Index of drugs

Monotherapy of partial or partial seizures in patients from 16 years of age with newly diagnosed epilepsy. Adjunctive therapy: partial or partial seizures secondary generalization in adults, children and infants from 1 month of age with epilepsy; myoclonic seizures in adults and adolescents from 12 years of age with juvenile myoclonic epilepsy; tonic-clonic seizures originally generalized in adults and adolescents from 12 years of age with idiopathic generalized epilepsy.

1 tabl powl. contains 250 mg, 500 mg, 750 mg or 1000 mg levetiracetam. Table. powl. 750 mg contain sunset yellow orange (E110).

Antiepileptic drug - a pyrrolidone derivative. The mechanism of action of levetiracetam is not fully understood, it seems to be different from the way in which currently available antiepileptic drugs are available. Findingsin vitro andin vivo indicate that levetiracetam does not change the basic properties of the cell or normal neurotransmission processes. researchin vitro showed that levetiracetam affects the concentration of Ca²⁺ in neurons, partially inhibiting Ca currents²⁺ N type and limiting the release of Ca ions²⁺ stored inside neurons. In addition, it partly removes the inhibition of GABA-giculated pigs and Glycine induced by zinc and beta-carboline. In addition, it appears that the action of antiepileptic levetiracetam may be affected by interaction with the synaptic vesicle protein 2A. Following oral administration, levetiracetam is rapidly absorbed from the gastrointestinal tract, reaching C_max after 1.3 h. The absolute bioavailability after oral administration is almost 100%. The steady state concentration is reached after 2 days, in the case of a 2 times daily dosing regimen. Less than 10% of the drug is bound to plasma proteins. In humans, levetiracetam is not extensively metabolised. The main metabolism pathway (24% of the dose) is the enzymatic hydrolysis of the acetamide group in which the cytochrome P-450 enzymes do not participate. T_0,5 in adults is 7 ± 1 h and does not change depending on the dose, route of administration or after repeated administration. The drug is excreted mainly in the urine (95% on average) and only a small amount in the faeces. The elimination of the drug is prolonged in the case of renal failure.

Hypersensitivity to levetiracetam, other pyrrolidone derivatives or to any of the excipients.

Administration of the preparation to patients with impaired renal function may require appropriate dose adjustment. In patients with severe hepatic impairment, it is recommended that the kidney function be assessed before the appropriate dose is determined. Patients should be monitored for the occurrence of depression and / or suicidal ideation and behavior while taking the drug and appropriate treatment should be considered. The preparation is not suitable for administration to infants and children under 6 years of age. Available data on use in children does not suggest an effect on growth and maturation. However, long-lasting effects on learning, intelligence, growth, endocrine system function, maturation and fertility remain unknown. The safety and efficacy of levetiracetam in infants with epilepsy younger than 1 year of age have not been extensively studied (only 35 infants with partial seizures less than 1 year old received the drug in clinical trials, 13 of them less than 6 months). Table. powl. 750 mg contain sunset yellow orange (E110), which may cause allergic reactions.

Levetiracetam is not recommended during pregnancy and in women of childbearing potential not using contraception unless clearly necessary. There was a reduction in plasma levels of levetiracetam during pregnancy. The reduction in concentration is more pronounced in the third trimester (up to 60% of the value relative to the baseline, before pregnancy). In the case of pregnant women using levetiracetam, appropriate clinical management should be ensured. Discontinuation of antiepileptic therapy may exacerbate the disease, which may be harmful to the mother and the fetus.Levetiracetam is excreted in breast milk - breast-feeding is not recommended. However, if treatment is required during breastfeeding, consider the benefit / risk ratio, taking into account the importance of breastfeeding.

Very common: inflammation of the mucous membranes of the nose and throat, drowsiness, headache. Common: anorexia (risk of anorexia nervosa is greater in the case of combination therapy with topiramate), depression, hostility / aggressiveness, anxiety, insomnia, nervousness, irritability, convulsions, balance disorders, dizziness (central and labyrinth origin), lethargy, tremors, cough , abdominal pain, diarrhea, dyspepsia, vomiting, nausea, rash, asthenia. Uncommon: thrombocytopenia, leukopenia, weight loss or weight gain, suicide attempts, suicidal thoughts, psychotic disorders, behavioral disorders, hallucinations, anger, confusion, emotional instability, agitation, amnesia, impaired memory, ataxia, paresthesia, impaired concentration, double vision, blurred vision, abnormal liver tests, alopecia, eczema, pruritus, muscle weakness, muscle pain, injuries. Rare: infections, pancytopenia, neutropenia, suicide, personality disorders, thinking disorders, choreoathetosis, dyskinesia, hyperkinesia, pancreatitis, hepatic failure, hepatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme. The adverse events profile of levetiracetam is generally similar in adults and children, with the exception of adverse reactions to behavior and mental disorders that were more common in children. In children and adolescents aged 4-16 years, more often than in other age groups or than the general safety profile indicates: very often: vomiting; often: agitation, mood swings, emotional instability, aggression, behavioral disorders and lethargy. In infants and children from 1 month to less than 4 years, irritability (very common) and coordination disorders (common) have been reported more frequently than in other age groups or within the overall safety profile.

Orally.monotherapy. Adults and adolescents from 16 years of age: the recommended starting dose is 250 mg 2 times a day and after 2 weeks of use it can be increased to an initial therapeutic dose of 500 mg 2 times a day. Depending on the clinical response, the daily dose may be further increased every 2 weeks by 250 mg twice daily. The maximum dose is 1500 mg 2 times a day. The efficacy and safety of the drug alone in children and adolescents under 16 years have not been established.Supportive therapy. Adults (≥ 18 years old) and adolescents (from 12 to 17 years) about ≥ 50 kg: the initial therapeutic dose is 500 mg 2 times a day. Administration of this dose can be started on day 1 of treatment. Depending on the clinical response and tolerability, the daily dose can be increased up to 1500 mg 2 times a day. Dosing may be changed by increasing or decreasing the daily dose by 500 mg 2 times a day, every 2-4 weeks.Infants from 6 to 23 months old, children (from 2 to 11 years old) and adolescents (from 12 to 17 years old) about <50 kg: the initial therapeutic dose is 10 mg / kg 2 times a day. Depending on the clinical response and tolerability, the daily dose can be increased up to 30 mg / kg. 2 times a day. Dose adjustments should not exceed the dose reduction or increase by more than 10 mg / kg. 2 times daily, every 2 weeks. The lowest effective dose should be used. In children about the month ≥50 kg dose as for adults. In children about the month 25 kg or less, it is recommended to start treatment with an oral solution (100 mg / ml). The oral solution is recommended for infants and children under 6 years of age.Special groups of patients. Adult and adolescent patients above 50 kg with impaired renal function. Correct function (creatinine clearance - CCr> 80 ml / min / 1.73 m²): 500 -1500 mg twice daily; mild disorder (CCr 50-79 ml / min / 1.73 m²): 500-1000 mg twice daily; moderate functional impairment (CCr 30-49 ml / min / 1.73 m²): 250-750 mg twice daily; severe CCr disorder <30 ml / min / 1.73 m²): 250-500 mg twice daily; end-stage renal failure, patients undergoing dialysis: 500-1000 mg once daily (the first dose of levetiracetam is recommended on the first day of 750 mg, after the dialysis a supplemental dose of 250-500 mg is recommended).Infants, children and adolescents <50 kg with impaired renal function. For doses below 250 mg and patients unable to swallow tablets, an oral solution should be used.Infants and children from 6 to 23 months, children and adolescents <50 kg. Correct function (creatinine clearance - CCr> 80 ml / min / 1.73 m²): 10-30 mg / kg 2 times a day; mild disorder (CCr 50-79 ml / min / 1.73 m²): 10-20 mg / kg 2 times a day; moderate functional impairment (CCr 30-49 ml / min / 1.73 m²): 5-15 mg / kg 2 times a day; severe functional impairment (CCr <30 ml / min / 1.73 m²): 5-10 mg / kg 2 times a day; end-stage renal failure, patients undergoing dialysis: 10-20 mg / kg once a day (on the first day of treatment with levetiracetam a loading dose of 15 mg / kg is recommended, after a dialysis a 5-10 mg / kg supplementary dose is recommended).Infants from 1 to <6 months. Correct function (creatinine clearance - CCr> 80 ml / min / 1.73 m²): 7-21 mg / kg 2 times a day; mild disorder (CCr 50-79 ml / min / 1.73 m²): 7-14 mg / kg 2 times a day; moderate functional impairment (CCr 30-49 ml / min / 1.73 m²): 3.5-10.5 mg / kg 2 times a day; severe CCr disorder <30 ml / min / 1.73 m²): 3.5-7 mg / kg 2 times a day; end-stage renal disease, patients undergoing dialysis: 7-14 mg / kg once a day (on the first day of treatment with levetiracetam a loading dose of 10.5 mg / kg is recommended, after dialysis a supplemental dose of 3.5-7 mg / kg is recommended).Hepatic dysfunction. No dose adjustment is required in patients with mild or moderate hepatic impairment. In patients with severe hepatic impairment, creatinine clearance may not fully reflect the degree of coexisting renal insufficiency. For this reason, it is recommended to reduce the maintenance daily dose by 50% in cases where the creatinine clearance is <60 ml / min / 1.73 m². Way of giving. The tablets should be swallowed with a sufficient amount of liquid, with or without food. The daily dose is given in two equal doses.