Index of drugs

Monotherapy in the treatment of partial onset or partial secondary seizures in adults and adolescents from 16 years of age with newly diagnosed epilepsy. Adjunctive therapy in the treatment of partial onset or partial seizures in adults, adolescents, 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 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. 1 ml oral solution contains 100 mg levetiracetam.

Antiepileptic drug - a pyrrolidone derivative. The mechanism of action of levetiracetam is still 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. Levetiracetam induces seizure protection in many animal models of partial and primary generalized epileptic seizures, and does not have a seizure effect. The main metabolite is inactive. The anticonvulsant effect in humans, both in epilepsy with partial seizures and generalized seizures, confirmed a wide range of pharmacological action profile of levetiracetam. Following oral administration, levetiracetam is rapidly absorbed from the gastrointestinal tract, reaching a maximum blood concentration of 1.3 hours after administration. 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 metabolic pathway (24% of the dose) is the enzymatic hydrolysis of the acetamide group. 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. In the elderly, the half-life is increased by approximately 40% (10-11 h). After a single dose (20 mg / kg) to children (6-12 years) with epilepsy, the half-life of levetiracetam is 6 hours. After multiple dosing (20-60 mg / kg / day) children with epilepsy (4 -12 years old) levetiracetam was rapidly absorbed. The maximum concentration in blood occurred 0.5-1 h after administration. T_0,5 was about 5 hours. After a single dose (20 mg / kg) of 100 mg / ml oral solution for children with epilepsy (from 1 month to 4 years), levetiracetam was rapidly absorbed and the maximum plasma concentration was observed around 1 h after dosing and the half-life of levetiracetam was 5.3 h.

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

Use with caution in patients with impaired renal function. In patients with severe hepatic impairment, evaluation of renal function is recommended. Patients treated with antiepileptic drugs have reported cases of suicide, suicide attempts and suicidal ideation and behavior; patients should be monitored for depression and / or suicidal ideation and behavior and appropriate treatment should be considered. The preparation in the form of tablets is not suitable for administration to infants and children under the age of 6 years. Available data on use in children does not suggest an effect on growth and maturation, however, long-term effects on learning, intelligence, growth, endocrine functions, maturation and potential effects on fertility remain unknown. Safety and efficacy in infants below the age of 1 have not been thoroughly examined (only 35 infants below the age of 1).received the preparation, 13 of them were aged <6. months of age.). The efficacy and safety of monotherapy in children and adolescents under 16 years have not been established. The solution formulation contains methyl and propyl parahydroxybenzoate, which may cause allergic (delayed) reaction and maltitol - patients with rare hereditary fructose intolerance should not take this form of the drug.

There are no adequate data on the use of the preparation in pregnant women. Pregnancy is not recommended if it is not absolutely necessary. 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, the importance of the risk-benefit associated with the treatment should be considered, taking into account the importance of breastfeeding.

Very common: inflammation of the mucous membranes of the nose and throat; drowsiness, headaches. Common: anorexia; depression, hostility / aggressiveness, anxiety, insomnia, nervousness / irritability; convulsions, balance disorders, dizziness (of central origin), lethargy, tremor; dizziness (labyrinthine origin); cough; abdominal pain, diarrhea, dyspepsia, vomiting, nausea; rash; asthenia / fatigue. Uncommon: thrombocytopenia, leukopenia; weight loss, weight gain; suicide attempts, suicidal thoughts, psychotic disorders, behavioral disorders, hallucinations, anger, confusion, panic attacks, emotional instability / mood swings, agitation; amnesia, impaired memory, impaired coordination of movements / ataxia, paresthesia, attention deficit disorder; double vision, blurred vision; abnormal liver test results; baldness, eczema, pruritus; muscle weakness, muscle pain; injuries. Rare: infections, pancytopenia, neutropenia, suicide, personality disorders, thinking disorders; choreoathetosis, dyskinesia, hyperkinesia; inflammation of the pancreas; liver failure, hepatitis; toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme.

Oral: a daily dose is given in 2 evenly divided doses.Monotherapy: Adults and adolescents from 16 years: the recommended initial dose is 250 mg 2 times a day and after 2 weeks of use should be increased to the initial therapeutic dose of 500 mg 2 times a day. Depending on the clinical response and tolerability, the daily dose may be increased every 2 weeks by 250 mg 2 times a day to a maximum of 1500 mg 2 times a day.Adjunctive therapy: Adults and adolescents (aged 12-17 years) about 50 kg or more: the initial dose is 500 mg 2 times a day (this dose can be started on the first day 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 and children aged 6 to 23 months, children (2-11 years) and adolescents (aged 12-17 years) about the month less than 50 kgThe starting 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. Dosage adjustments should not exceed the dose reduction or increase by 10 mg / kg. 2 times a day every 2 weeks. The lowest effective dose should be used. In children about the month 20 kg or less it is recommended to start treatment with an oral solution. Dosage in children about the month of 50 kg or more is the same as in adults.Oral solution - infants from 1 month to less than 6 months of age: initial dose 7 mg / kg 2 times a day. Depending on the clinical response and tolerability, the daily dose can be increased to 21 mg / kg. 2 times a day. Dose adjustments should not exceed a dose reduction or increase of 7 mg / kg. 2 times daily, every 2 weeks. The lowest effective dose should be used. Treatment of infants should be started with 100 mg / ml oral solution.
In patients with impaired renal function, the daily dose is determined individually depending on the creatinine clearance: clearance> 80 ml / min / 1.73 mm² - 500-1500 mg twice daily; clearance 50-79 ml / min / 1.73 m² - 500-1000 mg twice daily; clearance 30-49 ml / min / 1.73 m² 250-750 mg twice daily; clearance <30 ml / min / 1.73 m² - 250-500 mg twice daily; end-stage renal failure and dialysis patients - 500-1000 mg once daily (the recommended starting dose is 750 mg on the first day of treatment, after the dialysis a supplemental dose of 250-500 mg is recommended). Dose adjustment in infants from 1 to less than 6 months with impaired renal function: clearance> 80 ml / min / 1.73 mm² - 7-21 mg / kg 2 times a day; clearance 50-79 ml / min / 1.73 m² - 7-14 mg / kg 2 times a day; clearance 30-49 ml / min / 1.73 m² - 3.5-10.5 mg / kg 2 times a day; clearance <30 ml / min / 1.73 m² - 3.5-7 mg / kg 2 times a day; end-stage renal disease and dialysis patients - 7-14 mg / kg once a day (on the first day of treatment a loading dose of 10.5 mg / kg is recommended, a follow-up dose of 3.5-7 mg / kg is recommended after dialysis). Adjustment of the dosage in infants and children from 6 to 23 months, children and adolescents less than 50 kg with impaired renal function: clearance> 80 ml / min / 1.73 mm² - 10-30 mg / kg 2 times a day; clearance 50-79 ml / min / 1.73 m² - 10-20 mg / kg 2 times a day; clearance 30-49 ml / min / 1.73 m² 5-15 mg / kg 2 times a day; clearance <30 ml / min / 1.73 m² - 5-10 mg / kg 2 times a day; end-stage renal failure and dialysis patients - 10-20 mg / kg once a day (on the first day of treatment, a loading dose of 15 mg / kg is recommended, after a dialysis a 5-10 mg / kg supplementary dose is recommended). No dose adjustment is required in patients with mild or moderate hepatic impairment; in patients with severe hepatic impairment, it is recommended to assess renal function before choosing the right dose - a 50% reduction in maintenance dose is recommended in cases where the creatinine clearance is <60 ml / min / 1.73 mm².
The preparation should be taken with or without food. The oral solution can be diluted in a glass of water or in a baby bottle.