KONVULEKS

Active material: Valproic Acid
When ATH: N03AG01
CCF: Anticonvulsants
ICD-10 codes (testimony): F31, G40, R25.2
When CSF: 02.05.05
Manufacturer: Gerot Pharmazeutika GmbH (Austria)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Soft Capsules gelatin pink, enteric coated; on the capsule napechatka black ink “150”.

Excipients: sorbitol (Carrion 83), glycerol 85%, gelatin, Titanium dioxide, iron oxide red (E172), hydrochloric acid 25%, shellac, iron oxide black (E172), phthalate gipromellozы, diʙutilftalat.

10 PC. – blisters (10) – packs cardboard.

Soft Capsules gelatin pink, enteric coated; on the capsule napechatka black ink “300”.

Excipients: sorbitol (Carrion 83), glycerol 85%, gelatin, Titanium dioxide, iron oxide red (E172), hydrochloric acid 25%, shellac, iron oxide black (E172), phthalate gipromellozы, diʙutilftalat.

20 PC. – blisters (5) – packs cardboard.

Capsules Soft gelatin pink, enteric coated; on the capsule napechatka black ink “500”.

Excipients: sorbitol (Carrion 83), glycerol 85%, gelatin, Titanium dioxide, iron oxide red (E172), hydrochloric acid 25%, shellac, iron oxide black (E172), phthalate gipromellozы, diʙutilftalat.

10 PC. – blisters (10) – packs cardboard.

Sustained-release tablets, coated white, Oval, lenticular, vanilla, with Valium and engraving “SS3” one side; the cross-section – white.

Excipients: citric acid monohydrate, ethyl cellulose, eudragit RS30D, Talcum cleared, silica colloidal anhydrous, magnesium stearate, eudragit L30D, diʙutilftalat, carmellose sodium, macrogol 6000, Titanium dioxide, vanillin, simethicone.

50 PC. – plastic bottles (1) – packs cardboard.
50 PC. – glass bottles (1) – packs cardboard.

Sustained-release tablets, coated white, Oval, lenticular, vanilla, with Valium and engraving “CC5” one side; the cross-section – white.

Excipients: citric acid monohydrate, ethyl cellulose, eudragit RS30D, Talcum cleared, silica colloidal anhydrous, magnesium stearate, eudragit L30D, diʙutilftalat, carmellose sodium, macrogol 6000, Titanium dioxide, vanillin, simethicone.

50 PC. – plastic bottles (1) – packs cardboard.
50 PC. – glass bottles (1) – packs cardboard.

Drops for intake in the form of colorless or slightly yellowish solution.

Excipients: Purified water.

100 ml – glass bottles (1) – packs cardboard.

Syrup for children colorless or slightly yellow, with peach flavor and a sweet peach flavor.

Excipients: Sodium hydroxide, likazin 80/55, sodium saccharin, sodium cyclamate, metilgidroksiʙenzoat, propyl, sodium chloride, raspberry flavors (9/372710) and Peach (9/030307), Purified water.

100 ml – vials of dark glass (1) complete with a dosing cup – packs cardboard.

Pharmacological action

The antiepileptic drug. The mechanism of action is due to inhibition of the enzyme GABA-transferase and increased content of GABA in the CNS. GABA prevents pre- and postsynaptic discharges and thus prevents the spread of seizure activity in the CNS. Besides, in the mechanism of action of the drug plays a significant role in the effects of valproic acid GABA receptors_A, as well as the influence on the voltage-dependent Na-channels. According to another hypothesis,, valproic acid acts on the postsynaptic sites, simulating or enhancing the inhibitory effect of GABA. Possible direct effect on the activity of membrane associated with changes in the permeability of potassium.

It improves mood and mental state of the patients, It has antiarrhythmic activity.

Pharmacokinetics

Absorption

Valproic acid is rapidly and almost completely absorbed from the gastrointestinal tract, oral bioavailability is about 100%. Food intake did not reduce the rate of absorption. C_max in plasma observed after 3-4 no. Therapeutic concentrations of valproic acid in blood plasma is 50-100 mg / l.

Prolonged form is characterized by the slow absorption, lower (on 25%), but a more stable plasma concentration between 4 and 14 no.

Distribution

C_ss achieved at 2-4 day treatment, depending on the intervals between doses doses.

When the concentration in the blood plasma before 50 mg / l of valproic acid binding to plasma proteins is 90-95%, at concentrations 50-100 mg / l – 80-85%.

Values ​​of concentrations in cerebrospinal fluid are correlated with the non-protein fraction of the active substance. Valproic acid crosses the placental barrier, excreted in breast milk. Concentration in breast milk is 1-10% plasma concentrations of the mother.

Metabolism

Valproic acid is metabolized in the liver by oxidation and conjugation with glucuronic acid.

Deduction

Valproic Acid (1-3% dose) and its metabolites are excreted by the kidneys, small amounts – with feces and expired air. T_1/2 monotherapy in healthy volunteers is 8-20 no.

Pharmacokinetics in special clinical situations

When uremia, gipoproteinemii cirrhosis and valproic acid binding to plasma proteins is reduced.

When combined with other drugs T_1/2 can be 6-8 h due to the induction of metabolic enzymes. In patients with impaired liver function and the elderly may be a significant increase in T_1/2.

In elderly patients, due to reduced binding of the active substance with serum albumin may increase the plasma levels of unbound drug.

Testimony

- Epilepsy of any origin;

- Epileptic seizures (incl. generalized and partial, and on the background of organic brain disease);

- Conduct disorder, associated with epilepsy;

- Febrile convulsions in children;

- Manic-depressive syndrome with bipolar course, is not amenable to treatment with drugs, lithium, or other drugs.

Dosage regimen

Adults administered in an initial dose of 600 mg / day with a gradual increase every 3 day to achieve the clinical effect (the disappearance of seizures).

The initial dose of monotherapy 5-15 mg / kg / day, then gradually increase the dose to 5-10 mg / kg per week.

Average daily dose – about 1-2 g, ie. 20-30 mg / kg. If necessary, the dose may be increased to 2.5 g / day.

The maximum dose is 30 mg / kg / day (It can be increased to 60 mg / kg / day under the control of the concentration of valproic acid in blood plasma).

In combination therapy, the dose is 10-30 mg / kg / day with subsequent increase of 5-10 mg / kg per week.

Children weighing more 25 kg administered in an initial dose of 300 mg / day with gradual increase to achieve a clinical effect (the disappearance of seizures), at this dose, usually, is 20-30 mg / kg / day.

The initial dose in monotherapy – 5-15 mg / kg / day, then gradually increase the dose to 5-10 mg / kg per week.

The maximum dose is 30 mg / kg / day (It can be increased to 60 mg / kg / day under the control of the concentration of valproic acid in blood plasma).

To children weighing 7.5-25 kg monotherapy average dose is 15-45 mg / kg / day, maximum – 50 mg / kg / day. Combined therapy – 30-100 mg / kg / day.

In children weighing from 7.5 to 17 kg preferred use of the drug in capsule form (150 mg or 300 mg), drops, Syrup.

Average dose Konvuleksa^® in the form of capsules are shown in Table 1.

Table 1

Average dose Konvuleksa^® in the form of droplets and are presented in Table syrup 2.

Table 2

Patients with renal insufficiency may require dose reduction. Dose set while monitoring the patient's clinical condition, tk. values ​​of valproic acid concentration in blood plasma can not be sufficiently informative.

In elderly patients the dose should be defined more carefully, taking into account the clinical effect; It may require the use of the drug in smaller doses.

The daily dose in capsule form, Drops for oral administration and syrup to distribute 2-3 admission; a daily dose in the form of tablets with prolonged effect on partitioned 1-2 admission. The drug is taken regardless of meals.

Capsules and tablets with prolonged action taken without chewing, drinking a small amount of liquid. Drops and syrup to take small amounts of liquid.

Side effect

Development of possible side effects mainly in the drug concentration in blood plasma more 100 mg / kg, or in combination therapy.

From the digestive system: nausea, vomiting, gastralgia, Anorexia or increased appetite, diarrhea, hepatitis; rarely – constipation, pancreatitis, up to heavy defeats fatal (first 6 months of treatment, often on 2-12 Sun.).

CNS: possible tremors, diplopia, nistagmo, twinkle “muşek” before your eyes; rarely – behavior changes, mood or mental state (depression, feeling tired, hallucinations, aggressiveness, hyperactive state, psychoses, unusual excitement, restlessness or irritability), ataxia, dizziness, drowsiness, headache, dysarthria, stupor, disturbance of consciousness, coma.

From the hematopoietic system: possible anemia, leukopenia, thrombocytopenia, reduction of fibrinogen, platelet aggregation and blood coagulation, accompanied by a prolongation of bleeding time, petechiae, bruises, gematomami, bleeding.

Metabolism: may increase or decrease in body weight.

On the part of the endocrine system: possible dysmenorrhea, secondary amenorrhea, breast enlargement, galactorrhea.

From the laboratory parameters: giperkreatininemiя, ammoniemia, giperʙiliruʙinemija, slight increase in liver transaminases, LDH (dose-dependent).

Allergic reactions: possible skin rash, hives, angioedema, photosensitivity, Stevens-Johnson syndrome.

Other: swelling, hair loss (usually, recovered after drug withdrawal).

Side effects are possible mainly at the level of valproic acid in blood plasma above 100 mg / l, or in combined therapy.

Contraindications

- Severe liver;

- Severe violations of the pancreas;

- Porphyria;

- Gyemorragichyeskii diatyez;

- Vыrazhennaya thrombocytopenia;

- I trimester of pregnancy;

- Lactation (breast-feeding);

- Children up to age 3 years (for tablets with prolonged effect);

- Hypersensitivity to valproic acid.

FROM caution should be prescribed when specifying a history of liver disease and pancreatic cancer, destruction of the bone marrow; renal impairment; patients with congenital enzimopaty; mentally retarded children; with organic brain lesions; when hypoproteinemia.

Pregnancy and lactation

Konvuleks^® contraindicated for use in the I trimester of pregnancy.

During the ensuing pregnancy due to the risk of deterioration of the treatment should not be interrupted. Konvuleks^® It should be used in the smallest effective doses, Avoid combination with other anticonvulsants, and regularly monitor the level of valproic acid in plasma.

If necessary, use Konvuleksa^® lactation should decide the issue of termination of breastfeeding.

Women of childbearing age During treatment should use reliable methods of contraception.

IN experimental studies established teratogenic effect of the drug.

The incidence of neural tube defects in children, born to women, Accepted valproate in the I trimester of pregnancy, is 1-2%. In this connection it is expedient to use during pregnancy folic acid.

Cautions

Patients, who are receiving other antiepileptic drugs, transfer to the reception Konvuleksa^® should be gradual, achieving a clinically effective dose through 2 Sun, then perhaps the gradual abolition of other antiepileptics. Patients, not treated with other antiepileptic drugs, clinically effective dose should be achieved through 1 week of therapy.

During the combined anticonvulsant therapy increases the risk of side effects from the liver.

Patients, receiving Konvuleks^®, before surgery required blood count (incl. platelet count), determination of bleeding time, coagulation parameters.

In the event of symptoms during treatment “acute abdomen” before surgery is recommended to determine the level of amylase in the blood to avoid acute pancreatitis.

It should be taken into account, against the background of the treatment may be distorted results of urine tests for patients with diabetes (due to higher content of ketoproduktov), indicators of thyroid function.

To reduce the risk of dyspepsia can receive antispasmodics and envelop funds.

Patients should be warned of the need to consult with your doctor about the advisability of continuing or stopping treatment with the development of any acute serious side effects.

Sudden discontinuation Konvuleksa^® could lead to more frequent seizures.

During the period of use of the drug should avoid alcohol.

Monitoring of laboratory parameters

Before the start of therapy and during treatment should regularly monitor liver function (the activity of hepatic transaminases, bilirubin), peripheral blood picture, the state of the blood coagulation system, amylase (every 3 Months, especially in combination with other antiepileptic drugs).

Use in Pediatrics

In applying the drug in children increases the risk of side effects from the liver.

Effects on ability to drive vehicles and management mechanisms

Patients, receiving Konvuleks^®, It should refrain from activities potentially hazardous activities, require increased attention and psychomotor speed reactions.

Overdose

Symptoms: nausea, vomiting, dizziness, diarrhea, respiratory dysfunction, hypomyotonia, giporefleksiя, mioz, coma.

Treatment: gastric lavage (not later than 10-12 no) followed by the appointment of activated carbon, hemodialysis. Forced diuresis, the maintenance of respiratory function and the cardiovascular system.

Drug Interactions

Pharmacodynamic interactions

With simultaneous use of valproic acid drugs, have a depressing effect on the central nervous system (incl. tricyclic antidepressants, MAO inhibitors and antipsychotic drugs), and ethanol may be increased CNS depression.

Hepatotoxic agents (incl. ethanol) increases the risk of liver damage.

Preparations, lowering the seizure threshold (incl. tricyclic antidepressants, MAO inhibitors, antipsychotics), reduce the effectiveness of valproic acid.

Konvuleks^® enhances the effects of (incl. side) other anticonvulsants (phenytoin, lamotrigine), Antidepressants, antipsychotics, trankvilizatorov, ʙarʙituratov, MAO inhibitors, thymoleptics, ethanol. When using valproate in patients, receiving clonazepam, in a few cases, there was increased expression of the status of absence.

Pharmacokinetic interactions

With simultaneous use of valproic acid with barbiturates or primidone marked increase in their concentration in the blood plasma. Because inhibition influenced valproic acid and liver enzymes slowing metabolism lamotrigine it increases its T_1/2 to 70 hours in adults and up 45-55 no – children.

Valproic acid reduces the clearance of zidovudine by 38%, while its T_1/2 not changed.

While the use of salicylates has been increasing effects of valproic acid due to displacement from its association with plasma proteins. Konvuleks^® enhances the effects of antiplatelet agents (acetylsalicylic acid) and anticoagulants.

In combination with pentobarbital, phenytoin, karʙamazepinom, mefloquine reduced the content of valproic acid in serum (accelerate metabolism).

Felbamate increases the concentration of valproic acid in blood plasma 35-50% (require dose adjustment).

Valproic acid causes no induction of liver enzymes, and does not reduce the effectiveness of oral contraceptives.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. Capsules, Drops for oral administration, Syrup should be stored in a dry, dark place at a temperature of 15 ° to 25 ° C. Shelf life – 5 years.

Sustained-release tablets should be stored at temperatures below 25 ° C. Shelf life – 3 year.