Universal reference book for medicines
Product name: LEVETHINOL ® (LEVETINOL)

Active substance: levetiracetam

Type: Anticonvulsant drug

Manufacturer: GEROFARM (Russia) manufactured by ACTAVIS hf.(Iceland)
Composition, form of production and packaging
The tablets covered with a film shell of
blue color, oval, biconcave, marked on one side by engraving "L", on the other - "250";
on the fracture - the core of white or white with a yellowish hue of color.
1 tab.

levetiracetam 250 mg

Excipients: crospovidone - 8.25 mg, povidone - 7 mg, silicon dioxide colloidal anhydrous - 3.5 mg, magnesium stearate - 1.25 mg, film coating Opadrai ® II Blue 85F20440 (polyvinyl alcohol partially hydrolysed - 40%, titanium dioxide (E171) - 22.29 %, macrogol 4000 - 20.2%, talc - 14.8%, dye indigo carmine (E132) - 2.71%) - 8.1 mg.

10 pieces.
- blisters (3) - packs of cardboard.
10 pieces.
- blisters (6) - packs of cardboard.
30 pcs.
- polymer cans (1) - packs of cardboard.
60 pcs.
- polymer cans (1) - packs of cardboard.
The tablets covered with a film cover of yellow color, oval, biconcave, marked on one side by engraving "L", with another - "500";
on the fracture - the core of white or white with a yellowish hue of color.
1 tab.

levetiracetam 500 mg

Excipients: crospovidone - 16.5 mg, povidone - 14 mg, silicon dioxide colloidal anhydrous - 7 mg, magnesium stearate - 2.5 mg, film coating Opadrai ® II Yellow 85F32371 (polyvinyl alcohol partially hydrolysed - 40%, titanium dioxide (E171) - 23.92 %, macrogol 4000 - 20.2%, talc - 14.8%, dye indigo carmine (E132) - 0.11%, iron coloring oxide yellow (E172) - 0.97%) - 16.2 mg.

10 pieces.
- blisters (3) - packs of cardboard.
10 pieces.
- blisters (6) - packs of cardboard.
30 pcs.
- polymer cans (1) - packs of cardboard.
60 pcs.
- polymer cans (1) - packs of cardboard.
The tablets covered with a film cover of light orange color, oval, biconcave, marked on one side by engraving "L", on the other - "750";
on the fracture - the core of white or white with a yellowish hue of color.
1 tab.

levetiracetam 750 mg

Excipients: crospovidone - 24.75 mg, povidone - 21 mg, silicon dioxide colloidal anhydrous - 10.5 mg, magnesium stearate - 3.75 mg, film coating Opadrai ® II Orange 85F23648 (polyvinyl alcohol partially hydrolysed - 40%, titanium dioxide (E171) - 24.22 %, macrogol 4000 - 20.2%, talc - 14.8%, dye indigo carmine (E132) - 0.01%, dye sunset yellow (E110) - 0.64%, ferric oxide red oxide (E172) - 0.13%) - 24.3 mg.

10 pieces.
- blisters (3) - packs of cardboard.
10 pieces.
- blisters (6) - packs of cardboard.
30 pcs.
- polymer cans (1) - packs of cardboard.
60 pcs.
- polymer cans (1) - packs of cardboard.
The tablets covered with a film shell of white color, oval, biconcave, marked on one side by engraving "L", on the other - "1000";
on the fracture - the core of white or white with a yellowish hue of color.
1 tab.

levetiracetam 1000 mg

Excipients: crospovidone 33 mg, povidone 28 mg, silicon dioxide colloidal anhydrous 14 mg, magnesium stearate 5 mg, film coating Opadrai II II White 85F18422 (polyvinyl alcohol partially hydrolysed 40%, titanium dioxide (E171) 25 %, macrogol 4000 - 20.2%, talcum - 14.8%) - 32 mg.

10 pieces.
- blisters (3) - packs of cardboard.
10 pieces.
- blisters (6) - packs of cardboard.
30 pcs.
- polymer cans (1) - packs of cardboard.
60 pcs.
- polymer cans (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2017.

PHARMACHOLOGIC EFFECT

Anticonvulsant drug.
Levetiracetam, the active substance of the preparation Levetinol ® , is a derivative of pyrrolidone (S-enantiomer? -ethyl-2-oxo-1-pyrrolidineacetamide), in chemical structure differs from other anticonvulsants.
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 it was shown that levetiracetam does not affect the basic properties of the cell and normal nervous transmission.
In vitro studies have shown that, partially reducing the N-type calcium currents and reducing the release of calcium ions from the intracellular neuronal depot, levetiracetam changes the concentration of calcium ions inside the neurons.
In addition, it partially eliminates the decrease in the currents of GABA and Glycine channels caused by zinc and β-carbolines. Moreover, in in vitro studies It is shown that levetiracetam binds to specific parts 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 of 2A synaptic vesicles exhibit anticonvulsant activity on 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 synaptic vial protein 2A realizes its anticonvulsant action.
Levetiracetam has an anticonvulsant effect on many models of partial and primarily generalized convulsions 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 burst / photoparosymal response), which confirms its wide spectrum of pharmacological action.

PHARMACOKINETICS

Levetiracetam is a well-soluble and permeable compound.
The pharmacokinetic profile is linear in nature with a low intra- and interindividual variation. After long-term use, there is no change in 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 for 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 ratio ranges from 1-1.7 for oral tablets and for oral administration 4 hours after ingestion).

Adults and teenagers

Suction

After oral administration, levetiracetam is rapidly absorbed.
Absolute bioavailability after oral administration is close to 100%. C max is achieved after 1.3 hours. The equilibrium state is achieved after 2 days with the drug taken 2 times / day.
C max is usually 31 and 43 μg / ml after a single dose of 1000 mg and a dose of 1000 mg twice a day.

The amount 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%).

V d of levetiracetam is about 0.5-0.7 l / kg, which roughly corresponds to the volume of water in the body.

Metabolism

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 due to the hydroxylation of the pyrrolidone ring (1.6% of the dose), the second by the opening of 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 was not detected.
Levetiracetam and its main metabolite do not inhibit the main isoenzymes of human cytochrome P450 (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 the isoenzymes CYP1A2, SULT1E1 and UGT1A1.
Levetiracetam weakly induced the activity of the isoenzymes CYP2B6 and CYP3A4. Data on the 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

T 1/2 in adults is 7 ± 1 and does not depend 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% is excreted within 48 hours).
Excretion with feces is only 0.3% of the dose.
The total excretion of levetiracetam and its main metabolite is 66% and 24%, respectively, for the first 48 hours. The renal clearance of levetiracetam and ucb L057 is 0.6 and 4.2 ml / min / kg, respectively, indicating the excretion of levetiracetam by glomerular filtration with subsequent tubular reabsorption, and the main metabolite, along with glomerular filtration - active tubular secretion.

Elimination of levetiracetam correlates with QC.

Pharmacokinetics in special clinical cases

T 1/2 in the elderly is increased by 40% (up to 10-11 h), which is due to a decrease in kidney function in this population.

The apparent clearance of levetiracetam and its main metabolite depends on QC.
Therefore, in patients with moderate and severe renal insufficiency, it is recommended to adjust the maintenance dose of the drug depending on the CK.
In adult patients with terminal renal failure, T 1/2 is 25 hours between hemodialysis sessions and 3.1 hours during the procedure.

During a typical 4-hour hemodialysis session, about 51% of levetiracetam is removed.

In patients with mild to moderate hepatic insufficiency, the clearance of levetiracetam varies insignificantly.
In most patients with severe hepatic insufficiency, the clearance of levetiracetam declines by more than 50%, due to concomitant renal failure.
After a single dose of 20 mg / kg T 1/2 in children 6-12 years is 6 hours. The body weight corrected apparent apparent clearance is 30% higher than that of 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. C max is achieved within 0.5-1 h. C max and AUC are linear and proportional to the dose. The terminal T 1/2 is 5 hours. The apparent clearance is 1.1 ml / min / kg.
INDICATIONS

As a monotherapy for the treatment of partial seizures with secondary generalization or without it in patients with 16 years of age with a newly diagnosed epilepsy.

As an auxiliary therapy levetiracetam is indicated for treatment of:

- partial seizures with secondary generalization or without it in patients with epilepsy from age 6;

- myoclonic seizures in patients with juvenile myoclonic epilepsy from age 12;

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

DOSING MODE

Monotherapy in adults and adolescents with 16 years

The recommended initial dose is 250 mg 2 times / day, which must be increased 2 weeks before the initial therapeutic 500 mg 2 times / day.
The dose can be increased in steps of 250 mg 2 times / day every 2 weeks, depending on the clinical response. The maximum dose is 1500 mg 2 times / day.
Auxiliary therapy in adults (? 18 years) and adolescents (12-17 years) with a body weight of 50 kg and more

The initial therapeutic dose is 500 mg 2 times / 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 2 times / day.
The dose can be increased or decreased by 500 mg 2 times / day every 2-4 weeks.
Patients of advanced age (65 years and older)

In elderly patients with impaired renal function, it is recommended to adjust the dose of the drug.

Renal insufficiency

Depending on the degree of impaired renal function, the daily dose is selected individually.
To use the dose adjustment table, calculate the patient's QC in ml / min. QC 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):
KK (ml / min) = [140 - age (years)]?
body weight (kg) / 72 ° plasma creatinine concentration (mg / dL) (0.85 for women)
Then, correction for the body surface area (TFT) is introduced as follows:

KK (ml / min / 1.73 m 2 ) = SC (ml / min) / patient TFT (m 2 ) 1.73

Dose adjustment in adults and adolescents with renal dysfunction, whose body weight is> 50 kg

Group CK (ml / min / 1.73 m 2 ) Dose and frequency of admission

Norm> 80 500-1500 mg 2 times / day

Light 50-79 500-1000 mg 2 times / day

Medium degree 30-49 250-750 mg 2 times / day

Heavy <30 250-500 mg 2 times / day

Terminal stage of renal failure - patients on hemodialysis (1) - 500-1000 mg 1 time / day (2)

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

(2) Upon completion of hemodialysis, an additional 250 or 500 mg dose 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. SC in ml / min / 1.73 m 2 in children and adolescents can be estimated from the plasma creatinine concentration (in mg / dL) according to the following formula (Schwarz formula):
CK (ml / min / 1.73 m 2 ) = height (cm)? Ks / plasma creatinine concentration (mg / dL)

where ks = 0.45 for children under the age of 1 year;
0.55 - for children aged 1-13 years and females; 0.7 - adolescent male.
Correction of the dose in children and adolescents with impaired renal function, whose body weight is <50 kg

Group CK (ml / min / 1.73 m 2 ) Dose and frequency of admission from 6 years

Norm> 80 10-30 mg / kg 2 times / day

Light 50-79 10-20 mg / kg 2 times / day

Medium degree 30-49 5-15 mg / kg 2 times / day

Heavy <30 5-10 mg / kg 2 times / day

Terminal stage of renal failure - patients on hemodialysis (1) 10-20 mg / kg 1 time / day (2) (3)

(1) The oral solution is used for doses of <250 mg and in patients who are unable to swallow tablets.

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

(3) Upon 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 CC <60 ml / min / 1.73 m 2 , the maintenance dose of the drug should be reduced 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 dosage of tablets is not intended for initial dose selection in children weighing less than 25 kg, patients who are unable to swallow tablets, and also if necessary to take a dose of <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 6-17 years old and with a body weight of less than 50 kg

The initial dose is 10 mg / kg 2 times / day.
Depending on the clinical response and tolerability, the dose may be increased to 30 mg / kg 2 times / day. The dose may be increased or decreased in steps of 10 mg / kg 2 times / day every 2 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 from 6 years of age

Body weight Initial dose: 10 mg / kg 2 times / day Maximum dose: 30 mg / kg 2 times / day

25 kg (1) 250 mg 2 times / day 750 mg 2 times / day

from 50 kg (2) 500 mg 2 times / day 1500 mg 2 times / day

(1) For children with a body weight of 25 kg or less, it is recommended that the drug be administered in a dosage form for oral administration, 100 mg / ml

(2) The dosage regimen in children weighing 50 kg or more is not different from adults.

The drug is taken orally with a sufficient amount of water, regardless of food intake.
The daily dose is divided into 2 equal doses.
SIDE EFFECT

The adverse event profile presented below is based on the analysis of 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 also does not depend on approved indications for use (various variants of epilepsy).
Adverse events found in clinical trials and post-registration monitoring (in adults, adolescents and children over 1 month of age) 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).
Very often Often infrequently Rarely

Infections and invasions

nasopharyngitis infection

On the part of the hematopoiesis system

thrombocytopenia, leukopenia 1 pancytopenia 1,2 , neutropenia 1

From the side of metabolism

anorexia depression 1 or weight gain

From the side of the psyche

depression, hostility or aggression 1 , insomnia, nervousness, irritability, suicidal attempts 1 , suicidal thoughts 1 , psychotic disorders 1 , conduct disorder 1 , hallucination, anger, confusion, emotional lability, mood changes, agitation held suicide 1 , personality disorder, abnormal thinking
nervous system
drowsiness, headache, convulsions, impaired balance, dizziness, lethargy, tremor amnesia, memory impairment, impaired coordination or ataxia, aresteziya 1 , attention disorders choreoathetosis 1 , dyskinesia1 , hyperkinesia
part of the vision
diplopia, blurred vision
part of the organ of hearing and balance
vertigo
Respiratory system
cough
Digestive system
stomach pain, diarrhea, dyspepsia, vomiting, nausea Pancreatitis 1
Liver and Biliary
violation of liver function tests 1 liver failure 1 , hepatitis 1
skin and subcutaneous tissue
rash alopecia 1 , eczema, itching, toxic epidermal necrolysis 1 , Stevens-Johnson syndrome, erythema multiforme 1
From the musculoskeletal system
muscle weakness, myalgia
, Common disorders
asthenia fatigue or injury
1 Adverse reactions identified in the post-registration period 2 In some cases, inhibition of bone marrow hematopoiesis set
Description of individual adverse reactions
In an application of topiramate, and levetiracetam increases the risk of anorexia.
In some cases, alopecia regress after discontinuation of levetiracetam.
Children

As part of the placebo-controlled and open studies are extended treatment of 645 patients aged 4-16 years, 233 of whom received levetiracetam as part of placebo-controlled studies. For both age ranges further data are available for post-registration experience levetiracetam.
The safety profile of levetiracetam in general does not differ according to age (adults and children), and are not dependent on the approved indication for use of (different variants of epilepsy). Except for behavioral and psychiatric adverse reactions, which occurred more frequently in children than in adults, in the placebo-controlled studies, the safety profile of levetiracetam in children was comparable to that in adults. In children aged 4-16 years, vomiting (very common, 11.2%), agitation (common, 3.4%), mood changes (often 2.1%), emotional lability (common, 1.7%), aggression (common, 8.2%) , conduct disorder (often 5.6%) and lethargy (common, 3.9%) were more frequent than in other age ranges.
Cognitive and neuropsychological effects of levetiracetam in children 4-16 years with partial seizures were evaluated in a double-blind, placebo-controlled studies, the safety profile with the use of the design is not less secure. It was demonstrated that levetiracetam is different (not less secure) from placebo in change from baseline on scale "attention and memory Leiter-R" (Leiter-R Attention and Memory), a scale "Integrated Monitoring of Memory" (Memory Screen Composite) in patients undergoing analysis "protocol". Results of the study of behavioral and emotional functions, confirming that treatment with levetiracetam there is aggressive behavior,obtained using a standardized method using a validated instrument - Questionnaire behavior Achenbach children (Achenbach Child Behavior Checklist).
However, in patients treated with levetiracetam in the framework of long-term open-label studies, behavioral and emotional disorders functions did not arise, in particular the level of aggressive behavior was no different from the original.
CONTRAINDICATIONS

- children's age till 6 years;

- hypersensitivity to the components of the drug;

- Hypersensitivity to derivatives of pyrrolidone.
PREGNANCY AND LACTATION

Data on the use of levetiracetam during pregnancy are insufficient. In animal studies demonstrated the existence of reproductive toxicity. The potential risk for humans is not known.
Use of the drug during pregnancy and in women of childbearing age who are not using reliable methods of contraception, only in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus.
As with other anticonvulsant drugs, physiological changes during pregnancy may affect levetiracetam concentration. In pregnancy, there is a decrease plasma concentrations of levetiracetam. This decrease is most pronounced during the III trimester (up to 60% of the baseline concentration observed before pregnancy). For pregnant women, receiving levetiracetam should establish a proper lookout. Cancel anticonvulsant therapy may lead to an aggravation of the disease, which could negatively affect the state of the mother and fetus.
Levetiracetam is excreted in breast milk. Breast-feeding is not recommended during treatment. However, if levetiracetam treatment should continue during breastfeeding, it is necessary to correlate the expected benefits and possible risks of treatment and the importance of breastfeeding.
The study found no effect on animal fertility. The clinical data are available, potential risk for humans is not known.
APPLICATION FOR FUNCTIONS OF THE LIVER

Depending on the degree of impairment of renal function the daily dose picked individually.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

In patients with mild to moderate hepatic impairment dose adjustment is required.
APPLICATION FOR CHILDREN

The drug is administered 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 under the age of 6 years. Such patients recommended to assign the drug in the dosage form for oral solution. Also available dosage tablets not intended for initial adjustment of the dosage for children weighing less than 25 kg, patients unable to swallow tablets, and optionally dosing <250 mg. In all these cases it is recommended to use the solution for intake.
APPLICATION IN ELDERLY PATIENTS

In elderly patients with impaired renal function is recommended to adjust the dose as in renal failure.
SPECIAL INSTRUCTIONS

Cancel therapy
Abolition of the drug is recommended to be gradual. For example, for adults and adolescents weighing more than 50 kg of a reduced dose should be administered at 500 mg two times / day no more frequently than every 2-4 weeks; in children from 6 years weighing less than 50 kg dose reduction should be carried out in increments of no more than 10 mg / kg 2x / day no more frequently than every 2 weeks.
Renal failure
Application levetiracetam in patients with renal failure may require dosage adjustment. In patients with severe hepatic impairment it is recommended to evaluate kidney function prior to dose selection.
suicide
Patients taking anticonvulsants (including levetiracetam), observed suicide, suicide attempt, suicidal thoughts and behavior. Meta-analysis of randomized placebo controlled trials of anticonvulsant drugs showed a slight increase in risk of suicidal thoughts and behavior. The mechanism of its realization is not known.
In view of the above, it is necessary to monitor the patient with symptoms of depression or suicidal thoughts and behavior and assign them to the appropriate treatment. Patients (and caregivers of them) should be informed of the need to seek medical care in the event of their depressive symptoms and (or) suicidal thoughts and behavior.
Use in Pediatrics

Tablets are not intended for use in children under the age of 6 years.
According to reports levetiracetam does not affect the growth and sexual maturation. However, long term effects on learning, intelligence, growth, endocrine function, puberty and fertility in children is not known.
Impact on the ability to drive vehicles and manage mechanisms

Studies on the effects on ability to drive and operate machinery have not been conducted.
Due to individual differences in susceptibility, some patients may experience drowsiness or other disorders of the central nervous system, especially at the beginning of treatment and after dose escalation. Therefore it is recommended to use caution when driving and occupation of other activities that require high concentration and psychomotor speed reactions. If you experience these symptoms, patients should abandon such activities until they are convinced that these symptoms do not have a significant impact on them.
OVERDOSE

Symptoms: drowsiness, agitation, aggression, depression of consciousness, respiratory depression and coma.
Treatment: after an acute overdose is necessary to wash out the stomach and cause vomiting. Antidote levetiracetam was not found. Treatment is symptomatic, may include application of hemodialysis. Activity dialyzed against levetiracetam is 60% with respect to the major metabolite - 74%.
DRUG INTERACTION

Anticonvulsants
According to the pre-registration clinical trials of levetiracetam does not affect the serum concentrations of other anticonvulsant drugs: phenytoin, carbamazepine, valproic acid, phenobarbital, lamotrigine, gabapentin and primidone, and these anticonvulsants do not affect the pharmacokinetics of levetiracetam.
Similarly, adults, children in doses up to 60 mg / kg / day levetiracetam does not interact with other drugs. Retrospective assessment of pharmacokinetic interactions in children and adolescents with epilepsy (4-17 years) confirms that levetiracetam as adjunctive therapy has no effect on the C sssimultaneously applied carbamazepine and valproic acid. However, there is evidence that levetiracetam clearance in children taking anticonvulsants - inducers of microsomal liver enzymes, increased by 20%. No dose adjustment is required.
probenecid
Probenecid (500 mg four times / day) is a blocker of renal tubular secretion is shown that it inhibits the renal clearance of the major metabolite, but not levetiracetam. Nevertheless, the main metabolite concentration remains low. It is expected that other drugs are excreted via active tubular secretion, may decrease renal clearance of the main metabolite. Effect of levetiracetam on probenecid was not studied; effect of levetiracetam on other drugs excreted by active tubular secretion, including NSAIDs, sulfonamide and methotrexate is not known.
Oral contraceptives, digoxin and warfarin
Levetiracetam 1000 mg / day had no effect on the pharmacokinetics of oral contraceptives (ethinyl estradiol and levonorgestrel); hormonal status (the content of LH and progesterone) is not changed.
Levetiracetam 2000 mg / day had no effect on the pharmacokinetics of digoxin and warfarin, the prothrombin time did not change. Concomitant use of digoxin, oral contraceptives and warfarin do not affect the pharmacokinetics of levetiracetam.
Antacids

Data on the influence of antacids on the absorption of levetiracetam are absent.
Food and drink
Food does not affect the extent of absorption of levetiracetam, but slightly reduces its speed.
Data on the interaction of levetiracetam with no ethanol.
TERMS OF RELEASE FROM PHARMACY

The drug is released by prescription.

TERMS AND CONDITIONS OF STORAGE

The drug should be kept out of the reach of children, dry, dark place at a temperature not higher than 25 ° C.
Shelf life - 3 years.
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