Kepayra-vero - instructions for use, dose, side effects, contraindications

	250 mg	500 mg	750 mg	1000 mg
Active substance:
Levetiracetam	250 mg	500 mg	750 mg	1000 mg
Auxiliary substances for the preparation of the core tablet:
	324.5 mg	650.0 mg	973.5 mg	1300 mg
[Corn starch	58.0 mg	116.0 mg	174.0 mg	232.0 mg
Povidone (polyvinylpyrrolidone)	7.0 mg	15.0 mg	21,0 mg	30.0 mg
Silica colloidal dioxide (aerosil)	4.0 mg	8,0 mg	12,0 mg	16.0 mg
Talc	5.0 mg	10,0 mg	15.0 mg	20.0 mg
Magnesium stearate]	0.5 mg	1,0 mg	1.5 mg	2.0 mg
Auxiliary substances for the preparation of a tablet coated with a film coating, with a mass of:
	334.5 mg	670.0 mg	1003.5 mg	1340 mg
Opaprai II gray or yellow, or orange, or white	10.0 mg	20.0 mg	30.0 mg	40.0 mg
[Hypromellose (hydroxypropylmethylcellulose)	28,0%	28,0%	28,0%	28,0%
Lactose Monohydrate	36,0%	36,0%	36,0%	36,0%
Macrogol (polyethylene glycol 4000)	10,0%	10,0%	10,0%	10,0%
For Opadrai II gray dyes:
Titanium dioxide	24,94%
Iron oxide black	0,250%
Iron oxide yellow	0,250%
Aluminum lacquer based on indigo carmine dye	0,560%
For Opadrai II yellow dyes:
Titanium dioxide		22,87%
Iron oxide red		0,04%
Aluminum lacquer based on quinoline yellow dye		3,090%
For Opadrai II orange dyes:
Titanium dioxide			8,4%
Iron oxide yellow			1,15%
Aluminum lacquer based on the sunset yellow dye			16,4%
Aluminum lacquer based on indigo carmine dye			0,05%
For Opadrai II white dyes:
Titanium dioxide]				26,0%

Description:

Tablets coated with a film coat of gray color (for a dosage of 250 mg), yellow (for a dosage of 500 mg), orange (for a dosage of 750 mg) and white (for dosage 1000 mg), oblong, biconvex with a risk.

Pharmacotherapeutic group:Antiepileptic remedy

ATX: & nbsp

N.03.A.X Other antiepileptic drugs

N.03.A.X.14 Levetiracetam

Pharmacodynamics:

The active substance of the drug, levetiracetam, is a pyrrolidone derivative (S-enantiomer α-ethyl-2-oxo-1-pyrrolidineacetamide) differs in chemical structure from other anticonvulsants.

Mechanism of action

The mechanism of action of levetiracetam is not fully understood, but it differs from the mechanism of action of other anticonvulsants. In experiments in vitro and in vivo shown, that levetiracetam does not affect the basic properties of the cell and normal nervous transmission.

In studies in vitro It is shown that, partially reducing the calcium currents Ntype and reducing the release of calcium ions from the intracellular depot of neurons, levetiracetam changes the concentration of calcium ions inside neurons.In addition, it partially eliminates the decrease in the currents of GABA and glycine channels caused by zinc and β-carbolines. Moreover, in studies in vitro shown, that levetiracetam binds to specific areas of the rat brain. This site is a 2A synaptic vesicle protein, which is supposed to be involved in the fusion of vesicles and exocytosis of neurotransmitters. Levetiracetam and its analogues binding to the protein 2A of synaptic vesicles exhibit anticonvulsant activity in the audiogenic model of epilepsy in mice, and the stronger the bond, the higher the activity. These data imply that the binding of levetiracetam to the 2A protein of synaptic vesicles causes its anticonvulsant action.

Pharmacodynamic effects

Levetiracetam has an anticonvulsant effect on many models of partial and primarily generalized seizures in animals without concomitant pro-cramping effect. The main metabolite of levetiracetam is inactive.

Levetiracetam exhibits anticonvulsant activity in partial and generalized epilepsy in humans (epileptiform discharge / photoprooksizmalny response), which confirms its wide range of pharmacological effects.

Pharmacokinetics:

Levetiracetam is a well-soluble and permeable compound. The pharmacokinetic profile is linear in nature with low intra- and interindividual variability. After a long period of application, there is no change in the clearance. There is no evidence of sexual, racial or diurnal differences. The pharmacokinetic properties of levetiracetam in patients with epilepsy and healthy volunteers are comparable.

Due to complete and linear absorption, the plasma concentration is predictable based on the dose of levetiracetam expressed in mg / kg of body weight. Therefore, it is not necessary to monitor the plasma concentration of levetiracetam.

Adults and children show a high correlation between the concentration of levetiracetam in plasma and saliva (saliva / plasma ratios range from 1-1.7 for oral tablets and for oral administration 4 hours after ingestion).

Adults and teenagers

Absorption

After oral administration levetiracetam quickly absorbed. Absolute bioavailability after oral administration is close to 100%.

The maximum concentration in plasma (C_mOh) is achieved after 1.3 hours.The equilibrium state is achieved two days after taking the drug twice a day.

FROM_mOh usually is 31 and 43 μg / ml after a single dose 1000 mg and reception 1000 mg of the drug twice a day.

The degree of absorption does not depend on the dose and on the intake of food.

Distribution

There is no data on the distribution in humans.

Levetiracetam and its main metabolite weakly bind to plasma proteins (<10%). The volume of distribution of levetiracetam is about 0.5-0.7 l / kg, which roughly corresponds to the volume of water in the body.

Biotransformation

Levetiracetam is poorly metabolized in the human body. The main metabolic pathway (24% dose) is the enzymatic hydrolysis of the acetamide group. Isozymes of liver cytochrome P450 do not participate in the formation of the main metabolite (ucb L057). Hydrolysis of the acetamide group occurs in many tissues, including blood cells. Metabolite ucb L057 is pharmacologically inactive.

Two secondary metabolites were also detected. The former is formed by hydroxylation of the pyrrolidone ring (1,6% of the dose), the second - by opening the pyrrolidone ring (0.9% dose).

Other unidentified metabolites are only 0.6% of the dose.

Optical isomerization of levetiracetam and its main metabolite in vivo not detected.

Levetiracetam and its main metabolite do not inhibit the main isoenzymes of cytochrome P450 of the human liver (CYP3A4, 2A6, 2C9, 2C19, 2D6, 2E1 and 1A2), glucuronyl transferase (UGT1A1 and UGT1A6) and epoxy hydroxylase in vitro.

Levetiracetam also does not affect the glucuronation of valproic acid in vitro.

In human hepatocyte culture levetiracetam had little or no effect on the activity of isoenzymes CYP1A2, SULT1E1 and UGT1A1. Levetiracetam weakly induced isoenzyme activity CYP2B6 and CYP3A4. Data on in vitro and data on drug interaction with oral contraceptives, digoxin and warfarin in vivo show that significant induction of enzymes in vivo not expected. Therefore, the interaction of levetiracetam with other substances is unlikely.

Excretion

The half-life in adults is 7±1 rank depends on the dose, route of administration or duration of administration. The average overall clearance is 0.96 ml / min / kg. The main way of elimination is excretion in the urine (about 95% of the dose, of which 93% output within 48 hours).Excretion with faeces is only 0.3% dose.

The total excretion of levetiracetam and its main metabolite is correspondingly 66 and 24% of the dose taken within the first 48 hours. The renal clearance of levetiracetam and ucb L057 is 0.6 and 4.2 ml / min / kg, respectively, which indicates the excretion of levetiracetam by glomerular filtration followed by tubular reabsorption, and the main metabolite - along with glomerular filtration - by active tubular secretion.

Elimination of levetiracetam correlates with creatinine clearance.

Elderly

The half-life in the elderly increases by 40% (up to 10-11 h), which is due to a decrease in kidney function in this population (see section "Method of administration and dose").

Renal insufficiency

The apparent clearance of levetiracetam and its main metabolite depends on the creatinine clearance. In this regard, in patients with moderate renal insufficiency and severe renal failure, it is recommended to adjust the maintenance dose of the drug depending on the creatinine clearance (see the section "Dosing and Administration").

In adult patients with terminal renal insufficiency, the half-life is 25 h between hemodialysis sessions and 3.1 h during the procedure.

During a typical 4-hour hemodialysis session, approximately 51% levetiracetam.

Impaired liver function

In patients with mild and moderate hepatic insufficiency, the clearance of levetiracetam varies only slightly. In the majority of patients with severe hepatic insufficiency, the clearance of levetiracetam decreases by more than 50%, which is due to concomitant renal failure (see section "Method of administration and dose").

Children under 12 years of age

Children aged 4-12 years

After a single dose at a dose of 20 mg / kg, the elimination half-life of children 6-12 years of age is 6 h. The body weight corrected apparent apparent clearance is 30% higher than that in adults with epilepsy.

After prolonged use of the drug at a dose of 20-60 mg / kg / day, absorption of levetiracetam in children 4-12 years of age is rapid. FROM_mOh is achieved within 0.5-1 h. With_mOh and the area under the "concentration-time" curve is linear and proportional to the dose. The terminal elimination half-life is 5 hours.The apparent clearance is 1.1 ml / min / kg.

Children aged 1 month to 4 years

After a single administration of the drug in the form of a solution for oral administration with a dosage 100 mg / ml in a dose 20 mg / kg levetiracetam in children with epilepsy at the age of 1 months to 4 years is quickly absorbed, C_mOh in plasma is achieved through 1 h. Results of pharmacokinetic studies indicate that the half-life in this category of patients is shorter (5.3 h) than in adults (7.2 h), and the apparent clearance is higher (1.5 ml / min / kg) than in adults (0.96 ml / min / kg).

In the population pharmacokinetic analysis performed in patients aged from 1 months to 16 years, the apparent volume of distribution and apparent clearance strongly depended on the body weight (the latter increased with increasing body weight). Age also has an effect on both parameters. This effect is most pronounced in young children and gradually decreases as it grows up, completely disappearing at the age of 4 years.

In both analyzes of population pharmacokinetics, the apparent clearance of levetiracetam was increased by 20% if it was used with anticonvulsants, which cause the induction of microsomal liver enzymes.

Indications:

Levetiracetam is indicated as a monotherapy for the treatment of partial seizures with or without secondary generalization in patients older than 16 years with a newly diagnosed epilepsy.

As an auxiliary therapy levetiracetam is indicated for treatment:

- partial seizures with secondary generalization or without it in patients with epilepsy with 6 years.

- myoclonic seizures in patients with juvenile myoclonic epilepsy with 12 years.

- primary-generalized tonic-clonic seizures in patients with idiopathic generalized epilepsy with 12 years.

Contraindications:

Hypersensitivity to levetiracetam or pyrrolidone derivatives, other components of the drug.

Children age up to 6 years.

Patients with rare hereditary disorders, such as galactose intolerance, lactase deficiency in lobes, or glucose-galactose malabsorption, should not be taken.

Pregnancy and lactation:

Pregnancy

In the post-registration data of several prospective pregnancy registers, the outcomes in more than 1000 women who received monotherapy with levetiracetam in the first trimester of pregnancy.These data, in general, do not indicate a significant increase in the risk of gross congenital anomalies, however, teratogenic risk is not completely excluded. In comparison with monotherapy, therapy with several anticonvulsant drugs is associated with an increased risk of congenital anomalies, and therefore monotherapy is recommended. Animal studies indicate reproductive toxicity.

In the absence of strong reasons levetiracetam should not be used during pregnancy, as well as in women with childbearing potential, who do not use reliable methods of contraception.

Like other anticonvulsant drugs, physiological changes during pregnancy can affect the concentration of levetiracetam. During pregnancy, there is a decrease in the plasma concentration of levetiracetam. This decline is most pronounced during the third trimester (up to 60% of the baseline concentration observed before pregnancy). For pregnant women receiving levetiracetam, proper monitoring should be established. Cancellation of anticonvulsant therapy can lead to an exacerbation of the disease,which can negatively affect the condition of the mother and fetus.

Breastfeeding period

Levetiracetam penetrates into breast milk. Breastfeeding during the drug is not recommended.

However, if levetiracetam therapy should be continued during breastfeeding, the expected benefit and the potential risk of treatment and the importance of breastfeeding should be correlated.

Fertility

In animal studies, no effect on fertility was detected. Clinical data are not available, the potential risk to humans is unknown.

Dosing and Administration:

Dosing regimen

Monotherapy in adults and adolescents with 16 years

The recommended initial dose is 250 mg twice daily, which must be increased two weeks before the initial therapeutic 500 mg twice daily. The dose may be increased in increments of 250 mg twice a day every two weeks, depending on the clinical response. The maximum dose is 1500 mg twice a day.

Auxiliary therapy in adults (18 years and older) and adolescents (12-17 years) with a body weight of 50 kg and more

The initial therapeutic dose is 500 mg twice a day. This dose can be used from the first day of treatment.

Depending on the clinical response and tolerability, the daily dose can be raised to 1500 mg twice a day. The dose may be increased or decreased by 500 mg twice a day every 2-4 weeks.

Special patient groups

Elderly (65 years and over)

In elderly patients with impaired renal function, dose adjustment is necessary (see "Renal failure" below).

Renal insufficiency

Depending on the degree of impaired renal function, the daily dose is selected individually. To use the dose adjustment table, it is necessary to calculate the clearance of creatinine (CK) of the patient in ml / min.

CK in ml / min can be determined using the serum creatinine concentration (mg / dL) according to the following formula (for adults and adolescents with a body weight of 50 kg or more):

CK (ml / min) = [(140 - age, years) х body weight, kg / 72 x creatinine concentration in plasma, mg / dL] x (0.85 for women)

Then, correction for the body surface area (TFT) is introduced as follows:

KK (ml / min / 1.73 m²) = [KK, ml / min / PPT of the patient, m²] x 1.73

Correction of the dose in adults and adolescents with impaired renal function, body weight of which exceeds 50 kg:

Group	Creatinine clearance (ml / min / 1.73 m²)	Dose and frequency of admission
Norm	>80	500-1500 mg 2 times a day
Lightweight	50-79	500-1000 mg twice daily
Medium	30-49	250-750 mg 2 times a day
Heavy	<30	250-500 mg 2 times a day
Terminal stage of renal failure - patients on hemodialysis ⁽¹⁾		500-1000 mg once a day ⁽²⁾

⁽¹⁾ On the first day, a loading dose of 750 mg is recommended.

⁽²⁾ Upon completion of hemodialysis, an additional dose of 250-500 mg is recommended.

Due to the fact that the clearance of levetiracetam depends on the function of the kidneys, children with renal insufficiency are selected for its dose depending on the QC. These guidelines are based on studies in adult patients.

KK in ml / min / 1.73 m² in children and adolescents can be estimated from the plasma concentration of creatinine (in mg / dL) according to the following formula (Schwarz formula):

KK (ml / min / 1.73 m²) = height (cm) x ks/ plasma creatinine concentration (mg / dL),

Where ks= 0.45 for children under 1 year; 0.55 for children aged 1-13 years and females; 0,7 - adolescent male.

Correction of dose in children and adolescents with impaired renal function, body weight of less than 50 kg:

Group	KK (ml / min / 1.73 m²)	Dose and frequency of admission
Group	KK (ml / min / 1.73 m²)	1-6 months	From 6 months
Norm	>80	7-21 mg / kg (0.07-0.21 ml / kg) 2 times per day	10-30 mg / kg (0.1-0.3 ml / kg) 2 times per day
Lightweight	50-79	7-14 mg / kg (0.07-0.14 ml / kg) 2 times per day	10-20 mg / kg (0,1-0,2 ml / kg) 2 times per day
Medium	30-49	3,5-10 mg / kg (0.035-0.105 ml / kg) 2 times per day	5-15 mg / kg (0.05-0.15 ml / kg) 2 times a day
Heavy	<30	3,5-7 mg / kg (0.035-0.07 ml / kg) 2 times per day	5-10 mg / kg (0.05-0.1 ml / kg) 2 times per day
Terminal stage of renal failure - patients on hemodialysis ⁽¹⁾		7-14 mg / kg (0.07-0.14 ml / kg) 1 once a day^{(2) (4)}	10-20 mg / kg (0,1-0,2 ml / kg) 1 once a day^{(3) (5)}

⁽¹⁾ At doses less than 250 mg, and in patients not able to swallow the tablets, an oral solution is used.

⁽²⁾ On the first day, a loading dose of 10.5 mg / kg (0.105 ml / kg) is recommended.

⁽³⁾ On the first day, a loading dose of 15 mg / kg (0.15 ml / kg) is recommended.

⁽⁴⁾ After completion of hemodialysis, an additional dose of 3.5-7 mg / kg (0.035-0.07 ml / kg) is recommended.

⁽⁵⁾ After completion of hemodialysis, an additional dose of 5-10 mg / kg (0.05-0.1 ml / kg) is recommended.

Impaired liver function

In patients with mild to moderate hepatic insufficiency, dose adjustment is not required. In patients with severe hepatic insufficiency, the value of QA can be misleading about the degree of renal failure.

Therefore, for KK <60 ml / min / 1.73 m² should reduce the maintenance dose of the drug by 50%.

Children

The drug is prescribed in the most convenient dosage form and dosage depending on the age, body weight and the required dose.

Tablets are not intended for use in children younger than 6 years. In such patients, the drug should be administered in a dosage form for oral administration. In addition, the available dosages of the tablets are not intended for initial dose selection in children weighing less than 25 kg, patients who are unable to swallow tablets, and also if necessary, less than 250 mg. In all these cases, it is recommended to use the solution for oral administration.

Monotherapy

The efficacy and safety of levetiracetam in children and adolescents under 16 years of age has not been established as monotherapy.

No data available.

Auxiliary therapy in children 6-23 months, 2-11 years and adolescents (12-17 years) with body weight less than 50 kg

Children younger than 6 years it is recommended to use a solution for oral administration. The initial dose is 10 mg / kg 2 times a day.

Depending on the clinical response and tolerability, the dose may be increased to 30 mg / kg 2 times a day. The dose may be increased or decreased in steps of 10 mg / kg twice a day every two weeks. It is necessary to apply the lowest effective dose.The dosage regimen in children with a body weight of 50 kg or more is not different from adults.

Recommended doses in children older than 6 months:

Body mass	Initial dose: 10 mg / kg 2 times a day	Maximum dose: 30 mg / kg 2 times a day
6 kg⁽¹⁾	60 mg (0,6 ml) 2 times per day	180 mg (1,8 ml) 2 times per day
10 kg⁽¹⁾	100 mg (1 ml) 2 times per day	300 mg (3 ml) twice daily
15 kg⁽¹⁾	150 mg (1.5 ml) twice daily	450 mg (4.5 ml) twice daily
20 kg⁽¹⁾	200 mg (2 ml) 2 times per day	600 mg (6 ml) 2 times per day
25 kg⁽¹⁾	250 mg twice daily	750 mg twice a day
From 50 kg⁽²⁾	500 mg twice a day	1500 mg 2 times per day

⁽¹⁾ Children with a body weight of 25 kg or less are recommended to prescribe the drug in the dosage form solution for ingestion, 100 mg / ml

⁽²⁾ The dosage regimen in children with a body weight of 50 kg or more is not different from adults.

Auxiliary therapy in children aged 1-6 months

The drug is used in the dosage form "oral solution".

Mode of application

Inside, squeezed enough water, regardless of food intake. The daily dose is divided into two equal doses.

Side effects:

Summary of security profile

The adverse events profile presented below is based on an analysis of pooled placebo-controlled clinical studies of levetiracetam for all indications (total number of patients is 3416).These data are supplemented by data on the use of levetiracetam in the context of open extended clinical trials, as well as post-registration data. The most frequently reported adverse reactions were nasopharyngitis, drowsiness, headache, weakness and dizziness. The safety profile of levetiracetam generally does not differ depending on age (in adults and children) and approved indications for use (variants of epilepsy).

Table data on adverse reactions

Undesirable reactions identified in clinical trials and post-registration monitoring (in adults, adolescents and children older than 1 th month) are presented in the table for system-organ classes and frequency. Frequency grading: very often (≥1/10), often (≥1/100 and <1/10), infrequently (≥1/1000 and <1/100), rarely (≥1/10 000 and <1/1000) and very rarely (<1/10 000).

System-Organ Class MedDRA	Frequency Category
System-Organ Class MedDRA	Often	Often	Infrequently	Rarely
Infections and invasions	Nasopharyngitis			Infections
On the part of the blood and lymphatic system			Thrombocytopenia, leukopenia	Pancytopenia, neutropenia, agranulocytosis
From the immune system				Drug reaction with eosinophilia and systemic manifestations (DRESS)
Metabolic and nutritional disorders		Anorexia	Decrease or increase in body weight	Hyponatremia
Mental violations		Depression, hostility/ aggression, insomnia, nervousness/ irritability	Suicidal attempts, suicidal thoughts, psychotic disorders, behavioral disorders, hallucinations, anger, confusion, emotional lability / changes mood, agitation	The suicide, disorder personality, violation of thinking
From the nervous system	Drowsiness, headache	Convulsions, imbalance, dizziness, lethargy, tremor	Amnesia, memory impairment, movement coordination disorder or ataxia, paresthesia, attention disorder	Choreoathetosis, dyskinesia, hyperkinesia
From the side of the organ of vision			Diplopia, impaired vision
From the side of the organ of hearing and balance		Vertigo
On the part of the respiratory system, the organs of the thorax and the mediastinum		Cough
From the gastrointestinal tract		Abdominal pain, diarrhea, indigestion, vomiting, nausea		Pancreatitis
From the liver and biliary tract			Violation functional liver tests	Hepatic insufficiency, hepatitis
From the skin and subcutaneous tissues		Rash	Alopecia, eczema, itching	Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme
From the musculoskeletal and connective tissues			Muscle weakness, myalgia
Are common disorders and disorders at the site of administration		Asthenia/ fatigue
Injuries, poisoning and complications procedures			Injury

Description of individual adverse reactions

With the simultaneous use of topiramate and levetiracetam, the risk of anorexia increases.

In some cases, alopecia has been reversed after the removal of levetiracetam.

In some patients with pancytopenia, bone marrow depression was detected.

Children

Within the placebo-controlled and open extended trials of levetiracetam, 190 patients aged 1 month to 4 years were treated, 60 of whom received levetiracetam in placebo-controlled trials. Within the framework of placebo-controlled and open-ended extended trials, 645 patients aged 4-16 years were treated, 233 of whom received levetiracetam in placebo-controlled trials.For both age ranges, data are also available on the post-registration experience of levetiracetam.

The profile of adverse events of levetiracetam, in general, does not differ depending on age (in adults and children), and also does not depend on approved indications for use (variants of epilepsy). With the exception of behavioral and psychiatric adverse reactions that occurred more frequently in children than in adults, in placebo-controlled studies, the safety profile of levetiracetam in children was comparable to that of adults. In children aged 4-16 years, vomiting (very often, 11.2%), agitation (often, 3.4%), mood changes (often, 2.1%), emotional lability (often, 1.7%) , aggression (often, 8.2%), behavioral disorders (often 5.6%) and lethargy (often, 3.9%) were more frequent than in other age groups and general safety profile. In children aged 1 month to 4 years, irritability (very often 11.7%) and impaired coordination of movements (often, 3.3%) were noted more often than in other age groups and the general safety profile.

Cognitive and neuropsychological effects of levetiracetam in children aged 4-16 with partial seizures were evaluated in double-blind,placebo-controlled studies of the safety profile using design of no less safety. It was shown that levetiracetam is not different (no less safe) from placebo on changes from the initial values on the "Attention and Memory Leiter-R" scale (Leiter-R Attention and Memory), the scale "Integrated Monitoring of Memory" (Memory Screen Composite) in patients who underwent "protocol analysis". The results of a study of behavioral and emotional functions confirming that aggressive behavior develops against the background of the use of levetiracetam are obtained using a standardized method using a validated instrument - the Achenbach's Children's Behavior QuestionnaireAchenbach Child Behavior Checklist). However, in patients who took levetiracetam long-term in the framework of open studies, there were no violations of behavioral and emotional functions, in particular, the level of aggressive behavior did not differ from the initial one.

Reporting suspected adverse reactions

After the state registration of the drug it is very important to report its suspected adverse reactions. Medical workers are advised to report any suspected adverse reactions to Roszdravnadzor.

Overdose:

Symptoms

In case of an overdose of levetiracetam, drowsiness, agitation, aggression, oppression of consciousness, respiratory depression and coma were noted.

Treatment

After an acute overdose, wash the stomach or induce vomiting. The antidote of levetiracetam was not found. Treatment is symptomatic, may include the use of hemodialysis. Dialyzing activity against levetiracetam is 60%, with respect to the main metabolite - 74%.

Interaction:

Anticonvulsants

According to pre-registration clinical studies levetiracetam does not affect the serum concentrations of other anticonvulsant drugs: phenytoin, carbamazepine, valproic acid, phenobarbital, lamotrigine, gabapentin and primidone - and these anticonvulsant drugs do not affect the pharmacokinetics of levetiracetam.

Similar to adults, in children at doses up to 60 mg / kg / day levetiracetam does not interact with other medications.

A retrospective assessment of pharmacokinetic interactions in children and adolescents with epilepsy (4-17 years) confirms that levetiracetam as an auxiliary therapy does not affect the equilibrium serum concentrations of simultaneously used carbamazepine and valproic acid. However, there is evidence that the clearance of levetiracetam in children taking anticonvulsant drugs - inducers of microsomal liver enzymes - is increased by 20%. Correction of the dose is not required.

Probenecid

Probenecid (500 mg 4 times a day) is a blocker of tubular secretion in the kidneys, it is shown that it inhibits renal clearance of the main metabolite, but not levetiracetam. Nevertheless, the concentration of the main metabolite remains low. It is expected that other drugs excreted through active tubular secretion can reduce renal clearance of the main metabolite. The effect of levetiracetam on probenecid has not been studied; the effect of levetiracetam on other drugs excreted by active tubular secretion, including non-steroidal anti-inflammatory drugs, sulfonamides and methotrexate, it is not known.

Oral contraceptives and other pharmacokinetic interactions

Levetiracetam at a dose of 1000 mg per day had no effect on the pharmacokinetics of oral contraceptives (ethinyl estradiol and levonorgestrel); The hormonal status (the content of luteinizing hormone and progesterone) did not change. Levetiracetam in a dose 2000 mg per day had no effect on the pharmacokinetics of digoxin and warfarin, prothrombin time did not change. The simultaneous use of digoxin, oral contraceptives and warfarin did not affect the pharmacokinetics of levetiracetam.

Antacids

Data on the effect of antacids on the absorption of levetiracetam are absent.

Laxatives

There are isolated reports of a decrease in the efficacy of levetiracetam when taken together with an osmotic laxative macrogol. Concerning macrogol Do not take one hour before and after taking levetiracetam.

Food and alcohol

Food does not affect the degree of absorption of levetiracetam, but somewhat reduces its rate. Data on the interaction of levetiracetam with ethanol are absent.

Special instructions:

Abolition of therapy

It is recommended to cancel the drug gradually.For example, in adults and adolescents with a body weight of more than 50 kg, dose reduction should be carried out at a step of 500 mg 2 times a day no more often than every 2-4 weeks; in children older than 6 months with a body weight of less than 50 kg, dose reduction should be carried out in steps of not more than 10 mg / kg 2 times a day no more often than every two weeks; in children younger 6 months, the dose reduction should be carried out in increments of no more than 7 mg / kg 2 times a day no more often than every two weeks.

Renal insufficiency

The use of levetiracetam in patients with renal insufficiency may require dose adjustment. In patients with severe hepatic insufficiency, it is recommended to evaluate the function of the kidneys before starting the dose selection (see the section "Dosage and Administration").

Suicide

In patients taking anticonvulsants (including levetiracetam), there was suicide, suicide attempts, suicidal thoughts and behavior. A meta-analysis of randomized, placebo-controlled trials of anticonvulsant drugs showed a slight increase in the risk of suicidal thoughts and behavior. The mechanism of its implementation is not known.

In connection with the foregoing, it is necessary to monitor patients with symptoms of depression or suicidal thoughts and behavior and prescribe appropriate therapy.Patients (and carers) should be informed of the need to seek medical help if they develop symptoms of depression and / or suicidal thoughts and behavior.

Children

Tablets are not intended for use in children younger than 6 years.

According to available data levetiracetam does not affect growth and puberty. However, the long-term impact on learning, intelligence, growth, endocrine function, puberty and child fertility is not known.

The efficacy and safety of levetiracetam as an anticonvulsant in children younger than one year with epilepsy has not been adequately studied. In clinical trials, the drug was administered to only 35 infants under one year of age with partial seizures, of which only 13 were less 6 months.

Effect on the ability to drive transp. cf. and fur:

Studies on the impact on the ability to drive vehicles and work with mechanisms have not been conducted.

Due to individual differences in susceptibility, some patients may experience drowsiness and other disorders from the central nervous system, especially at the beginning of therapy and after increasing the dose.Therefore, it is recommended to use caution when driving vehicles and working with mechanisms. If these symptoms occur, patients should abandon such activities until they are convinced that these symptoms do not have a significant effect on them.

Form release / dosage:

Film-coated tablets, 250 mg, 500 mg, 750 mg and 1000 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 30 tablets in a jar of polymer materials.

Each jar or 3 or 6 contour packs of 10 tablets together with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003652

Date of registration:26.05.2016

Expiration Date:26.05.2021

The owner of the registration certificate:VEROPHARM SA VEROPHARM SA Russia

Manufacturer: & nbsp

VEROPHARM SA Russia

Representation: & nbspVEROPHARM, AO VEROPHARM, AO Russia

Information update date: & nbsp02.01.2018

Illustrated instructions

Instructions

Kepayra Vero® (Kepayra Vero®)