Index of drugs

Monotherapy in the treatment of partial onset or partial secondary seizures in patients from 16 years of age with newly diagnosed epilepsy. The drug is indicated as adjunctive therapy: in the treatment of partial onset or partial secondary seizures in adults, children and infants from 1 month of age with epilepsy; in the treatment of myoclonic seizures in adults and adolescents from 12 years of age with juvenile myoclonic epilepsy; in the treatment of primary and generalized tonic-clonic 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. The drug contains sunset yellow.

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 during 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 it is 7 +/- 1 h and does not change depending on the dose, the 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 excipients.

Caution should be used in patients with impaired renal function (dosage modification is necessary). In patients with severe hepatic impairment, it is recommended that the kidney function be assessed before the appropriate dose is determined. When using levetiracetam, patients should be monitored for depression and / or suicidal ideation and behavior and appropriate treatment for these conditions should be considered. Available data on the use of levetiracetam in children do not indicate that the drug affects growth and maturation, but long-term effects on learning, intelligence, growth, endocrine functions, maturation and fertility are not known. The efficacy and safety of levetiracetam alone in children and adolescents <16 years have not been established. The safety and efficacy of levetiracetam in adjunctive therapy in infants aged <1 year have not been carefully studied (only 35 infants <1 year of age received the drug in clinical trials, 13 of them were <6 months of age). The preparation in the form of tablets is not suitable for administration to infants and children aged <6 years. Table. contain an orange yellow that can cause allergic reactions.

Levetiracetam is not recommended during pregnancy and in women of childbearing potential not using contraception unless clearly necessary. Physiological changes occurring during pregnancy can affect the blood concentration of the drug - there was a decrease in levetiracetam concentration during pregnancy, the most 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 can be harmful to both the mother and the fetus. The drug is excreted in human milk - breast-feeding is not recommended. However, if treatment is required during breastfeeding, the importance of the risk-benefit associated with the treatment should be considered, taking into account the importance of breastfeeding.

Very common: drowsiness, asthenia / fatigue. Common: infections, inflammation of the nose and throat, thrombocytopenia, anorexia, weight gain, agitation, depression, emotional instability / mood changes, hostility / aggressiveness, insomnia, nervousness / irritability, personality disorders, thinking disorders, amnesia, ataxia, convulsions, dizziness, headache, hyperkinesia, tremor, balance disorders, concentration disorders, memory disorders, diplopia, blurred vision, worsening of cough, dizziness, abdominal pain, diarrhea, dyspepsia, nausea, vomiting, rash, eczema, pruritus, muscular pain, accidental injuries. Not known: leukopenia, neutropenia, pancytopenia (with bone marrow suppression observed in several cases), weight loss, abnormal behavior, anger, fear, confusion, hallucinations, psychotic disorders, suicide, suicide attempts, suicidal thoughts, paresthesia, inflammation pancreatitis, hepatic failure, hepatitis, abnormal hepatic tests, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme and alopecia. The adverse event profile of levetiracetam is generally similar in adults and children, except for behavioral changes and adverse psychiatric reactions that were more common in children and adolescents than in adults.

Orally.monotherapy. Adults and adolescents from 16 years of ageThe recommended starting dose is 250 mg 2 times daily and should be increased to the initial therapeutic dose of 500 mg twice daily after 2 weeks. 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.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. The oral solution is recommended for use in infants and children aged <6 years.Infants from 1 month to <6 months: oral solution is recommended for use in this age group.Special groups of patients. Adult and adolescent patients > 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 functional impairment (CCr <30 ml / min / 1.73 m²): 250-500 mg twice daily; end-stage renal disease, patients undergoing dialysis: 500-1000 mg once daily (the first day of treatment with levetiracetam is recommended at 750 mg, after the dialysis a supplemental dose of 250-500 mg is recommended).Infants, children and adolescents <50 kg with impaired renal function. 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 / kg2 times a day; moderate functional impairment (CCr 30-49 ml / min / 1.73 m²): 5-15 mg / kg 2 times a day; severe CCr disorder <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. Discontinuation of levetiracetam therapy. If treatment with the preparation is to be discontinued, according to current clinical practice, gradual withdrawal of the preparation is recommended (ie adults and adolescents ≥50 kg: dose reduction by 500 mg twice daily every 2-4 weeks; infants > 6 months, children and adolescents <50 kg: dose reduction should not exceed the reduction of 10 mg / kg twice daily every 2 weeks, infants up to 6 months: dose reduction should not exceed the reduction of 7 mg / kg 2 times a day, every 2 weeks).Way of giving. The daily dose is given in 2 evenly divided doses. The drug can be taken with or without food. For doses <250 mg, patients who are unable to swallow tablets as well as infants and children <6 years should be treated with levetiracetam as an oral solution.