Convulex

Contraindicated combinations

Mefloquine: risk of epileptic seizures due to increased metabolism of valproic acid and a decrease in its plasma concentration and, on the other hand, the convulsant effect of mefloquine.

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

Not recommended combinations

Lamotrigine: increased risk of severe skin reactions (toxic epidermal necrolysis). Valproic acid inhibits microsomal liver enzymes that ensure the metabolism of lamotrigine, which slows down its T1/2 to 70 hours in adults and up to 45-55 hours in children and increases plasma concentrations. If the combination is necessary, careful clinical and laboratory monitoring is required.

Combinations requiring special precautions

Carbamazepine: Valproic acid increases the plasma concentration of the active metabolite of carbamazepine to the point of signs of overdose. In addition, carbamazepine enhances the hepatic metabolism of valproic acid and reduces its concentration. These circumstances require the attention of a doctor and determination of drug concentrations in plasma and a possible revision of their doses.

Phenobarbital, primidone: Valproic acid increases plasma concentrations of phenobarbital or primidone to the point of signs of overdose, more often in children. In turn, phenobarbital or primidone enhance the hepatic metabolism of valproic acid and reduce its concentration. Clinical observation is recommended during the first 2 weeks of combination treatment with an immediate reduction in the dose of phenobarbital or primidone if signs of sedation appear, and determination of the level of anticonvulsants in the blood.

Phenytoin: changes in the concentration of phenytoin in plasma are possible; phenytoin increases the hepatic metabolism of valproic acid and reduces its concentration. Clinical observation is recommended, determining the level of anticonvulsants in the blood, changing dosages if necessary.

Clonazepam: The addition of valproic acid to clonazepam in isolated cases may lead to an increase in the severity of absence status.

Ethosuximide: Valproic acid can either increase or decrease the serum concentrations of ethosuximide due to changes in its metabolism. Clinical observation is recommended, determining the level of anticonvulsants in the blood, changing dosages if necessary.

Topiramate: Increases the risk of hyperammonemia and encephalopathy.

Felbamate: increased plasma concentrations of valproic acid by 35-50%, with risk of overdose. Clinical observation, determination of the level of valproic acid in the blood, and changes in the dosage of valproic acid when combined with felbamate and after its discontinuation are recommended.

Neuroleptics, MAO inhibitors, antidepressants, benzodiazepines: neuroleptics, tricyclic antidepressants, MAO inhibitors, which lower the seizure threshold, reduce the effectiveness of the drug. In turn, valproic acid potentiates the effect of these psychotropic drugs, as well as benzodiazepines.

Cimetidine, erythromycin: suppress the hepatic metabolism of valproic acid and increase its plasma concentration.

Zidovudine: Valproic acid increases the plasma concentration of zidovudine, leading to increased toxicity.

Carbapenems, monobactams: meropenem, panipenem, as well as aztreonam and imipenem reduce the concentration of valproic acid in plasma, which may lead to a decrease in the anticonvulsant effect.

Combinations to consider

Acetylsalicylic acid: increased effects of valproic acid due to its displacement from plasma proteins. Valproic acid enhances the effect of acetylsalicylic acid.

Indirect anticoagulants: valproic acid enhances the effect of indirect anticoagulants; careful monitoring of the prothrombin index is necessary when administered together with vitamin K-dependent anticoagulants.

Nimodipine: increased hypotensive effect of nimodipine due to an increase in its concentration in plasma due to the suppression of its metabolism by valproic acid.

Myelotoxic drugs: increased risk of suppression of bone marrow hematopoiesis.

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

Other combinations

Oral contraceptives: valproic acid does not induce liver microsomal enzymes and does not reduce the effectiveness of hormonal oral contraceptives.

Konvulex, 300 mg, extended-release film-coated tablets, 50 pcs.

Due to reports of severe and fatal cases of liver failure and pancreatitis with the use of valproic acid drugs, the following should be kept in mind: - infants and children under 3 years of age are at increased risk, with severe epilepsy, often associated with brain damage and congenital metabolic disorders. or degenerative diseases; - in most cases, liver dysfunction developed in the first 6 months (usually between 2 and 12 weeks) of treatment, more often with combined antiepileptic treatment; - cases of pancreatitis were observed regardless of the patient’s age and duration of treatment, although the risk of developing pancreatitis decreased with the patient’s age; — insufficiency of liver function in pancreatitis increases the risk of death; - early diagnosis (before the icteric stage) is based mainly on clinical observation - identification of early symptoms such as asthenia, anorexia, extreme fatigue, drowsiness, sometimes accompanied by vomiting and abdominal pain; in this case, a relapse of epileptic seizures may occur against the background of unchanged antiepileptic therapy. In such cases, you should immediately consult a doctor for a clinical examination and liver function test. During treatment, especially in the first 6 months, it is necessary to periodically check liver function - liver transaminase activity, levels of prothrombin, fibrinogen, coagulation factors, bilirubin concentration, as well as amylase activity (every 3 months, especially when combined with other antiepileptic drugs) and picture of peripheral blood, in particular blood platelets. In 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 not treated 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, a general blood test (including platelet count), determination of bleeding time, and coagulogram parameters are required. If symptoms of an “acute” abdomen occur during treatment, before surgery, it is recommended to determine the activity of amylase in the blood to exclude acute pancreatitis. During treatment, one should take into account the possible distortion of the results of urine tests in diabetes mellitus (due to an increase in the content of ketone bodies) and 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 agents. Abruptly stopping taking Convulex may lead to an increase in epileptic seizures. Impact on the ability to drive vehicles and operate machinery During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Konvulex syrup for epilepsy, 50 mg/ml, 100 ml

Female children/female adolescents/women of reproductive age/pregnant women. Due to the high teratogenic potential and risk of developmental disorders in neonates exposed in utero to valproate, Convulex should not be used in female children, adolescent females, women of reproductive potential, and pregnant women unless alternative treatments are ineffective or ineffective. tolerated by patients. The benefits and risks of this drug should be carefully reviewed during regular treatment evaluations, during puberty, and promptly when a woman of reproductive age who is taking Convulex plans to become pregnant or becomes pregnant.

Women of reproductive age should use effective contraception during treatment with the drug and should be advised of the risks associated with the use of Convulex during pregnancy (see section "Use during pregnancy or lactation").

The prescriber should ensure that the patient is provided with comprehensive risk information in the form of appropriate materials, such as a patient information leaflet, to help her better understand the risks of using the drug.

In particular, the doctor prescribing the drug must make sure that the patient understands:

the nature and importance of the risks associated with the influence of the drug during pregnancy, in particular teratogenic risks and risks of developmental disorders;
the need to use effective contraception;
the need for regular assessment of treatment;
the need to immediately consult a doctor if you are planning or are likely to become pregnant.

If possible, all measures should be taken to replace the drug in women planning pregnancy with an appropriate alternative treatment method before fertilization (see Section “Use during pregnancy or lactation”).

Treatment with valproate should only be continued after a physician experienced in the treatment of epilepsy has reassessed the benefits and risks of such therapy for the patient.

The initiation of an antiepileptic drug may be accompanied by a resumption of epileptic seizures or the occurrence of severe seizures or the development of new types of seizures in the patient, regardless of the spontaneous fluctuations observed in some epileptic conditions. In the case of the use of valproate, this primarily concerns changes in the combination therapy regimen with antiepileptic drugs or pharmacokinetic interactions (see Section "Interaction with other drugs and other types of interactions"), toxicity (liver disease or encephalopathy - see Section "Adverse reactions" ) or overdose. The drug should only be administered intravenously. Intramuscular injections of this drug cannot be given because there is a risk of developing local tissue necrosis.

Liver dysfunction. There are isolated reports of severe and sometimes fatal cases of liver damage.

At increased risk are infants and children under 3 years of age with severe epilepsy, especially epilepsy associated with brain damage, mental retardation, and/or congenital metabolic or degenerative disease of the nervous system. From the age of 3 years, the frequency of such complications decreases significantly and gradually decreases with age.

In the vast majority of cases, such liver damage was observed during the first 6 months of treatment, usually within 2-12 weeks, and most often with complex antiepileptic therapy.

Early diagnosis is based primarily on clinical symptoms. First of all, you should take into account two types of symptoms that may precede the onset of jaundice, especially in patients at risk:

general nonspecific symptoms, such as general weakness, lack of appetite, fatigue, drowsiness, which usually occur suddenly and are sometimes accompanied by repeated vomiting and abdominal pain;
recurrence of epileptic seizures despite proper adherence to treatment.

It is recommended to inform the patient (and if it is a child, then his parents) that if such clinical symptoms appear, you should immediately consult a doctor. In addition to clinical examination, liver function tests should be performed immediately.

Liver function should be checked periodically during the first 6 months of treatment. Among traditional tests, the most important are tests that reflect the protein-synthetic function of the liver, especially prothrombin time. If a too low PT value is detected, especially if this is accompanied by changes in other laboratory parameters (a significant decrease in the level of fibrinogen and coagulation factors, an increase in the level of bilirubin and transaminase activity - see Section “Peculiarities of Application”), treatment with valproate should be discontinued. Salicylate derivatives should be discontinued if these drugs are administered concomitantly as they share the same metabolic pathways.

Pancreatitis. Cases of pancreatitis have been observed extremely rarely, sometimes ending in death. These cases did not depend on the patient's age or duration of treatment. Young children are a particular risk group. Pancreatitis, which is accompanied by negative consequences, is most often observed 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. If acute abdominal pain or gastrointestinal symptoms such as nausea, vomiting and/or lack of appetite occur, a diagnosis of pancreatitis (including blood amylase measurements) should be considered. Patients with elevated pancreatic enzyme levels should discontinue therapy and take appropriate alternative therapeutic measures.

Women of reproductive age. This drug should not be used by women of reproductive age unless absolutely necessary, such as when other medications are ineffective or intolerant. This should be clarified before prescribing Convulex for the first time or if a woman of reproductive age who is receiving Convulex therapy plans to become pregnant. During treatment, women of reproductive age should use effective methods of contraception.

Risk of suicide. There have been reports of suicidal thoughts and behavior in patients receiving antiepileptic drugs for some indications. A meta-analysis of data from randomized placebo-controlled trials of antiepileptic drugs also showed a small increase in the risk of suicidal ideation and behavior. The reasons for this increased risk are not clear, and the available data do not provide grounds to exclude an increase in this risk during treatment with valproate. In this regard, it is necessary to carefully monitor the patient's condition in order to identify any signs of suicidal thoughts and behavior, as well as prescribe appropriate treatment. Patients (and their caregivers) should be advised to seek medical attention if suicidal thoughts or behavior occur.

Interaction with other drugs. The simultaneous use of this drug with lamotrigine and penemama is not recommended (see Section “Interaction with other drugs and other types of interactions”).

The drug should not be used with salicylates in children under 16 years of age (see Aspirin/Salicylates Reference for Reye's Syndrome).

Precautions for use. Laboratory testing of liver function should be carried out before starting treatment (see section "Contraindications") and periodically during the first 6 months of treatment, especially in patients at risk (see section "Peculiarities of use").

When treated with this drug, especially at the beginning, as with treatment with other antiepileptic drugs, an isolated and temporary moderate increase in transaminase levels without any clinical manifestations may be observed. In this case, it is recommended to conduct a full laboratory examination (in particular, determine the prothrombin time) and, possibly, review the dosage of the drug and conduct repeated tests depending on changes in indicators.

Before starting therapy, before any surgical intervention, as well as in the event of hematomas or spontaneous bleeding, it is recommended to perform blood tests (complete blood count, including platelet count, assessment of bleeding time and blood coagulation parameters) (see “Adverse reactions” ").

For patients with renal failure, the possibility of increasing the concentration of the free form of valproic acid in the blood plasma should be taken into account and the dose of the drug should be reduced accordingly. Since it is sometimes very difficult to interpret data on the concentration of the drug in the blood plasma, the dose must be adjusted depending on the clinical effect obtained.

This drug is not recommended for use in patients with urea cycle enzyme deficiency. In such patients, cases of hyperammonemia, which were accompanied by stupor or coma, have been described.

Although immune dysfunction has been observed extremely rarely during treatment with valproate, the potential benefits of valproate should be carefully weighed against the potential risks when prescribing the drug to patients with systemic lupus erythematosus.

Before starting treatment, patients should be warned about the risk of weight gain, and appropriate measures, mainly of a dietary nature, should be taken to minimize this phenomenon.

Patients with concomitant carnitine palmitoyltransferase (CPT) type II deficiency should be warned of the increased risk of rhabdomyolysis when taking valproate.

Effect on laboratory and diagnostic tests. Because valproate is excreted primarily by the kidneys, partly in the form of ketone bodies, urine ketone body testing may give a false positive result in patients with diabetes mellitus.

During therapy with Convulex, it is recommended to avoid drinking alcohol.