KONVULSOFIN

Active material: Valproic Acid
When ATH: N03AG01
CCF: Anticonvulsants
ICD-10 codes (testimony): F31, G40
When CSF: 02.05.05
Manufacturer: AWD.pharma GmbH & Co.KG (Germany)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Pills white with a faint yellowish tinge, round, flat, with bevelled edges and scored on one side.

Excipients: potato starch, gelatin, silicon dioxide, talc, magnesium stearate.

100 PC. – plastic bottles (1) – packs cardboard.

Pharmacological action

The antiepileptic drug. It has anticonvulsant, central muscle relaxant and sedative effect.

The mechanism of action is associated with an increase in the content of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the CNS by inhibiting the enzyme GABA-transferase, and decreasing GABA reuptake in brain tissue. This reduces anxiety and convulsive readiness of motor areas of the brain.

According to another hypothesis, the drug acts on the postsynaptic sites, simulating or enhancing the inhibitory effect of GABA. Possible direct effect on the activity of the membrane due to changes in potassium conductance.

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

Highly effective in absence seizures and temporal psevdoabsansah, few – during psychomotor seizures.

Pharmacokinetics

Absorption

The extent of absorption of the high, bioavailability – 100%. C_max achieved through 3-4 no. Simultaneous food intake slightly decreases the rate of absorption.

Distribution

C_ss achieved at 2-4 day reception (It depends on the intervals between doses). Therapeutic plasma concentrations fluctuate within 50-150 mg / l. Binding to plasma proteins is 90-95% at plasma concentrations to 50 mg / l and reduced to 80-85% at concentrations 50-100 mg / l. V_d – 0.2 l / kg. It penetrates through the placental barrier and the blood-brain barrier. Provided with breast milk (concentration in breast milk is 1-10% concentration in maternal plasma). The content in cerebrospinal fluid correlates with the unbound fraction of proteins.

Metabolism

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

Deduction

T_1/2 is 12-16 no. Valproic Acid (1-3%) and its metabolites (in the form of conjugates, oxidation products, incl. ketometabolitov) the kidneys; small amounts are excreted in the feces and expired air.

Pharmacokinetics in special clinical conditions

When uremia, hypoproteinemia and liver cirrhosis plasma protein binding 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 hepatic function, in elderly patients and children under the age of 18 mes T_1/2 can be much longer the.

Testimony

- Epilepsy of various origins: generalized and partial seizures;

- Epileptic seizures on the background of organic brain disorders;

- Changes in the nature and behavior (due to epilepsy);

- Manic depression with bipolar course, is not amenable to treatment with drugs, lithium, or other drugs;

- Specific syndromes (Vesta, Lennox-Gastaut syndrome).

Dosage regimen

Treatment Konvulsofinom start with low doses of the drug, They are then gradually increased until the optimal dosage supporting.

The initial dose of monotherapy Konvulsofina 5-10 mg / kg body weight. Every 4-7 days the dose is increased by 5 mg. Average daily dose adults and elderly and senile is 20 mg / kg body weight, to older teens 14 years – 25 mg / kg body weight, to children aged 3 to 14 years – 30 mg / kg body weight.

If Konvulsofin administered with other antiepileptic drugs, or to replace the previous formulation, the dose previously received the drug, especially phenobarbital, immediately lower.

Full transition to treatment Konvulsofinom produce slow, gradually reducing the dose previous drug.

Usually guided by the following indicative outline application Konvulsofina:

At impaired renal function the daily dose should be reduced Konvulsofina.

The daily dose distribute 2-4 admission.

The drug should be taken during or after a meal, liquid squeezed small amounts of liquid.

Side effect

CNS: tremor; rarely – behavior changes, mood or mental state (depression, feeling tired, hallucinations, aggressiveness, hyperactive state, psychoses, unusual excitement, restlessness or irritability), ataxia, dizziness, drowsiness, headache, encephalopathy, dysarthria, enuresis, stupor, disturbance of consciousness, coma.

From the senses: diplopia, nistagmo, twinkle “muşek” before your eyes, hearing disorder.

From the digestive system: nausea, vomiting, gastralgia, Anorexia or increased appetite, diarrhea, hepatitis, slight increase in liver transaminases, LDH, giperʙiliruʙinemija; rarely – constipation, pancreatitis (up to heavy defeats fatal in the first 6 months of treatment, often at 2-12 weeks).

From the hematopoietic system: anemia, leukopenia.

From the blood coagulation system: thrombocytopenia, reduction of fibrinogen, prolonged bleeding, petechiae, bruising, hematoma, increased bleeding.

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

Dermatological reactions: photosensitivity, alopecia.

From the urinary system: giperkreatininemiя, ammoniemia.

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

Other: increase or decrease in body weight, peripheral edema, giperglicinemiя.

Contraindications

- Liver failure;

- Acute and chronic hepatitis;

- Dysfunction of the pancreas;

- Porphyria;

- Gyemorragichyeskii diatyez;

- Thrombocytopenia;

- Children up to age 3 years;

- History of liver disease;

- Hypersensitivity to the drug.

Pregnancy and lactation

In pregnancy, the use of Konvulsofina possible only under strict indications, after careful assessment of the expected benefit of therapy for the mother and the possible risk to the fetus.

When using Konvulsofina in early pregnancy increases the risk of cleft neural tube in the embryo (myelomeningocele). At the same time can be marked other fetal abnormalities. The risk of fetal anomalies is increased by combined use Konvulsofina with other antiepileptic drugs.

If it is impossible to refuse conducting therapy Konvulsofinom I trimester of drug administered in the lowest dose, and between 20 and 40 day of pregnancy daily dose partitioned into several smaller single doses during the day. It is necessary to regularly monitor the concentration of valproic acid in blood plasma. With the purpose of early diagnosis of fetal anomalies recommended ultrasound studies and alpha₁ -fetoproteinovy ​​test.

Valproic acid is excreted in breast milk in small amounts, do not pose a danger to the child, so, usually, cessation of breastfeeding during therapy is not required Konvulsofinom.

Cautions

With extreme caution and under close medical supervision It should be prescribed the drug for bone marrow aplasia, blood dyscrasia, organic brain diseases, gipoproteinemii, renal failure.

The transition from the treatment of other anticonvulsant therapy Konvulsofinom produce slow, achieving a clinically effective dose for 2 weeks and gradually lowering the dose of the drug last until canceled. Patients, not received prior treatment with antiepileptic drugs, clinically effective dose should be achieved through 1 week.

Side effects usually occur during the combination therapy, than monotherapy Konvulsofinom.

Before surgical procedures to patients, receiving Konvulsofin, should determine the number of platelets, bleeding time, coagulation parameters.

With the development in patients receiving symptom Konvulsofina “acute abdomen” before surgery is recommended to determine the level of amylase in the blood to avoid acute pancreatitis.

With the development of spontaneous bruising and bleeding and the appearance of symptoms, weakness, lethargic, puffiness, vomiting and jaundice, should immediately stop using the product.

It should be taken into account, that while taking Konvulsofina possible false positive reaction for the presence of ketones in the urine, distortions in the functioning of the thyroid gland.

During treatment Konvulsofinom no admission of ethanol-containing beverages.

Monitoring of laboratory parameters

The therapy Konvulsofinom need to periodically monitor the activity of liver transaminases, bilirubin, peripheral blood picture, fibrinogen level in blood plasma, thromboplastin time, the level of alpha-amylase in urine (every 3 of the month).

Use in Pediatrics

Children (especially before 2 years) increased risk of severe hepatic impairment in patients receiving Konvulsofina.

Effects on ability to drive vehicles and management mechanisms

The drug can impair psychomotor speed reactions and ability to concentrate, so patients, receiving Konvulsofin, It should refrain from potentially hazardous activities.

Overdose

Symptoms: nausea, vomiting, dizziness, diarrhea, respiratory dysfunction, hypomyotonia, giporefleksiя, mioz, coma (EEG slow waves, and an increase in the background activity).

Treatment: gastric lavage (not later than 10-12 no), administration of activated charcoal, diurez, maintaining vital functions, hemodialysis.

Drug Interactions

In an application Konvulsofina with ethanol and other drugs, CNS depressants, may increase CNS depression.

In an application Konvulsofina and other antiepileptic drugs, neuroleptics, Antidepressants, trankvilizatorov, ʙarʙituratov, MAO inhibitors, timoleptikov may enhance their effects, incl. and by.

Simultaneous treatment with tricyclic antidepressants Konvulsofinom (imipramine) or phenytoin may cause generalized seizures, clonazepam – absence.

In an application Konvulsofina with other anticonvulsants (phenobarbital, phenytoin, Carbamazepine, mefloxin) possible reduction of valproic acid in serum (acceleration of its metabolism).

With simultaneous use of anticoagulants and Konvulsofina (coumarin and derivatives indandiona, Heparin, thrombolytic agents and antiplatelet agents) a mutual potentiation effect on blood clotting and increase the risk of bleeding.

In an application with Konvulsofinom, in addition to the CNS depression, tricyclic antidepressants, Bupropion, klozapyn, haloperidol, loxapine, maprotilin, molindon, MAO inhibitors, fenotiazinы, pimozid, thioxanthenes may reduce the threshold for seizure activity.

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

In an application Konvulsofina c hepatotoxic drugs and ethanol may increase the toxic effect on the liver Konvulsofina.

In an application Konvulsofina with salicylates is amplified its effects (Due to the displacement of proteins).

In an application with barbiturates Konvulsofina and primidone is an increase in their concentration in the blood plasma.

Konvulsofin increases T_1/2 lamotryhyna to 70 hours in adults and up 45-55 no – children.

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

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

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

Conditions and terms

The drug should be stored at a temperature no higher than 30 ° C, out of reach of children. Shelf life – 5 years.

Conditions of supply of pharmacies

The drug is released under the prescription.