Keppra tablets p / o 500mg, No. 30

As monotherapy (first choice drug) in the treatment of:
- partial seizures with or without secondary generalization in
adults and adolescents over 16 years of age with newly diagnosed
epilepsy.

As part of complex therapy for treatment:

- partial seizures with or without secondary generalization in
adults and children over 4 years of age with epilepsy;
- myoclonic seizures in adults and adolescents over 12 years old
with juvenile myoclonic epilepsy;
- primary generalized convulsive (tonic-clonic) seizures in
adults and adolescents over 12 years old with idiopathic
generalized epilepsy.

Inside, regardless of the meal.
The daily dose of the drug is divided into two doses in the same dose.
The tablets are taken with a sufficient amount of liquid.

Dosing of the solution is carried out using a measuring syringe with a nominal capacity of 10 ml (corresponds to 1000 mg of levetiracetam) and with a division value of 25 mg (corresponds to 0.25 ml), which is included in the delivery kit of the drug. The measured dose of the drug is diluted in a glass of water (200 ml).

Monotherapy

Adults and adolescents over 16 years of age should begin treatment with a daily dose of 500 mg, divided into 2 doses (250 mg 2 times a day). After 2 weeks, the dose can be increased to the initial therapeutic dose of 1000 mg (500 mg 2 times a day). The maximum daily dose is 3000 mg (1500 mg 2 times a day).

As part of complex therapy

Children over 4 years of age should begin treatment with a daily dose of 20 mg / kg of body weight, divided into 2 doses (10 mg / kg of body weight 2 times a day). Dose changes by 20 mg / kg body weight can be carried out every 2 weeks until the recommended daily dose is reached - 60 mg / kg body weight (30 mg / kg body weight 2 times a day). If the recommended daily dose is intolerant, it may be reduced. The minimum effective dose should be used. The doctor should prescribe the drug in the most appropriate dosage form and dosage, depending on the patient's body weight and the required therapeutic dose. Children weighing 20 kg or less are recommended to start treatment with the drug in the form of an oral solution.

For children weighing more than 50 kg, the dosage is carried out according to the scheme given for adults.

Adults and adolescents over 16 years of age with a body weight of more than 50 kg should begin treatment with a daily dose of 1000 mg, divided into 2 doses (500 mg 2 times a day). Depending on the clinical response and tolerability of the drug, the daily dose can be increased to a maximum of 3000 mg (1500 mg 2 times a day). A dose change of 500 mg 2 times a day can be carried out every 2-4 weeks.

Since levetiracetam is excreted from the body by the kidneys, when prescribing the drug to patients with renal insufficiency and elderly patients Х the dose should be adjusted depending on the creatinine clearance (CC) value.

In children with renal impairment, the dose of levetiracetam should be adjusted according to the degree of renal impairment, using the recommendations given for adults.

Patients with mild to moderate hepatic impairment do not need to adjust the dosage regimen. In patients with decompensated liver function and renal failure, the level of decrease in creatinine clearance may not fully reflect the severity of renal failure. In such cases, with creatinine clearance <70 ml / min, a 50% reduction in the daily dose is recommended.

1 tablet of 500 mg contains:

active substance: levetiracetam - 500 mg;

excipients: croscarmellose sodium, macrogol 6000, silicon dioxide, magnesium stearate; opadry 85F32004 [iron dye yellow oxide (E172), macrogol 3350, partially hydrolyzed polyvinyl alcohol, talc, titanium dioxide (E171)].

- Hypersensitivity to levetiracetam or other
pyrrolidone derivatives , as well as to any components of the drug;
- violation of fructose tolerance (solution);
- children under 4 years of age (safety and effectiveness have not been established).

Carefully

- elderly patients (over 65 years old);
- liver disease in the stage of decompensation;
- renal failure.

Trademarked name: KeppraЃ

International non-proprietary name:

levetiracetam

Dosage forms: oral solution, film-coated tablets.

Composition

1 ml of solution contains:

active substance: levetiracetam - 100 mg;

excipients: sodium citrate, citric acid monohydrate, methyl parahydroxybenzoate, propyl parahydroxybenzoate, ammonium glycyrrhizate, glycerol 85%, maltitol, acesulfame potassium, grape flavor 501040A, purified water.

1 tablet of 250 mg contains:

active substance: levetiracetam - 250 mg;
excipients: croscarmellose sodium, macrogol 6000 ,. Silicon dioxide, magnesium stearate; opadry 85F20694 [indigo carmine dye (E132), macrogol 3350, partially hydrolyzed polyvinyl alcohol, talc, titanium dioxide (EI71)].

1 tablet of 500 mg contains:

active substance: levetiracetam - 500 mg;

excipients: croscarmellose sodium, macrogol 6000, silicon dioxide, magnesium stearate; opadry 85F32004 [iron dye yellow oxide (E172), macrogol 3350, partially hydrolyzed polyvinyl alcohol, talc, titanium dioxide (E171)].

1 tablet of 1000 mg contains:

active substance: levetiracetam - 1000 mg;
excipients: croscarmellose sodium, macrogol 6000, silicon dioxide, magnesium stearate; opadry 85F18422 [macrogol 3350, partially hydrolyzed polyvinyl alcohol, talc, titanium dioxide (E171)].

Description

Solution; transparent almost colorless solution with a characteristic odor.

Tablets 250 mg: blue oval-shaped film-coated tablets with biconvex surfaces, with a one-sided line, on one side of which there is an engraving 'ucb', on the other - '250'; homogeneous at the fracture, white.

Tablets 500 mg: light-yellow oval-shaped film-coated tablets with biconvex surfaces, with a one-sided line, on one side of which there is an engraving 'ucb', on the other - '500'; homogeneous at the fracture, white.

Tablets 1000 mg: white oval-shaped film-coated tablets with biconvex surfaces, with a one-sided line, on one side of which there is an engraving 'ucb', on the other - '1000'; homogeneous at the fracture, white.

Pharmacotherapeutic group:

antiepileptic drug. ATX code: N03AX14.

Pharmacological properties

Pharmacodynamics.
Levetiracetam - the active substance of KeppraЃ - is a derivative of pyrrolidone (S-enantiomer of a-ethyl-2-oxo-1-pyrrolidine-acetamide), differs in chemical structure from known antiepileptic drugs. The mechanism of action of levetiracetam is not fully understood, but it is obvious that it differs from the mechanism of action of known antiepileptic drugs. One of the proposed mechanisms is based on the proven binding to the SV2A synaptic vesicle glycoprotein, which is contained in the gray matter of the brain and spinal cord. It is believed that in this way the anticonvulsant effect is realized, which is expressed in counteracting the hypersynchronization of neural activity. Levetiracetam also acts on GABA receptors and glycine receptors, modulating these receptors through various endogenous agents.Does not alter normal neurotransmission, but suppresses epileptiform neuronal outbursts induced by the GABA agonist bikuculik and the excitation of glutamate receptors. The activity of the drug has been confirmed in relation to both focal and generalized epileptic seizures (epileptiform manifestations / photoparoxysmal reaction).

Pharmacokinetics.
Suction. After oral administration, levetiracetam is well absorbed from the gastrointestinal tract. Absorption occurs completely and is linear, so that the concentration in the blood plasma can be predicted based on the dose of levetiracetam taken, expressed in mg / kg of body weight. The degree of absorption does not depend on the dose and time of food intake. Bioavailability is approximately 100%. The maximum plasma concentration (Stmax) is reached 1.3 hours after oral administration of levetiracetam at a dose of 1000 mg and with a single dose is 31 ?g / ml, after repeated administration (2 times a day) - 43 ?g / ml. The equilibrium state is achieved after 2 days with two doses of the drug.

Pharmacokinetics of levetiracetam in children is linear in the dose range from 20 to 60 mg / kg / day, Cmax is achieved after 0.5-1 hours.

Distribution. The binding of levetiracetam and its main metabolite to plasma proteins is less than 10 %. The volume of distribution (Vd) is approximately 0.5-0.7 l / kg.

Metabolism. The formation of the primary pharmacologically inactive metabolite (ucb L057) occurs without the participation of liver cytochrome P450. Levetiracetam does not affect the enzymatic activity of hepatocytes.

Excretion. The half-life (T1 / 2) from the blood plasma of an adult is 7 + 1 hour and does not depend on the route of administration and dosage regimen. The average total clearance is 0.96 ml / min / kg. 95% of the drug is excreted by the kidneys. The renal clearance of levetiracetam and its metabolite is 0.6 and 4.2 ml / min / kg, respectively.
In elderly patients, T1 / 2 increases by 40% and is 10-11 hours, which is associated with impaired renal function in this category of people.
In patients with impaired renal function, the clearance of levetiracetam and its primary metabolite correlates with creatinine clearance. Therefore, patients with renal insufficiency are advised to select a dose depending on creatinine clearance.
In end-stage renal disease in adult patients, T1 / 2 is 25 hours between dialysis sessions and 3.1 hours during dialysis. During a 4-hour dialysis session, up to 51% of levetiracetam is removed.
In patients with mild to moderate hepatic impairment, significant changes in the clearance of levetiracetam do not occur. In most patients with severely impaired liver function with concomitant renal failure, the clearance of levetiracetam decreases by more than 50%.
T1 / 2 in children after a single oral administration of the drug at a dose of 20 mg / kg body weight is 5-6 hours. The total clearance of levetiracetam in children is about 40% higher than in adults and is in direct proportion to body weight.

Indications for use

As monotherapy (first choice drug) in the treatment of:
- partial seizures with or without secondary generalization in
adults and adolescents over 16 years of age with newly diagnosed
epilepsy.

As part of complex therapy for treatment:

- partial seizures with or without secondary generalization in
adults and children over 4 years of age with epilepsy;
- myoclonic seizures in adults and adolescents over 12 years old
with juvenile myoclonic epilepsy;
- primary generalized convulsive (tonic-clonic) seizures in
adults and adolescents over 12 years old with idiopathic
generalized epilepsy.

- Contraindications

- Hypersensitivity to levetiracetam or other
pyrrolidone derivatives , as well as to any components of the drug;
- violation of fructose tolerance (solution);
- children under 4 years of age (safety and effectiveness have not been established).

Carefully

- elderly patients (over 65 years old);
- liver disease in the stage of decompensation;
- renal failure.

Application during pregnancy and lactation

Adequate and strictly controlled clinical studies on the safety of using levetiracetam in pregnant women have not been conducted, therefore, the drug should not be prescribed during pregnancy, except in cases of extreme necessity.
Physiological changes in a woman's body during pregnancy can affect the plasma concentration of levetiracetam, as well as other antiepileptic drugs. During pregnancy, a decrease in plasma concentration of levetiracetam was noted. This decrease is more pronounced in the first trimester (up to 60% of the baseline concentration in the period before pregnancy). Treatment with levetiracetam in pregnant women should be carried out under special supervision. Interruptions in antiepileptic therapy can worsen the course of the disease, which can harm the health of both the mother and the fetus.
Levetiracetam is excreted in breast milk, therefore, breastfeeding is not recommended for drug treatment.

Method of administration and dosage

Inside, regardless of the meal.
The daily dose of the drug is divided into two doses in the same dose.
The tablets are taken with a sufficient amount of liquid.

Dosing of the solution is carried out using a measuring syringe with a nominal capacity of 10 ml (corresponds to 1000 mg of levetiracetam) and with a division value of 25 mg (corresponds to 0.25 ml), which is included in the delivery kit of the drug. The measured dose of the drug is diluted in a glass of water (200 ml).

Monotherapy

Adults and adolescents over 16 years of age should begin treatment with a daily dose of 500 mg, divided into 2 doses (250 mg 2 times a day). After 2 weeks, the dose can be increased to the initial therapeutic dose of 1000 mg (500 mg 2 times a day). The maximum daily dose is 3000 mg (1500 mg 2 times a day).

As part of complex therapy

Children over 4 years of age should begin treatment with a daily dose of 20 mg / kg of body weight, divided into 2 doses (10 mg / kg of body weight 2 times a day). Dose changes by 20 mg / kg body weight can be carried out every 2 weeks until the recommended daily dose is reached - 60 mg / kg body weight (30 mg / kg body weight 2 times a day). If the recommended daily dose is intolerant, it may be reduced. The minimum effective dose should be used. The doctor should prescribe the drug in the most appropriate dosage form and dosage, depending on the patient's body weight and the required therapeutic dose. Children weighing 20 kg or less are recommended to start treatment with the drug in the form of an oral solution.

For children weighing more than 50 kg, the dosage is carried out according to the scheme given for adults.

Adults and adolescents over 16 years of age with a body weight of more than 50 kg should begin treatment with a daily dose of 1000 mg, divided into 2 doses (500 mg 2 times a day). Depending on the clinical response and tolerability of the drug, the daily dose can be increased to a maximum of 3000 mg (1500 mg 2 times a day). A dose change of 500 mg 2 times a day can be carried out every 2-4 weeks.

Since levetiracetam is excreted from the body by the kidneys, when prescribing the drug to patients with renal insufficiency and elderly patients Х the dose should be adjusted depending on the creatinine clearance (CC) value.

In children with renal impairment, the dose of levetiracetam should be adjusted according to the degree of renal impairment, using the recommendations given for adults.

Patients with mild to moderate hepatic impairment do not need to adjust the dosage regimen. In patients with decompensated liver function and renal failure, the level of decrease in creatinine clearance may not fully reflect the severity of renal failure. In such cases, with creatinine clearance <70 ml / min, a 50% reduction in the daily dose is recommended.

Side effect

Possible side effects are listed below by body system and frequency of occurrence: very often (> 1/10), often (> 1/100, <1/10).

From the nervous system
Very often: drowsiness, asthenic syndrome.

Often: amnesia, ataxia, seizures, dizziness, headache, hyperkinesia, tremor, imbalance, decreased concentration, memory impairment, agitation, depression, emotional lability, mood swings, hostility / aggressiveness, insomnia, nervousness, irritability, personality disorders, violation of thinking.

Individual messages: paresthesias, behavioral disorders, anxiety, restlessness,. confusion, hallucinations, irritability, psychotic disorders, suicide, attempted suicide, and suicidal intentions.

From the side of the organ of vision
Often: diplopia, violation of accommodation.

From the respiratory system
Often: increased cough.

From the digestive system
Often: abdominal pain, diarrhea, dyspepsia, nausea, vomiting, anorexia, weight gain.
Individual messages: pancreatitis, liver failure, hepatitis, changes in liver function tests, weight loss.

On the part of the skin
Often: skin rash, eczema, itching.
Separate messages: alopecia (in some cases, hair restoration was observed after discontinuation of the drug).

Changes in laboratory parameters
Some reports: leukopenia, neutropenia, pancytopenia (in some cases with bone marrow suppression), thrombocytopenia.

Other
Individual messages: infections, nasopharyngitis, myalgia.

Overdose

—имптомы: сонливость, тревожность, агрессивность., угнетение сознани¤, угнетение дыхани¤, кома.

Ћечение: в остром периоде - искусственный вызов рвоты и промывание желудка с последующим назначением активированного угл¤. —пецифического антидота дл¤ леветирацетама нет. ѕри необходимости проводитс¤ симптоматическое лечение в услови¤х стационара с использованием гемодиализа (эффективность диализа дл¤ леветирацетама составл¤ет 60 %, дл¤ его первичного метаболита Ч 74 %).

¬заимодействие с другими лекарственными препаратами

ѕрепарат не взаимодействует с противоэпилептическими препаратами (фенитоин, карбамазепин, вальпроева¤ кислота, фенобарбитал, ламотригин, габапентин и примидон).

Ћеветирацетам в суточной дозе 1000 мг не измен¤ет фармакокинетику пероральных противозачаточных средств (этинилэстрадиола и левоноргестрела).

Ћеветирацетам в суточной дозе 2000 мг не измен¤ет фармакокинетику дигоксина и варфарина.

?игоксин, пероральные противозачаточные средства и варфарин не вли¤ют на фармакокинетику леветирацетама.

ѕри совместном приеме с топираматом выше веро¤тность развити¤ анорексии.

ѕолнота всасывани¤ леветирацетама не измен¤етс¤ под воздействием пищи, при этом скорость всасывани¤ несколько снижаетс¤.

?анных по взаимодействию леветирацетама с алкоголем нет.

ќсобые указани¤

?сли требуетс¤ прекратить прием препарата, то отмену лечени¤ рекомендуетс¤ осуществл¤ть постепенно (уменьша¤ разовую дозу на 500 мг каждые 2-4 недели). ” детей снижение дозы не должно превышать 10 мг/кг массы тела 2 раза сутки каждые 2 недели.
—опутствующие противоэпилептические лекарственные препараты (в период перевода пациентов на прием леветирацетама) желательно отмен¤ть постепенно. »меющиес¤ сведени¤ о применении препарата у детей не свидетельствуют о каком-либо его отрицательном вли¤нии на развитие и половую зрелость. ќднако отдаленные последстви¤ лечени¤ на способность детей к обучению, их интеллектуальное развитие, рост, функции эндокринных желез, половое развитие и фертильность остаютс¤ неизвестными.

ѕациентам с заболевани¤ми почек и декомпенсированными заболевани¤ми печени рекомендуетс¤ исследование функции почек перед началом лечени¤. ѕри нарушении функции почек может потребоватьс¤ коррекци¤ дозы. ¬ св¤зи с имеющимис¤ сообщени¤ми о случа¤х суицида, суицидальных намерений и попыток суицида при лечении леветирацетамом следует предупреждать пациентов о необходимости немедленно сообщать лечащему врачу о по¤влении любых симптомов депрессии или суицидальных намерений.

–аствор дл¤ приема внутрь содержит мальтитол, поэтому пациентам с нарушением толерантности к фруктозе прием препарата  еппраЃ в соответствующей лекарственной форме противопоказан.

¬ли¤ние на способность к вождению автотранспорта и управлению механизмами ¬ли¤ние препарата  еппра на способность к вождению автотранспорта и управлению механизмами специально не изучалось. “ем не менее, в силу различной индивидуальной чувствительности к препарату со стороны центральной нервной системы в период лечени¤ необходимо воздерживатьс¤ от вождени¤ автотранспорта и зан¤тий потенциально опасными видами де¤тельности, требующими повышенной концентрации внимани¤ и быстроты психомоторных реакций.

‘ормы выпуска

–аствор дл¤ приема внутрь 100 мг/мл. ѕо 300 мл раствора во флаконах темного стекла (тип III, ?вр. ‘.) с навинчивающейс¤ крышкой из белого полипропилена с Ђзащитой от детейї. ѕо 1 флакону в комплекте с мерным шприцем (полиэтилен / полистирол) вместе с инструкцией по применению в картонной пачке. “аблетки покрытые пленочной оболочкой 250 мг, 500 мг, 1000 мг. ѕо 10 таблеток в контурной ¤чейковой упаковке (блистере) [ѕ¬’ / фольга алюминиева¤]. ѕо 3 или 6 блистеров вместе с инструкцией по применению в картонной пачке.

”слови¤ хранени¤

–аствор: при температуре не выше 30 ?—, в защищенном от света месте.
“аблетки: при температуре не выше 25 ?—, в сухом месте.

’ранить в недоступном дл¤ детей месте!

—рок годности

Solution: 2 years. Use an open bottle within two months.

Tablets: 3 years.
Do not use after the expiration date.

Terms of dispensing from pharmacies
Prescription.