Description
Release form
Drops for oral administration in the form of a clear, colorless or slightly yellowish solution.
Packaging
100 ml – dark glass bottles with a metering device (1) – packs of cardboard.
Pharmacological action
Antiepileptic drug. It also has a central muscle relaxant and sedative effect.
The mechanism of action is mainly due to an increase in the GABA content in the central nervous system due to inhibition of the GABA transferase enzyme. GABA reduces the excitability and convulsive readiness of the motor zones of the brain. In addition, the action of valproic acid on GABAA receptors (activation of GABA-ergic transmission), as well as the effect on voltage-dependent sodium channels, play a significant role in the drug s mechanism of action.
According to another hypothesis, it acts on sites of postsynaptic receptors, mimicking or enhancing the inhibitory effect of GABA. A possible direct effect on membrane activity is associated with changes in conductivity for potassium ions. Improves the mental state and mood of patients, has antiarrhythmic activity.
Pharmacokinetics
Absorption
Valproic acid is almost completely absorbed from the digestive tract, oral bioavailability is 100%. Eating does not reduce the rate of absorption. Cmax in plasma is observed after 2-3 hours. The therapeutic concentration of valproic acid in plasma is 50-150 mg / L.
Distribution of
Css is achieved on days 2-4 of treatment, depending on the interval between doses.
At a plasma concentration of up to 50 mg / L, the binding of valproic acid to plasma proteins is 90-95%, at a concentration of 50-100 mg / L – 80-85%.
Concentrations in cerebrospinal fluid correlate with the amount of the non-protein fraction of the active substance. Valproic acid crosses the placental barrier, excreted in breast milk. The concentration in breast milk is 1-10% of the concentration in the blood plasma of the mother.
Metabolism
Valproic acid undergoes glucuronidation and oxidation in the liver.
Excretion
Valproic acid (1-3% of the dose) and its metabolites are excreted by the kidneys, small amounts – with feces and expired air. T1 / 2 in monotherapy and in healthy volunteers is 8-20 hours.
Pharmacokinetics in special clinical cases
With uremia, hypoproteinemia and cirrhosis, the binding of valproic acid to plasma proteins decreases.
When combined with other drugs, T1 / 2 may be 6 8 hours due to the induction of metabolic enzymes.
In patients with impaired liver function, elderly patients and children under the age of 18 months, a significant increase in T1 / 2 is possible.
Indications
epilepsy of various etiologies (idiopathic, cryptogenic and symptomatic)
generalized epileptic seizures in adults and children (clonic, tonic, tonic-clonic, absences, myoclonic, atonic)
partial epileptic seizures in adults and children (with or without secondary generalization)
specific syndromes (Vesta, Lennox-Gastaut)
behavioral disorders due to epilepsy
febrile seizures in children, childhood tics and prevention and treatment.
Contraindications
hepatic insufficiency
acute and chronic hepatitis
pancreatic dysfunction
porphyria
hemorrhagic diathesis
severe thrombocytopenia srdlkme urea umenea (urea) lamotrigine
lactation period
children under 3 years of age
hypersensitivity to valproic acid and its salts or components of the drug.
Precautions:
with anamnestic data on liver and pancreas diseases (including a family history)
with inhibition of bone marrow hematopoiesis (leukopenia, thrombocytopenia, anemia)
with renal disease in organic srdlp
for hypoproteinemia
for children with mental retardation.
Use in cases of impaired liver function
Contraindicated in severe impairment of liver function. With extreme caution, the drug should be prescribed if there is a history of liver disease.
Use in cases of impaired renal function
Patients with renal failure may require a dose reduction. The dose is established by monitoring the clinical condition of the patient, because plasma concentrations of valproic acid may not be sufficiently informative.
Use in children
Contraindication: children under 3 years of age (for tablets with prolonged action).
Use in elderly patients
Although the pharmacokinetics of valproic acid in the elderly may have their own characteristics, this is of limited clinical significance, and the dose should be determined by the clinical effect. Due to a decrease in binding to serum albumin, the proportion of unbound drug in plasma increases. This makes it expedient to more carefully select the dose of the drug in the elderly, with the possible use of smaller doses of the drug.
Use during pregnancy and lactation
Pregnancy should be avoided during treatment.
In animal experiments, the teratogenic effect of valproic acid was revealed. The frequency of development of neural tube defects in children born to women who took valproate in the first trimester of pregnancy is 1-2%. It is advisable in this regard, the use of folic acid preparations.
In the first trimester of pregnancy, Convulex treatment should not be started. If the pregnant woman is already receiving the drug, then due to the risk of increased seizures, treatment should not be interrupted.
The drug should be used in the lowest effective doses, avoiding combination with other anticonvulsants and, if possible, regularly monitoring the concentration of valproic acid in the plasma.
Special instructions
In connection with available reports of severe and fatal cases of liver failure and pancreatitis with the use of valproic acid preparations, the following should be borne in mind: the
high-risk group is infants and children up to 3 years old, 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 of
, cases of pancreatitis were observed regardless of the patient ² ¢s age and duration of treatment , although the risk of developing pancreatitis decreased with the age of the patient
, liver failure with pancreatitis increases the risk of death of early
I diagnosis (before the icteric stage) is mainly based on clinical observation – identifying early symptoms such as asthenia, anorexia, extreme fatigue, drowsiness, sometimes accompanied by vomiting and abdominal pain, a relapse of epileptic seizures against the background of constant antiepileptic therapy may be noted.
In such cases, you should immediately consult a doctor for a clinical examination and analysis of liver function.
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, the concentration of bilirubin, as well as the activity of amylase (every 3 months, especially when combined with other antiepileptic drugs) and a picture of peripheral blood, in particular blood platelets.
Patients who receive other antiepileptic drugs should be gradually transferred to valproic acid. reaching a clinically effective dose after 2 weeks, after which a gradual cancellation of other antiepileptic drugs is possible. In patients not treated with other antiepileptic drugs, a clinically effective dose should be reached after 1 week.
The risk of developing 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 complete blood count (including platelet count), determination of bleeding time, and coagulation parameters are necessary.
If an acute abdomen develops during treatment of a symptom complex, it is recommended that blood amylase activity be determined before acute surgery to exclude acute pancreatitis.
During treatment, possible distortion of the results of urinalysis in diabetes mellitus (due to an increase in the content of ketone bodies), indicators of thyroid function should be considered.
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 dyspeptic disorders, it is possible to take antispasmodics and enveloping agents.
Abrupt cessation of Convulex may result in more frequent seizures.
Influence on the ability to drive vehicles and operate machinery
During treatment, care must be taken when driving vehicles and engaging in other potentially dangerous activities, requiring increased concentration of attention and speed of psychomotor reactions.
Composition
1 ml
sodium valproate 300 mg
Excipients:
sodium saccharinate – 8.5 mg,
flavor with orange flavor – 2 mg,
hydrochloric acid 37% – qs up to pH 9.0, ss pH q – 0 sr.0.0 srdl srd.0 qp sr.0.0 ,
purified water – up to 1 ml.
Dosage and administration
Individual. For oral administration in adults and children weighing more than 25 kg, the initial dose is 10-15 mg / kg / day. Then the dose is gradually increased by 200 mg / day with an interval of 3-4 days until the clinical effect is achieved. The average daily dose is 20-30 mg / kg. For children weighing less than 25 kg and newborns, the average daily dose is 20-30 mg / kg.
Frequency of administration – 2-3 times / day with meals.
I / O (in the form of sodium valproate) is administered in a dose of 400-800 mg or drip at the rate of 25 mg / kg for 24, 36 and 48 hours. If necessary, simultaneous administration inside and / or in the first administration is carried out by / in infusion in a dose of 0.5-1 mg / kg / h 4-6 hours after the last oral administration.
Maximum doses: when taken orally for adults and children weighing more than 25 kg – 50 mg / kg / day. The use of a dose of more than 50 mg / kg / day is possible provided that the concentration of valproate in the blood plasma is controlled. With a plasma concentration of more than 200 mg / l, the dose of valproic acid should be reduced.
Capsules are taken orally, without chewing, 2-3 times / day, during or immediately after a meal, with a small amount of water.
Adults are prescribed an initial dose of 600 mg / day with a gradual increase in dose of 150-250 mg every 3 days until the clinical effect (the disappearance of seizures) is achieved.
The initial dose for monotherapy is 5-15 mg / kg / day, then the dose is gradually increased by 5-10 mg / kg per week.
The recommended daily dose is about 1-2 g, i.e. 20-25 mg / kg. If necessary, the dose can be increased to a maximum dose of 2.5 g / day (30 mg / kg).
The maximum dose is 30 mg / kg / day (in patients with an accelerated metabolism of valproic acid, the maximum dose can be increased to 60 mg / kg / day under the control of the concentration of valproic acid in the blood plasma).
When conducting combination therapy, the dose is 10-30 mg / kg / day, followed by an increase of 5-10 mg / kg per week.
Children with a body weight of more than 25 kg are prescribed in an initial dose of 300 mg / day (5-15 mg / kg / day), with a gradual increase of 5-10 mg / kg per week until the clinical effect (disappearance of seizures) is achieved, while the dose, as a rule, is 1-1.5 g / day (20-30 mg / kg / day).
The maximum dose is 30 mg / kg / day (in patients with an accelerated metabolism of valproic acid, the maximum dose can be increased to 60 mg / kg / day under the control of the concentration of valproic acid in the blood plasma).
For children with a body weight of 7.5-25 kg with monotherapy, the average dose is 15-45 mg / kg / day, the maximum is 50 mg / kg / day. With combination therapy – 30-100 mg / kg / day.
Average daily doses of Konvuleks
Patient body weight (kg) Dose (mg / day) Number of capsules 150 mg Number of capsules 300 mg Number of capsules 500 mg
7. 5-14 150-450 1-3 – –
14-21 300-600 2-4 1-2 –
21-32 600-900 4-6 2-3 –
32-50 900-1500 – 3-5 2-3
50-90 1500-2500 – – 3-5
Although the pharmacokinetics of valproic acid in the elderly may have their own characteristics, it has limited clinical significance, and the dose should be determined by the clinical effect. Due to a decrease in binding to serum albumin, the proportion of unbound drug in plasma increases. This makes it expedient to more carefully select the dose of the drug in the elderly, with the possible use of smaller doses of the drug.
In patients with renal failure, it may be necessary to reduce the dose of the drug. The dose should be selected according to the monitoring of the clinical condition, since plasma concentration indicators may not be sufficiently informative.
Side effects
In general, Convulex ® is well tolerated by patients. Side effects are possible mainly with a plasma concentration of the drug above 100 mg / l or with combination therapy.
From the digestive system: nausea, vomiting, gastralgia, decreased or increased appetite, diarrhea, hepatitis, constipation, pancreatitis, up to severe lesions with a fatal outcome (in the first 6 months of treatment, more often for 2-12 weeks.).
From the side of the central nervous system: tremors, diplopia, nystagmus, flickering flies before the eyes, changes in behavior, mood or mental state (depression, feeling tired, hallucinations, aggressiveness, hyperactive state, psychosis, unusual arousal, motor anxiety or irritability), ataxia, dizziness , drowsiness, headache, encephalopathy, dysarthria, enuresis, stupor, impaired consciousness, coma.
From the hemopoietic system: anemia, leukopenia, thrombocytopenia, decreased fibrinogen and platelet aggregation, leading to the development of hypocoagulation (accompanied by an increase in bleeding time, petechial hemorrhage, bruising, hematomas, bleeding).
From the side of metabolism: decrease or increase in body weight.
From the endocrine system: dysmenorrhea, secondary amenorrhea, breast enlargement, galactorrhea.
On the part of laboratory parameters: hypercreatininemia, hyperammonemia, hyperbilirubinemia, a slight increase in the activity of hepatic transaminases, LDH (dose-dependent).
Allergic reactions: skin rash, urticaria, angioedema, photosensitivity, malignant exudative erythema (Stevens-Johnson syndrome).
Other: peripheral edema, hair loss (usually restored after drug withdrawal).
Drug interaction
Contraindicated
combinations Mefloquine: risk of epileptic seizures due to increased metabolism of valproic acid and a decrease in its concentration in plasma and, on the other hand, the convulsive effect of mefloquine.
Hypericum perforatum: the risk of a decrease in the concentration of valproic acid in blood plasma.
Not recommended combinations
Lamotrigine: increased risk of severe skin reactions (toxic epidermal necrolysis). Valproic acid inhibits microsomal liver enzymes providing lamotrigine metabolism, which slows its T1 / 2 up to 70 hours in adults and up to 45-55 hours in children and increases the concentration in blood plasma. If a combination is necessary, careful clinical and laboratory monitoring is required.
Special precautions
Carbamazepine: Valproic acid increases the concentration of the active metabolite of carbamazepine in the plasma to 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 plasma concentrations of drugs and a possible review 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 enhances 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 determination of the level of anticonvulsants in the blood.
Phenytoin: changes in plasma phenytoin concentration are possible, phenytoin enhances the hepatic metabolism of valproic acid and reduces its concentration. Clinical observation, determination of the level of anticonvulsants in the blood, dosage changes if necessary are recommended.
clonazepam: the addition of valproic acid to clonazepam in isolated cases can lead to an increase in the severity of the abscess status.
Ethosuximide: valproic acid can both increase and decrease the concentration of ethosuximide in serum due to a change in its metabolism. Clinical observation, determination of the level of anticonvulsants in the blood, dosage changes if necessary are recommended.
Topiramate: increased risk of hyperammonemia and encephalopathy.
Felbamate: increased plasma concentration of valproic acid by 35-50%, with the risk of overdose. Clinical observation is recommended, determining the level of valproic acid in the blood, changing the dosage of valproic acid when combined with felbamate and after it is canceled.
Antipsychotics, MAO inhibitors, antidepressants, benzodiazepines: antipsychotics, tricyclic antidepressants, MAO inhibitors, lowering 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 plasma.
Zidovudine: Valproic acid increases the concentration of zidovudine in the plasma, which leads to an increase in its toxicity.
Carbapenems, monobactams: meropenem, panipenem, as well as aztreon and imipenem reduce the concentration of valproic acid in plasma, which can lead to a decrease in the anticonvulsant effect.
Combinations to consider
Acetylsalicylic acid: enhances the effects of valproic acid by displacing it from its association 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 when used together with vitamin K-dependent anticoagulants is necessary.
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 inhibition of bone marrow hematopoiesis.
Ethanol and hepatotoxic drugs: increase the likelihood of liver damage.
Other combinations
Oral contraceptives: valproic acid does not induce microsomal liver enzymes and does not reduce the effectiveness of hormonal oral contraceptives.
Overdose
Symptoms: nausea, vomiting, dizziness, diarrhea, dysfunction of breathing, muscular hypotension, hyporeflexia, miosis, coma.
Treatment: gastric lavage (not later than 10-12 h) followed by the appointment of activated charcoal, hemodialysis. Forced diuresis, function maintenance.
Storage conditions
The product should be stored out of the reach of children at a temperature not exceeding 30 ° C.
Shelf life
5 years.
Deystvuyushtee substance
Valyproevaya Chisloth
Pharmacy terms
prescription
Dosage form
drops for oral administration
Possible product names
CONVULEX 0.3 N100 CAPS enteric-soluble
CONVULEX 0.3 / 1ML 100ML DROPS
CONVULEX 0.3 / ML 100ML DROPS
Convulex 300ml / ml drops 300gml drops . soft X100 (R)
Herot Pharmacoitica GmbH, Germany p19rewductförtmöhf Germanyfröhtförtfrömtörfmacht Germany X, Germany
