Convulsofin^® (Tablets) Instructions for Use

ATC Code

N03AG01 (Valproic acid)

Active Substance

Valproic acid (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Anticonvulsant drug

Pharmacotherapeutic Group

Anticonvulsant agent

Pharmacological Action

Antiepileptic drug. It has anticonvulsant, central muscle relaxant and sedative effects.

The mechanism of action is associated with an increase in the content of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the central nervous system due to inhibition of the GABA-transaminase enzyme, as well as a decrease in the reuptake of GABA in the brain tissues. This reduces the excitability and convulsive readiness of the motor zones of the brain.

According to another hypothesis, the drug acts on the sites of postsynaptic receptors, mimicking 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 and has antiarrhythmic activity.

It is highly effective in absence and temporal pseudo-absence seizures, but less effective in psychomotor seizures.

Pharmacokinetics

Absorption

The degree of absorption is high, bioavailability is 100%. C_max is reached in 3-4 hours. Simultaneous food intake slightly reduces the rate of absorption.

Distribution

C_ss is reached on days 2-4 of administration (depends on the intervals between doses). Therapeutic plasma concentrations range from 50-150 mg/L. Binding to plasma proteins is 90-95% at plasma concentrations up to 50 mg/L and decreases to 80-85% at concentrations of 50-100 mg/L. V_d is 0.2 L/kg. It penetrates the placental barrier and the blood-brain barrier. It is excreted in breast milk (the concentration in breast milk is 1-10% of the concentration in maternal plasma). The content in the cerebrospinal fluid correlates with the value of the fraction not bound to proteins.

Metabolism

It is metabolized by glucuronidation and oxidation in the liver with the formation of hydroxylated derivatives of valproic acid.

Excretion

T_1/2 is 12-16 hours. Valproic acid (1-3%) and its metabolites (in the form of conjugates, oxidation products, including ketometabolites) are excreted by the kidneys; small amounts are excreted in the feces and exhaled air.

Pharmacokinetics in special clinical situations

In uremia, hypoproteinemia and liver cirrhosis, binding to plasma proteins is reduced.

When combined with other drugs, T_1/2 can be 6-8 hours due to induction of metabolic enzymes.

In patients with impaired liver function, in elderly patients and in children under 18 months of age, T_1/2 can be significantly longer.

Indications

• Epilepsy of various origins: generalized and partial seizures;
• Epileptic seizures against the background of organic brain diseases;
• Changes in character and behavior (due to epilepsy);
• Manic-depressive psychosis with bipolar course, not amenable to treatment with lithium preparations or other drugs;
• Specific syndromes (West, Lennox-Gastaut).

ICD codes

Dosage Regimen

Tablets

Treatment with Convulsofin^® is started with low doses of the drug, which are then gradually increased to optimal maintenance doses.

The initial dose of Convulsofin^® in monotherapy is 5-10 mg/kg of body weight. This dose is increased by 5 mg every 4-7 days. The average daily dose for adults and elderly and senile persons is 20 mg/kg of body weight, for adolescents over 14 years old – 25 mg/kg of body weight, for children aged 3 to 14 years – 30 mg/kg of body weight.

If Convulsofin^® is prescribed together with other antiepileptic drugs or to replace a previous drug, the dose of the previously taken drug, especially phenobarbital, is immediately reduced.

The complete transition to treatment with Convulsofin^® is done slowly, gradually reducing the dose of the previous drug.

The following approximate scheme for the use of Convulsofin^® is usually followed:

In case of impaired renal function, the daily dose of Convulsofin^® should be reduced.

The daily dose is divided into 2-4 doses.

The drug should be taken during or after meals, without chewing and with a small amount of liquid.

Adverse Reactions

From the central nervous system tremor; rarely – changes in behavior, mood or mental state (depression, feeling of fatigue, hallucinations, aggressiveness, hyperactive state, psychoses, unusual agitation, motor restlessness or irritability), ataxia, dizziness, drowsiness, headache, encephalopathy, dysarthria, enuresis, stupor, impaired consciousness, coma.

From the sense organs diplopia, nystagmus, flickering “flies” before the eyes, hearing impairment.

From the digestive system nausea, vomiting, gastralgia, anorexia or increased appetite, diarrhea, hepatitis, slight increase in the activity of hepatic transaminases, LDH, hyperbilirubinemia; rarely – constipation, pancreatitis (up to severe lesions with a fatal outcome in the first 6 months of treatment, more often on the 2nd-12th week).

From the hematopoietic system anemia, leukopenia.

From the blood coagulation system thrombocytopenia, decreased fibrinogen content, prolonged bleeding time, petechial hemorrhages, bruising, hematomas, increased bleeding.

Allergic reactions skin rash, urticaria, angioedema, Stevens-Johnson syndrome.

Dermatological reactions photosensitivity, alopecia.

From the urinary system hypercreatininemia, hyperammonemia.

From the endocrine system dysmenorrhea, secondary amenorrhea, breast enlargement, galactorrhea.

Other increase or decrease in body weight, peripheral edema, hyperglycinemia.

Contraindications

• Hepatic insufficiency;
• Acute and chronic hepatitis;
• Impaired pancreatic function;
• Porphyria;
• Hemorrhagic diathesis;
• Thrombocytopenia;
• Children under 3 years of age;
• History of liver disease;
• Hypersensitivity to the drug.

Use in Pregnancy and Lactation

During pregnancy, the use of Convulsofin^® is possible only for strict indications, after a thorough assessment of the expected benefit of therapy for the mother and the possible risk to the fetus.

When using Convulsofin^® in the early period of pregnancy, the risk of non-closure of the neural tube in the embryo (myelomeningocele) increases. Along with this, other fetal developmental anomalies may be noted. The risk of fetal developmental anomalies increases with the combined use of Convulsofin^® with other antiepileptic drugs.

If it is impossible to refuse therapy with Convulsofin^® in the first trimester, the drug is prescribed in the lowest doses, and between the 20th and 40th day of pregnancy, the daily dose is divided into several small single doses during the day. It is necessary to regularly monitor the concentration of valproic acid in the blood plasma. For early diagnosis of fetal developmental anomalies, it is recommended to perform ultrasound examinations and an alpha₁-fetoprotein test.

Valproic acid is excreted in breast milk in insignificant amounts that do not pose a danger to the child, therefore, as a rule, breastfeeding cessation during therapy with Convulsofin^® is not required.

Use in Hepatic Impairment

Contraindicated in hepatic insufficiency, history of liver disease.

Use in Renal Impairment

In case of impaired renal function, the daily dose of Convulsofin^® should be reduced.

Pediatric Use

The drug is contraindicated in children under 3 years of age.

Special Precautions

With special caution and under careful medical supervision, the drug should be prescribed for bone marrow aplasia, pathological changes in the blood, organic brain diseases, hypoproteinemia, renal failure.

The transition from treatment with another anticonvulsant drug to therapy with Convulsofin^® is done slowly, achieving a clinically effective dose within 2 weeks and gradually reducing the dose of the previous drug until its withdrawal. In patients who have not received prior treatment with antiepileptic drugs, the clinically effective dose should be reached after 1 week.

Side effects occur more often during combination therapy than during monotherapy with Convulsofin^®.

Before surgical manipulations, patients taking Convulsofin^® should determine the platelet count, bleeding time, and coagulogram parameters.

If a symptom complex of “acute abdomen” develops while taking Convulsofin^®, it is recommended to determine the level of amylase in the blood before starting surgery to exclude acute pancreatitis.

If spontaneous hematomas and bleeding develop and symptoms such as weakness, lethargy, swelling, vomiting and jaundice occur, the use of the drug should be stopped immediately.

It should be taken into account that while taking Convulsofin^®, false-positive reactions to the presence of ketone bodies in the urine and distortion of thyroid function indicators are possible.

During treatment with Convulsofin^®, the intake of ethanol-containing drinks is not allowed.

Control of laboratory parameters

During therapy with Convulsofin^®, it is necessary to periodically monitor the activity of hepatic transaminases, bilirubin level, peripheral blood picture, plasma fibrinogen level, thromboplastin time, and the level of alpha-amylase in the urine (every 3 months).

Use in pediatrics

In children (especially under 2 years old) there is an increased risk of developing severe liver dysfunction while taking Convulsofin^®.

Effect on the ability to drive vehicles and mechanisms

The drug may reduce the speed of psychomotor reactions and the ability to concentrate, so patients taking Convulsofin^® should refrain from potentially hazardous activities.

Overdose

Symptoms nausea, vomiting, dizziness, diarrhea, respiratory dysfunction, muscle hypotonia, hyporeflexia, miosis, coma (on EEG, an increase in slow waves and background activity).

Treatment gastric lavage (no later than 10-12 hours), intake of activated charcoal, forced diuresis, maintenance of vital functions, hemodialysis.

Drug Interactions

With simultaneous use of Convulsofin^® with ethanol and other drugs that depress the central nervous system, increased depression of the central nervous system is possible.

With simultaneous use of Convulsofin^® and other antiepileptic drugs, neuroleptics, antidepressants, tranquilizers, barbiturates, MAO inhibitors, thymoleptics, their effects, including side effects, may be enhanced.

Simultaneous administration of tricyclic antidepressants (imipramine) or phenytoin with Convulsofin^® may cause generalized epileptic seizures, and clonazepam may cause absence seizures.

With simultaneous use of Convulsofin^® with other anticonvulsant drugs (phenobarbital, phenytoin, carbamazepine, mefloquine), a decrease in the content of valproic acid in the serum (acceleration of its metabolism) is possible.

With simultaneous use of Convulsofin^® and anticoagulants (coumarin and indandione derivatives, heparin, thrombolytic agents and antiplatelet agents), mutual potentiation of the effect on the blood coagulation system occurs and the risk of bleeding increases.

With simultaneous use with Convulsofin^®, in addition to CNS depression, tricyclic antidepressants, bupropion, clozapine, haloperidol, loxapine, maprotiline, molindone, MAO inhibitors, phenothiazines, pimozide, thioxanthenes may lower the threshold of convulsive activity.

Convulsofin^® does not cause induction of hepatic enzymes and does not reduce the effectiveness of oral contraceptives.

With simultaneous use of Convulsofin^® with hepatotoxic drugs and ethanol, the toxic effect of Convulsofin^® on the liver may be enhanced.

With simultaneous use of Convulsofin^® with salicylates, its effects are enhanced (displacement from protein binding).

With simultaneous use of Convulsofin^® with barbiturates and primidone, the concentration of the latter in the blood plasma increases.

Convulsofin^® increases the T_1/2 of lamotrigine to 70 hours in adults and to 45-55 hours in children.

Convulsofin^® reduces the clearance of zidovudine by 38%, while its T_1/2 does not change.

Felbamate increases the plasma concentration of valproic acid by 35-50%.

Valproic acid may also affect the metabolism and binding to plasma proteins of other drugs (for example, codeine).

Storage Conditions

The drug should be stored at a temperature not exceeding 30°C (86°F), in a place inaccessible to children.

Shelf Life

Shelf life – 5 years.

Pharmacy dispensing terms

The drug is dispensed by prescription.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.