and risks of developmental disorders;
  • the need to use effective contraception;
  • the need for regular evaluation of treatment;
  • the need for immediate medical attention in case of planning or probable pregnancy.

If possible, all measures should be taken to replace the preparation in women planning pregnancy with an appropriate alternative treatment before fertilization (see Use during pregnancy and lactation).

Treatment with valproate can only be continued after reevaluation by a physician who has experience in the treatment of epilepsy, the benefits and risks of such therapy for the patient.

Severe liver damage

Conditions of occurrence. There are isolated reports of severe or sometimes fatal liver damage. Experience shows that the greatest risk, especially in the case of concomitant use of other antiepileptic preparations, is observed in infants and children under 3 years of age with severe epilepsy, in particular, this applies to children with brain damage, mental retardation and / or genetically determined metabolic or degenerative diseases.

In children aged 3 years and older, the risk decreases significantly, which gradually decreases with age.

In most cases, such liver damage was detected during the first 6 months of treatment, usually within 2–12 weeks, and most often - in complex antiepileptic therapy.

It is recommended to inform the patient (if the child is his parents) that when the described clinical symptoms appear, you should immediately consult a doctor. In addition to clinical examination, functional liver function tests are urgently needed.

Signs to watch out for. An early diagnosis of hepatotoxicity is clinical. In particular, symptoms that may precede jaundice and other symptoms suggestive of hepatotoxicity should be considered:

General symptoms and signs (usually onset): for example, drowsiness, asthenia, confusion, restlessness, anorexia, abdominal pain, vomiting, bleeding and swelling

relapse of epileptic seizures: despite following the doctor's instructions.

Revealing. Liver function tests should be performed prior to initiation of therapy and then performed regularly during the first 6 months of treatment. During therapy, it is necessary to regularly monitor liver function tests (level of aminotransferases, bilirubin, total protein), blood clotting (prothrombin time, fibrinogen, factor VIII), platelet count, lipase and alpha-amylase activity in urine. If an abnormally low level of prothrombin is detected, especially accompanied by a significant decrease in the level of fibrinogen and blood clotting factors, an increase in the level of bilirubin and transaminases, treatment with valproate should be suspended. The risk of developing side effects from the liver is increased with combination therapy with other antiepileptic preparations.

As a precautionary measure, as well as with simultaneous use, therapy with salicylates should be discontinued, since they have the same metabolic pathway. Laboratory tests should be repeated depending on the identified changes in indicators.

Pancreatitis Rarely, cases of pancreatitis have been reported, which are sometimes fatal. These cases did not depend on the patient's age and the duration of treatment. Pancreatitis most often occurs in young children or in patients with severe epilepsy, brain damage, or in patients taking complex antiepileptic therapy. If pancreatitis is accompanied by liver failure, the risk of death increases significantly.

In patients with acute abdominal pain or gastrointestinal symptoms such as nausea, vomiting and / or anorexia, differential diagnosis with pancreatitis should be made and, if transaminase levels are elevated, the preparation should be discontinued immediately and alternative therapeutic measures should be resorted to.

The patient and / or family should seek immediate medical attention if symptoms of pancreatitis appear (such as abdominal pain, nausea and vomiting). If there are symptoms suggestive of pancreatitis, a medical examination should be carried out, including the determination of the level of lipase and / or amylase in the blood plasma. If you suspect pancreatitis, the use of 

Valprocom Chrono should be discontinued immediately.

As a precautionary measure, given the risk of hepatotoxicity, salicylic acid derivatives should not be used concomitantly with this preparation.

In children under the age of 3 years, the preparation  Valprocom Chrono should be used only as monotherapy. In patients of this age group, therapy should be started only after evaluating the clinical benefits and risks of liver damage or the development of pancreatitis. However, salicylates should not be used in children under 16 years of age (see background information on acetylsalicylic acid / salicylates in Reye's syndrome).

In children with unexplained symptoms of the liver and digestive tract (anorexia, vomiting, cases of cytolysis), lethargy or coma in history, with mental retardation, in case of death in an infant or child in a family history, before starting treatment with Valprok, Chrono should be performed metabolic studies, especially the fasting and postprandial ammonia test.

It is necessary to control the free concentration of valproic acid in the blood of patients with renal failure and, if it rises, reduce the dose of the preparation accordingly.

Sodium valproate increases the risk of hyperammonemia in patients with impaired urea cycle. The use of sodium valproate in such patients should be avoided. In such patients, cases of hyperammonemia, accompanied by stupor or coma, have been described. Although in the course of treatment with valproate, violations of the functions of the immune system are extremely rare, the possible benefits of using the preparation 

Valprocom Chrono  must be compared with the potential risk when prescribing the preparation to patients with systemic lupus erythematosus.

Before starting therapy or surgery, in the case of spontaneous hematomas or bleeding, it is recommended to conduct a blood test (determine the blood formula, including platelet count, bleeding time and coagulation tests).

Before starting treatment, patients should be warned about the possibility of an increase in body weight, which can be a risk factor for the development of polycystic ovary syndrome in women. Therefore, the body weight of patients should be carefully monitored, it is necessary to take appropriate measures, mainly of a dietary nature, to minimize this phenomenon.

Violation of intellectual development (see Use during pregnancy and lactation and SIDE EFFECTS).

Clinical evidence suggests that children exposed to intrauterine valproate have a higher risk of impaired intellectual development.

Suicidal thoughts and behavior. Cases of suicidal thoughts and behavior have been reported in patients treated with antiepileptic preparations for multiple indications.

A meta-analysis of randomized, placebo-controlled clinical trials of antiepileptic preparations found a slight increase in the risk of suicidal thoughts and behavior. The mechanism of this increase is unknown, and the available data do not exclude the possibility of an increase in the risk of suicide when taking Valprocom Chrono. Patients should be closely monitored for early signs of depression, self-harm, suicidal thoughts or behavior. Patients (and their caregivers) should be warned to seek immediate medical attention if they show signs of suicidal thoughts or behavior. Patients with concomitant carnitine palmitoyltransferase type II deficiency should be advised of an increased risk of rhabdomyolysis while taking valproate.

Effect of long-term treatment on bone metabolism. Cases of a decrease in bone mineral density, which may indicate the presence of osteopenia or osteoporosis, and even lead to the occurrence of atypical fractures, have been reported in patients who underwent long-term treatment with valproic acid. The mechanism of action of valproic acid on bone metabolism has not yet been elucidated (see SIDE EFFECTS).

Carbapenems. Concomitant use of the preparation Valprocom Chrono and carbapenems is not recommended (see INTERACTIONS).

Patients with known or suspected mitochondrial disease. Valproate can provoke or worsen the clinical signs of existing mitochondrial diseases caused by mutations in mitochondrial DNA, as well as the nuclear gene encoding the mitochondrial enzyme POLG.

In particular, in patients with hereditary neurometabolic syndromes caused by mutations in the POLG gene (for example, with Alpers-Gutenlocher syndrome), cases of acute hepatic failure caused by valproate and deaths due to impaired liver function have been reported. POLG-related disorders should be suspected in patients with a family history of POLG-related disorders or symptoms suggestive of such a disorder, including, but not limited to, encephalopathy of unexplained origin, refractory epilepsy (focal, myoclonic), epileptic status, developmental delay, regression of psychomotor functions, axonal sensorimotor neuropathy, myopathy, cerebellar ataxia, ophthalmoplegia, or complicated migraine with occipital aura.

Tests for the presence of POLG mutations should be performed in accordance with current clinical practice for the diagnostic evaluation of such disorders (see CONTRAINDICATIONS).

Influence on diagnostic methods. Since sodium valproate is excreted in the urine in part in the form of ketones, it can cause pseudo-positive results when urine is tested for the presence of acetone.

Alcohol. During treatment with Valprocom Chrono, alcohol consumption is contraindicated.

Use during pregnancy and lactation. Valprokom Chrono should not be used in female children, female adolescents, women of reproductive age and pregnant women, unless other methods of treatment are ineffective or are not tolerated by patients. Women of reproductive age should use effective contraception during treatment with this preparation. Whenever possible, all measures should be taken to replace the preparation in women planning to become pregnant with an appropriate alternative treatment before fertilization.

Risks associated with exposure to valproate during pregnancy. Both valproate monotherapy and valproate-containing polytherapy have been associated with negative pregnancy outcomes. Available data indicate that antiepileptic polytherapy, one of the preparations of which is valproate, is associated with a higher risk of congenital malformations than monotherapy with valproate, 3-4 times higher than in the general population (approximately 3%).

Congenital malformations. It was reported that a meta-analysis that included registry and cohort studies showed that 10.73% of children born to women with epilepsy who received valproate monotherapy during pregnancy had congenital malformations (95% CI 8.16 –13.29). This risk of the most common malformations is higher than in the general population, where the risk is approximately 2-3%. This risk is dose-dependent, however, it is not possible to establish dose limit values ​​below which there is no risk. Available data indicate an increased incidence of rare and frequent malformations.

The most common defects associated with impaired closure of the embryonic neural tube (approximately 2-3%): myelomeningocele, spina bifida, which can be diagnosed in the prenatal period; dysmorphia of the face, cleft lip and palate, craniostenosis, malformations of the heart and organs of the genitourinary system (especially hypospadias), limb defects (including bilateral aplasia of the radius) and multiple anomalies of various body systems.

A special prenatal examination of the patient is necessary in order to identify violations of the neural tube infection or other anomalies in the development of the fetus during the first months of pregnancy. The most important risk factors for the occurrence of adverse congenital malformations were the intake of valproate in doses exceeding 1000 mg / day, and the combined use with other anticonvulsants.

Developmental disorder. It is known that intrauterine exposure to valproate can cause undesirable effects on the mental and physical development of children who have succumbed to its influence. This risk is likely to be dose-dependent, but it has not been possible to establish a dose cut-off value below which there is no risk from the available data. The exact period of pregnancy during which there is a risk of these effects has not been determined, and the possibility of risk throughout the entire period of pregnancy cannot be ruled out. It has been reported that studies involving preschool children who were exposed to valproate during intrauterine development showed that developmental delays, such as delayed speech and gait development, decreased intellectual function, insufficient speaking skills (speaking speech and speech comprehension) and memory impairment.

There is evidence that the intelligence quotient (IQ) measured in school-aged children (up to 6 years old) who were exposed to valproate during intrauterine development was, on average, 7-10 points lower than in children who were exposed to other antiepileptic preparations.

Although the role of other factors cannot be ruled out, there is evidence that the risk of intellectual decline in children exposed to valproate may not be related to maternal IQ. There are insufficient data on long-term effects. Existing evidence suggests that children who have been exposed to valproate in utero have an increased risk of autism spectrum disorders (about 3 times) and childhood autism (about 5 times) compared to the general study population.

Limited evidence suggests that children who have been exposed to valproate in utero are more likely to develop symptoms of attention deficit hyperactivity disorder.

Female children, female adolescents and women of reproductive age (see information above and SPECIAL INSTRUCTIONS).

If a woman is planning a pregnancy. If a woman is planning a pregnancy, other treatments should be considered. If possible, every effort should be made to replace the preparation in women planning to become pregnant with an appropriate alternative treatment before conception. Treatment with valproate should not be discontinued without reevaluation by a physician who has experience in treating epilepsy, the benefits and risks of such therapy for the patient. If, based on a careful assessment of the risks and benefits, it is decided to continue treatment with valproate during pregnancy, the following is recommended.

If the use of sodium valproate cannot be avoided (or there is no alternative), it is recommended to take the preparation in the minimum effective daily dose and to give preference to forms of prolonged action, and if this is not possible, then divide the dose into several doses in order to avoid reaching the Cmax of valproic acid in blood plasma.

Taking folate supplements before pregnancy can reduce the risk of fetal neural tube defects that are common in all pregnancies. However, existing data do not support that this prevents birth defects or malformations due to exposure to valproate.

It is necessary to carry out specialized prenatal monitoring in order to identify possible defects in the development of the neural tube in the fetus or other malformations.

During pregnancy, if treatment with valproate is continued, it is recommended to take the preparation in the minimum effective daily dose and, if possible, avoid doses exceeding 1000 mg / day. Coagulation tests should be performed in the mother before childbirth and in the newborn, in particular, to determine the number of platelets, the level of fibrinogen in the blood plasma and the blood clotting time (activated partial thromboplastin time).

Risk in the neonatal period. In newborns whose mothers took valproate during pregnancy, hemorrhagic syndrome may occur. This hemorrhagic syndrome is associated with thrombocytopenia, hypofibrinogenemia, and / or decreased levels of other coagulation factors. Afibrogenaemia has also been reported, which can be fatal. However, it is necessary to distinguish this syndrome from a decrease in vitamin K levels caused by phenobarbital and enzyme inducers. In this regard, in newborns, it is necessary to determine the number of platelets, the level of fibrinogen in the blood plasma, conduct coagulation tests and determine the factors of blood coagulation. Cases of hypoglycemia have been reported in newborns whose mothers took valproate during the third trimester of pregnancy. Cases of hypothyroidism have been reported in newborns whose mothers took valproate during pregnancy.

Withdrawal symptoms may develop in newborns whose mothers took valproate during the last trimester of pregnancy (in particular, in the form of nervous excitement, irritability, increased excitability, increased neuro-reflex excitability, hyperkinesia, tonic disorders, tremors, seizures, and disorders of the sucking reflex) ...

Breastfeeding period. Valproate is excreted in breast milk at a concentration of 1–10% of its maternal plasma level. Blood disorders have been observed in newborns / infants whose mothers received treatment with this preparation (see SIDE EFFECTS).

The decision as to whether to stop breastfeeding or to stop / refrain from taking Valprocom Chrono should be made taking into account the benefits of breastfeeding for the baby and the benefits of the treatment for the woman.

Fertility There have been reports of cases of amenorrhea, polycystic ovary disease, and increased testosterone levels in women taking valproate (see SIDE EFFECTS). The use of valproate can also lead to impaired fertility in men (see SIDE EFFECTS). In the cases reported, it is noted that fertile dysfunction is reversible and disappears after discontinuation of preparation treatment.

The ability to influence the reaction rate when driving or working with other mechanisms. Due to possible undesirable effects, the preparation Valprocom Chrono affects the ability to drive vehicles and work with mechanisms. Patients should be warned of the risk of drowsiness, especially if they are receiving complex anticonvulsant therapy or concomitant therapy with benzodiazepines (see INTERACTIONS).

Interactions

The effect of valproate on other preparations. valproic acid inhibits cytochrome p450 isozymes (cyp 2c9 and cyp 3a). therefore, the metabolic effects that can be expected can be anticipated given the relevant data. simultaneous use with preparations that can cause seizures or lower the seizure threshold should be considered or not recommended or generally contraindicated, depending on the possible risk.

Most antidepressants (imipramines, selective serotonin reuptake inhibitors), MAO inhibitors, benzodiazepines, antipsychotics (phenothiazines and butyrophenones), mefloquine, chloroquine, buproprion, tramadol. In this regard, clinical observation and, possibly, correction of therapy are necessary.

Contraindicated combinations (see CONTRAINDICATIONS):

with mefloquine - the risk of epileptic seizures in patients with epilepsy due to increased metabolism of valproic acid and the convulsant effect of mefloquine;

with St. John's wort preparations - the risk of a decrease in the concentration of valproic acid in the blood plasma and a decrease in the effectiveness of the preparation.

Combinations not recommended

With lamotrigine, sodium valproate slows down the metabolism of lamotrigine and almost doubles the mean T½ of lamotrigine.

This interaction can lead to an increase in the toxic effect of lamotrigine, in particular to the occurrence of severe skin reactions.

Several serious skin reactions have been reported that developed during the first 6 weeks of combination therapy and were partially relieved by discontinuation of such therapy or sometimes only after appropriate treatment.

Therefore, it is recommended to carry out clinical monitoring, as well as, if necessary, dose adjustment (reduce the dose of lamotrigine).

With carbapenem agents (panipenem, meropenem, imipenem) - a decrease in blood valproic acid levels has been reported with simultaneous use with carbapenem agents, as a result of which valproic acid levels decrease by 60-100% within 2 days, which is sometimes accompanied by seizures. Due to the rapid and significant decrease in the concentration of the preparation, the simultaneous use of carbapenem agents in stabilized patients taking valproic acid should be avoided. If treatment with these antibiotics cannot be avoided, then blood sodium valproate levels should be closely monitored.

Combinations requiring special care when using

With aztreonam - the risk of seizures due to a decrease in the concentration of valproic acid in the blood plasma. Clinical observation of the patient's condition, determination of the concentration of preparations in the blood plasma and correction of the dose of the anticonvulsant preparation during treatment with an antibacterial preparation and after its cancellation are necessary.

With phenytoin (and by extrapolation - with phosphenytoin) - the total concentration of phenytoin in the blood plasma changes; there is a risk of a decrease in the concentration of valproic acid in the blood plasma due to the increase in its metabolism in the liver under the action of phenytoin. Clinical observation of the patient's condition, determination of the concentrations of both antiepileptic preparations in blood plasma and, possibly, correction of their dosage are recommended.

With carbamazepine - there is an increase in the concentration of the active metabolite of carbamazepine in the blood plasma, the appearance of symptoms of its overdose. In addition, a decrease in the concentration of valproic acid in blood plasma due to an increase in its metabolism in the liver under the action of carbamazepine. With the combined use of the preparation Valprocom Chrono with carbamazepine, clinical observation of the patient's condition, determination of the concentration of both preparations in the blood plasma and correction of their dosage are recommended.

With phenobarbital, primidone - preparations accelerate the elimination of the preparation Valprocom Chrono from the body and thus reduce its effectiveness. In addition, there is an increase in the concentration of phenobarbital or primidone in the blood plasma with the appearance of signs of overdose (sedation), usually in children. Clinical observation of the patient's condition during the first 15 days of combination treatment and an immediate reduction in the dose of phenobarbital or primidone with the onset of symptoms of sedation, as well as determination of the levels of both antiepileptic preparations in the blood are recommended.

With topiramate or acetazolamide - the risk of hyperammonemia or encephalopathy caused by valproic acid, taken in combination with topiramate or acetazolamide. Enhanced clinical and laboratory monitoring is recommended at the beginning of treatment and in the event of any symptoms indicating the occurrence of these phenomena.

With felbamate - the rate of excretion of valproic acid decreases by 22-50%, and therefore there is an increase in the concentration of valproic acid in the blood plasma and the risk of overdose. Valproic acid can reduce the average excretion rate of felbamate by up to 16%. Clinical observation of the patient's condition, determination of the concentration of felbamate in the blood plasma and, possibly, correction of the dosage of the preparation Valprocom Chrono during treatment with felbamate and after its cancellation are recommended.

With rifampicin - it can reduce the level of valproate in the blood, which leads to a decrease in its therapeutic effect. When valproate is used concomitantly with rifampicin, a dose adjustment of valproate may be necessary.

With zidovudine - the use of sodium valproate / valproic acid can lead to a pronounced increase in the plasma concentration of zidovudine, while the risk of toxic effects of zidovudine increases.

With rufinamide - valproic acid can provoke an increase in plasma concentrations of rufinamide. This increase depends on the concentrations of valproic acid. Care must be taken, especially in the case of use in children, since this effect is more pronounced in this patient population.

With quetiapine - Concomitant use of valproate and quetiapine may increase the risk of neutropenia / leukopenia.

Concomitant use with protease inhibitors such as lopinavir and ritonavir increases plasma concentrations of valproate.

Concomitant use with cholestyramine can lead to a decrease in plasma concentrations of valproate.

Combinations to be taken into account

With nimodipine (orally and by extrapolation - parenteral) - an increase in the hypotensive effect of nimodipine due to an increase in its concentration in blood plasma (weakening of metabolism by valproic acid).

Other types of interactions

With cimetidine, erythromycin, isoniazid - an increase in plasma levels of valproate as a result of a slowdown in hepatic metabolism when used simultaneously with cimetidine, erythromycin and isoniazid.

The simultaneous use of the preparation Valprocom Chrono and salicylates should be avoided, given that these preparations are metabolized in the same way, while valproic acid is displaced from the connection with proteins and its effect may be enhanced.

With lithium - sodium valproate does not affect plasma lithium levels.

With oral contraceptives - valproate does not induce enzyme induction, therefore it does not reduce the effectiveness of estrogen-progestogens in women using hormonal contraceptives. For the same reason, it does not reduce the total plasma concentration of vitamin K antagonists.However, against the background of the use of Valprokom Chrono with anticoagulants and acetylsalicylic acid, it can lead to an increase in the tendency to bleeding. For example, when using the preparation Valprocom Chrono, an increase in the free fraction of warfarin may be noted, since warfarin is competitively displaced from its binding sites with albumin. Therefore, prothrombin levels should be closely monitored during treatment with vitamin K antagonists.

The simultaneous use of valproate with olanzapine may increase the risk of neutropenia, tremor, dry mouth, increased appetite, weight gain, speech impairment and drowsiness.

Potentially hepatotoxic preparations and alcohol can increase the hepatotoxicity of valproic acid.

It is recommended to use sodium valproate with caution in combination with new antiepileptic preparations, whose pharmacodynamic and pharmacokinetic properties may not be well defined.

Overdose

Symptoms at plasma concentrations 5–6 times higher than the therapeutic maximum, nausea, vomiting and dizziness may occur.

With a significant overdose, a coma, superficial or deep, accompanied by muscle hypotension, hyporeflexia, miosis, respiratory depression and metabolic acidosis may occur, intracranial hypertension associated with cerebral edema, circulatory collapse / shock is possible.

However, symptoms can vary and seizures can occur if plasma levels are very high.

The presence of sodium in valproate can lead to hyponatremia in overdose.

Treatment. There is no specific antidote. Symptomatic treatment: gastric lavage, if no more than 10-12 hours have passed after taking the preparation, ensuring osmotic diuresis, monitoring and correcting the functional state of the cardiovascular and respiratory systems.

Naloxone has been used successfully in a few isolated cases. If necessary, hemodialysis and hemoperfusion are performed.

The prognosis for overdose is usually good. However, several cases of fatal overdose of valproate have been described.

Storage conditions

In original packaging at a temperature not exceeding 25 ° c. do not refrigerate or freeze!

Tags: Valprocom

Reviews Valprocom 300 Chrono 100 tablets — Made in Ukraine — Free Delivery

There are no reviews for this product.

Write a review

Buyers Online