Composition, form of production and packaging
The solution for intravenous administration is clear, colorless or almost colorless.
1 ml of 1 amp.
valproic acid 86.78 mg 433.9 mg,
which corresponds to the content of sodium valproate 100 mg 500 mg
Excipients: sodium hydroxide - 117 mg, disodium hydrophosphate dodecahydrate - 71.8 mg, water d / and - up to 5 ml.
5 ml - ampoules of colorless glass (5) - plastic pallets (1) - cardboard packs.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
Antiepileptic drug. It also has a central muscle relaxant and sedative effect.
The mechanism of action is due to inhibition of the enzyme GABA-transferase and an increase in GABA in the CNS. GABA interferes with pre- and postsynaptic discharges and thereby prevents the spread of convulsive activity in the central nervous system. In addition, the action of valproic acid on the GABA A receptors plays an important role in the mechanism of action of the drug, as well as the effect on voltage-dependent Na channels. According to another hypothesis, valproic acid acts on the sites of postsynaptic receptors, imitating or enhancing the inhibitory effect of GABA. A possible direct effect on membrane activity is associated with changes in potassium conductivity.
It improves the mental state and mood of patients, has antiarrhythmic activity.
C ss with iv introduction is achieved within a few minutes and can be maintained by a slow infusion. The therapeutic concentration of the drug in the blood plasma varies between 50-150 mg / l.
Valproic acid is associated with plasma proteins by 90-95% at a plasma concentration of up to 50 mg / l and by 80-85% at a concentration of 50-100 mg / l, with uremia, hypoproteinemia and cirrhosis, the binding to proteins is reduced.
Levels of concentration in the cerebrospinal fluid correlate with the value of the protein-free fraction of the drug, amounting to about 10% of the serum level. Valproic acid penetrates the placental barrier, excreted in breast milk. Concentration in breast milk is 1-10% concentration in the blood plasma of the mother.
Metabolism and excretion
The drug is subjected to glucuronidation and oxidation in the liver.
Metabolites and unaltered valproic acid (1-3% of the dose) are excreted by the kidneys, small amounts are excreted with feces and with exhaled air. T 1/2 of thepreparation is in healthy subjects and with monotherapy of 8 to 20 hours, when combined with other drugs, T 1/2 can be 6-8 hours due to the induction of metabolic enzymes, in patients with impaired liver function and elderly patients T 1 / 2 can be much longer.
Treatment of epileptic seizures:
- generalized: absences, myoclonic seizures, tonic-clonic, atonic, mixed;
- partial: simple, complex, secondarily generalized seizures;
- Specific syndromes (Vesta, Lennox-Gastaut).
Febrile convulsions in children.
Treatment and prevention of bipolar affective disorders.
The drug is administered intravenously (slowly) or infusion.
The recommended daily dose for intravenous administration is 5-10 mg of sodium valproate / kg body weight.
With IV infusion introduction, the recommended dose is 0.5-1 mg of sodium valproate / kg body weight / h.
When switching from oral to intravenous administration, the dose does not change, the first IV administration is recommended 12 hours after the last oral ingestion.The injection for injections should be replaced by taking the drug inside as soon as the patient's condition allows. The first intake is also recommended 12 hours after the last injection.
If you need to quickly achieve and maintain a high concentration in the plasma, the following dosing regimen is recommended: intravenous administration at a dose of 15 mg / kg for 5 minutes, after 30 minutes, start infusion at a rate of 1 mg / kg / h with constant concentration monitoring to a level in plasma of about 75 Ојg / ml.
The maximum daily dose of the drug should not exceed 2500 mg.
The average daily doses are 20 mg / kg in adults (including elderly patients) , 25 mg / kg in adolescents , and 30 mg / kg in children .
As an infusion solution for Convulex, isotonic sodium chloride solution, 5% glucose solution, Ringer's solution can be used. The prepared infusion solution can be used for 24 hours, the unused volume of the solution is destroyed. If IV drugs are used, Convoulex В® should be administered by a separate infusion system.
In general, Convulex В® is well tolerated by patients. Side effects are possible mainly at the level of valproic acid in blood plasma above 100 mg / l or with combined therapy.
On the part of the digestive system: nausea, vomiting, gastralgia, anorexia or increased appetite, diarrhea, hepatitis; rarely - constipation, pancreatitis, up to severe lesions with a lethal outcome (in the first 6 months of treatment, more often for 2-12 weeks).
From the side of the central nervous system: tremor, diplopia, nystagmus, flashing of "flies" before the eyes; rarely changes in behavior, mood or mental state (depression, fatigue, hallucinations, aggressiveness, hyperactive state, psychoses, unusual arousal, motor anxiety or irritability), ataxia, dizziness, drowsiness, headache, dysarthria, stupor, impaired consciousness, coma .
On the part of the hematopoiesis system: anemia, leukopenia, thrombocytopenia, reduction of fibrinogen, platelet aggregation and clotting, accompanied by prolonged bleeding time, petechial hemorrhages, bruising, bruising, bleeding.
From the side of metabolism: decrease or increase in body weight.
On the part of the endocrine system: dysmenorrhea, secondary amenorrhea, breast enlargement, galactorrhea.
On the part of laboratory indicators: hypercreatininaemia, hyperammonemia, hyperbilirubinemia, a slight increase in the activity of hepatic transaminases, LDH (dose-dependent).
Allergic reactions: skin rash, hives, angioedema, photosensitivity, Stevens-Johnson syndrome.
Other: swelling, hair loss (usually recovers after drug discontinuation).
- liver failure;
acute and chronic hepatitis;
- impaired pancreatic function;
- hemorrhagic diathesis;
- severe thrombocytopenia;
- a combination with mefloquine, St. John's wort, perforated, lamotrigine;
- Disorders of urea metabolism (including in family history);
- lactation period;
- Hypersensitivity to valproic acid and its salts or components of the drug.
- in children treated with several antiepileptic drugs;
- in children and adolescents with multiple concomitant diseases and with severe forms of seizures;
- with violations of kidney function;
- in patients with anamnestic data on liver and pancreas diseases;
- with oppression of bone marrow hematopoiesis: leukopenia, anemia, thrombocytopenia;
- with congenital enzymopathy;
- with organic brain lesions;
- with hypoproteinemia;
- in children under 3 years of age;
- during pregnancy, especially in the first trimester.
PREGNANCY AND LACTATION
During treatment with the preparation, Convulex В® should be protected from pregnancy.
In the first trimester of pregnancy, do not start treatment with Conlevix. If the pregnant woman is already receiving the drug, then due to the risk of more seizures, treatment should not be interrupted. The drug should be used at the lowest effective dose, avoiding the combination with other anticonvulsants and, if possible, regularly monitoring the level of the drug in the plasma.
In experimental studies on animals, the teratogenic effect of valproic acid has been revealed.
The incidence of neural tube defects in children born to women taking valproate in the first trimester of pregnancy is 1-2%. It is advisable in this regard, the use of folic acid preparations.
During the lactation period, the use of Convoulex В® is contraindicated. At the same time, breastfeeding is possible, because the concentration in breast milk does not exceed 1-10% of the level of the drug in the blood plasma of the mother.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution: for violations of kidney function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindications: marked violations of the liver.
APPLICATION FOR CHILDREN
With caution: in children in the treatment of several antiepileptic drugs; in children and adolescents with multiple concomitant diseases and with severe forms of seizures.
APPLICATION IN ELDERLY PATIENTS
The average daily doses are 20 mg / kg in adults (including elderly patients).
In connection with the available reports of severe and lethal cases of hepatic insufficiency and pancreatitis with the use of valproic acid preparations, it is necessary to bear in mind the following:
- At-risk groups are 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 function abnormalities 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 age of the patient;
- Lack of liver function in pancreatitis increases the risk of death;
- early diagnosis (before the icteric stage) is based mainly on clinical observation - the detection of early symptoms such as asthenia, anorexia, extreme fatigue, drowsiness, sometimes accompanied by vomiting and abdominal pain; with the recurrence of epileptic seizures against a background of unchanged antiepileptic therapy.
In such cases, you should immediately consult a doctor for clinical examination and liver function analysis.
During treatment, especially in the first 6 months, it is necessary to periodically check the liver function - the activity of hepatic transaminases, the level of prothrombin, fibrinogen, coagulation factors, bilirubin concentration, and amylase activity (every 3 months, especially when combined with other antiepileptic drugs) and the picture peripheral blood, in particular, blood platelets.
Patients who receive other antiepileptic drugs, transfer to treatment with valproic acid should be carried out gradually, reaching a clinically effective dose after 2 weeks, after which a gradual cancellation of other antiepileptic drugs is possible. In patients who have not been treated with other antiepileptic drugs, a clinically effective dose should be achieved after 1 week.
The risk of developing side effects from the liver is increased when combined anticonvulsant therapy, as well as in children.
Do not drink drinks containing ethanol.
Before the surgical intervention, a general blood test (including platelet numbers), bleeding time, coagulogram indices is required.
If there is a "acute abdomen" symptom complex before treatment, it is recommended to determine the activity of amylase in the blood to exclude acute pancreatitis.
During treatment it is necessary to take into account the possible distortion of the results of urinalysis in diabetes mellitus (due to an increase in the content of ketone bodies), thyroid function indices. With the development of any acute serious side effects, it is necessary to immediately discuss with the doctor the advisability of continuing or discontinuing treatment.
To reduce the risk of dyspeptic disorders, it is possible to take antispasmodics and enveloping agents.
A sharp discontinuation of the preparation of Convulex В® may lead to an increase in epileptic seizures.
Impact on the ability to drive vehicles and manage mechanisms
Patients taking Convullex В® should refrain from engaging in potentially dangerous activities requiring increased attention and speed of psychomotor reactions.
During the period of treatment, patients should be careful when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Symptoms: nausea, vomiting, dizziness, diarrhea, impaired breathing function, muscle hypotension, hyporeflexia, miosis, coma.
Treatment: gastric lavage (not later than 10-12 hours) followed by the appointment of activated charcoal, hemodialysis. Forced diuresis, maintenance of respiratory function and cardiovascular system.
Mefloquine: the risk of epileptic seizures due to increased metabolism of valproic acid and a decrease in its plasma concentration and, on the other hand, an anticonvulsant effect of mefloquine.
St. John's wort: the risk of a decrease in the concentration of valproic acid in the blood plasma.
Not recommended combinations
Lamotrigine: an increased risk of severe skin reactions (toxic epidermal necrolysis). Valproic acid inhibits microsomal liver enzymes that provide lamotrigine metabolism, which slows down its T 1/2 to 70 h in adults and up to 45-55 h in children and increases the concentration in the blood plasma. If this combination is necessary, careful clinical and laboratory testing is required.
Combinations that require special precautions
Carbamazepine: valproic acid increases the concentration of the active metabolite of carbamazepine in plasma to signs of overdose. In addition, carbamazepine increases the hepatic metabolism of valproic acid and reduces its concentration. These circumstances require the attention of the doctor and the determination of the concentration of drugs in the plasma and the possible revision of their doses.
Phenobarbital, primidone: valproic acid increases the concentration of phenobarbital or primidone in plasma to signs of overdose, more often in children. In turn, phenobarbital or primidone increases the hepatic metabolism of valproic acid and reduces its concentration. Clinical observation is recommended during the first 2 weeks of combined treatment with an immediate reduction in the dose of phenobarbital or primidone when signs of a sedative effect appear, and the concentrations of antiepileptic agents in the blood are determined.
Phenytoin: changes in the concentration of phenytoin in the plasma are possible, phenytoin increases the hepatic metabolism of valproic acid and reduces its concentration. Clinical observation, determination of concentrations of antiepileptic agents in the blood, change of doses as needed is recommended.
Clonazepam: the addition of valproic acid to clonazepam in a few cases can lead to an increase in the expression of the absent status.
Ethosuximide: valproic acid can both increase and decrease the concentration of ethosuximide in the blood serum due to a change in its metabolism. Clinical observation is recommended, the concentration of antiepileptic drugs in the blood is determined, and the doses are changed if necessary.
Topiramate: the risk of developing hyperammonemia and encephalopathy increases.
Felbamate: an increase in the concentration of valproic acid in the plasma by 35-50%, the risk of overdose. Clinical observation, valproate acid concentration in the blood, changing the dose of valproic acid when combined with felbamate and after its cancellation is recommended.
Neuroleptics, MAO inhibitors, antidepressants, benzodiazepines: neuroleptics, tricyclic antidepressants, MAO inhibitors that reduce the threshold of convulsive readiness, 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 concentration in the plasma.
Zidovudine: valproic acid increases the concentration of zidovudine in the plasma, which leads to an increase in its toxicity.
Carbapenems, monobactams: meropenem, panipenem, and also to the azemes and imipenem reduce the concentration of valproic acid in the plasma, which can lead to a decrease in the anticonvulsant effect.
Combinations that should be taken into account
Acetylsalicylic acid: an increase in the effects of valproic acid due to its displacement from the bond with 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 required when co-administered with vitamin K-dependent anticoagulants.
Nimodipine: an increase in the hypotensive effect of nimodipine due to an increase in its concentration in the plasma due to the suppression of its metabolism with valproic acid.
Myelotoxic drugs: increased risk of oppression of bone marrow hematopoiesis.
Ethanol and hepatotoxic drugs: increase the likelihood of developing liver damage.
Oral contraceptives: valproic acid does not induce the induction of microsomal liver enzymes and does not reduce the effectiveness of hormonal oral contraceptives.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children, protected from light at a temperature of no higher than 25 В° C. Shelf life - 5 years.