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.
Convulex®
There is evidence of the possible occurrence of suicidal thoughts and behavior in patients receiving antiepileptic drugs. A meta-analysis of clinical trials of antiepileptic drugs found a slightly increased risk of suicidal ideation and behavior. The mechanism of this phenomenon is not fully understood; the possibility of an increased risk of suicidal thoughts and behavior when using valproic acid drugs cannot be ruled out. Patients, their families, and health care providers caring for such patients should be informed of the risk of suicidal thoughts and behavior.
Due to reports of severe and fatal cases of liver failure and pancreatitis when using valproic acid preparations, the following should be kept in mind:
— a high-risk group includes infants and children under 3 years of age with severe epilepsy, often associated with brain damage and congenital metabolic 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 hysterical 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 - the activity of “liver” transaminases, the content of prothrombin, fibrinogen, blood clotting factors, bilirubin concentration, as well as amylase activity (every 3 months, especially when combined with other antiepileptic drugs). means) and the picture of peripheral blood, in particular blood platelets. The development of severe thrombocytopenia (below 75 x 109/l) has been described during treatment with high doses of valproic acid (with plasma levels above 110 mg/l in women and 135 mg/l in men). The platelet count returned to normal when treatment was stopped, and in some patients it returned to normal without treatment being stopped.
Hypothermia may occur during treatment with valproic acid, both with and without hyperammonemia. Hypothermia may be accompanied by lethargy, confusion, coma, and disturbances in cardiovascular activity and breathing.
When using valproic acid, even with normal liver function tests, hyperammonemia may occur. The level of ammonium in the blood should be determined if patients experience drowsiness, vomiting, changes in mental status, or hypothermia. If severe hyperammonemia is detected, treatment with valproic acid should be discontinued. Hyperammonemic encephalopathy (in some cases, fatal) when using valproic acid can develop in patients with disorders of urea metabolism, in particular with ornithine transcarbamylase deficiency. Before starting treatment with valproic acid, the state of urea metabolism should be examined in patients with a history of encephalopathy or coma of unknown origin, with periodic vomiting and lethargy, episodes of irritability, ataxia, and a family history of disorders of urea metabolism. Patients with hyperammonemic encephalopathy that develops during therapy with valproic acid should urgently receive appropriate treatment, including discontinuation of valproic acid.
In patients receiving other antiepileptic drugs, the transition 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.
When using the drug 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 the drug.
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.
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.
Convulex tablets 300 mg 50 pcs. in Vidnoye
Valproic acid enhances the effects, including side effects, of other antiepileptic drugs (phenytoin lamotrigine), antidepressants, antipsychotic drugs (neuroleptics), anxiolytics, barbiturates, monoamine oxidase inhibitors (MAOIs), thymoleptics, ethanol.
The addition of valproic acid to clonazepam in isolated cases can lead to increased severity of absence status.
With simultaneous use of valproic acid with barbiturates or primidone, an increase in the concentration of the latter in the blood plasma is observed.
Increases the T1/2 of lamotrigine (inhibits liver enzymes and causes a slowdown in the metabolism of lamotrigine, as a result of which its T1/2 is extended to 70 hours in adults and to 45-55 hours in children).
Reduces the clearance of zidovudine by 38% while its T1/2 does not change.
Tricyclic antidepressants, MAO inhibitors, antipsychotics (neuroleptics) and other drugs that lower the threshold for seizure activity reduce the effectiveness of the drug.
When taking the drug Convulex® simultaneously with ethanol and other drugs that depress the central nervous system (tricyclic antidepressants, MAO inhibitors, antipsychotic drugs), increased depression of the central nervous system is possible.
When combined with salicylates, an increase in the effects of valproic acid is observed (displacement from plasma proteins).
Konvulex® enhances the effect of antiplatelet agents (acetylsalicylic acid) and indirect anticoagulants.
When combined with phenobarbital, phenytoin, carbamazepine, and mefloquine, the content of valproic acid in the blood serum decreases (acceleration of metabolism).
Felbamate increases the concentration of valproic acid in plasma by 35-50% (dose adjustment is necessary).
Myelotoxic drugs - increased risk of inhibition of bone marrow hematopoiesis.
Valproic acid does not induce liver enzymes and does not reduce the effectiveness of oral contraceptives.
Ethanol and hepatotoxic drugs increase the likelihood of developing liver damage.
Valproic acid can either increase or decrease the serum concentration of ethosuximide due to changes in metabolism.
Meropenem reduces the plasma concentration of valproic acid, which may lead to a decrease in the anticonvulsant effect.
When used simultaneously with topiramate, the risk of developing hyperammonemia and encephalopathy increases.
