Levetiracetam - instructions for use, dose, side effects, contraindications

Excipients: corn starch 13,650 mg, croscarmellose sodium 5,600 mg, povidone K-17 5,600 mg, silicon dioxide colloid 1,790 mg, talc 1,680 mg, magnesium stearate 1,680 mg, Opadry II blue 85F20694 - 7.00 mg: polyvinyl alcohol (E1203) 2.800 mg, titanium dioxide (E171) 1.560 mg, macrogol (E1521) 400 1.410 mg, talc (E553b) 1.040 mg, indigo carmine (E132) 0.190 mg.

IN 1 tablet 500 mg contains:

active substance: levetiracetam 500 mg;

Excipients: corn starch 27,300 mg, croscarmellose sodium 11,200 mg, povidone K-17 11,200 mg, silicon dioxide colloid 3,580 mg, talcum powder 3,360 mg, magnesium stearate 3,360 mg, Opadry II yellow 85F32004 - 14.00 mg: polyvinyl alcohol (E1203) 5,600 mg, titanium dioxide (E171) 3.349 mg, macrogol (E1521) 400 2,828 mg, talc (E553b) 2.072 mg, ferric iron oxide yellow (E172) 0.151 mg.

IN 1 750 mg tablet contains:

active substance: levetiracetam 750 mg;

Excipients: corn starch 40,950 mg, croscarmellose sodium 16,800 mg, povidone K-17 16,800 mg, silicon dioxide colloid 5,370 mg, talc 5,040 mg, magnesium stearate 5,040 mg, Opadry II Orange 85F23452 - 21.00 mg: polyvinyl alcohol (E1203) 8,400 mg, titanium dioxide (E171) 5,040 mg, macrogol (E1521) 400 4,242 mg, talc (E553b) 3,108 mg, ferric iron oxide red (E172) 0.042 mg, dye solar sunset yellow (E110) 0.168 mg.

AT 1 tablet of 1000 mg contains:

active substance: levetiracetam 1000 mg;

Excipients: corn starch 54,600 mg, croscarmellose sodium 22,400 mg, povidone K-17 22.40 mg, silicon dioxide colloid 7,160 mg, talc 6,720 mg, magnesium stearate 6,720 mg, Opadry II white 85F18422 - 28 mg: polyvinyl alcohol (E1203) 11,200 mg, titanium dioxide (E171) 7,000 mg, macrogol 400 (E1521) 5.666 mg, talc (E553b) 4.144 mg.

Description:

Tablets 250 mg

Tablets are blue, elongated, with a risk, covered with a film shell, engraved on one side, "H" side, on the other "87". On the cross-section - the core is white or almost white.

Tablets 500 mg

Tablets of yellow color, oblong form, with a risk, covered with a film shell, with engraving on one side of the "H", on the other - "88". On the cross-section - the core is white or almost white.

Tablets 750 mg

Tablets of orange color, oblong form, with a risk, covered with a film shell, with engraving on one side of the "H", on the other "90". On the cross-section - the core is white or almost white.

Tablets 1000 mg

Tablets of white color, oblong form, with a risk, covered with a film sheath, engraved on one side of the "H", on the other "91". On the cross-section - the core is white or almost white.

Pharmacotherapeutic group:antiepileptic agent

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), according to chemical structure different 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 2A protein of 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.

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 concentrationis 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 (the ratio of saliva / plasma ranges from 1-1.7 for oral tablets and forsolution for oral administration four hours after the administration of the latter).

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_mOhis usually 31 and 43 μg / ml after a single dose of 1000 mg and a dose of 1000 mg twice a day.

Absolute valuerbtion is independent of dose and from food intake.

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 the opening of the pyrrolidone ring (0.9% dose).

Other unidentified metabolites are only 0.6% 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 valproic acid glucuronucleation in vitro.

In hepatocyte culturein the foreheadcenturies levetiracetam had little or no effect on the activity of isoenzymes CYP1 A2, 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 h 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% output within 48 hours). Excretion with faeces is only 0.3% of the dose.

The total excretion of levetiracetam and its main metabolite is 66 and 24%, respectively, 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 of the main metabolite by with classby tubular filtration - active tubular secretion.

Elimination of levetiracetam correlates with creatinine clearance.

Elderly

The half-life in the elderly is increased by 40% (up to 10-11 h), which is due to a decrease in kidney function in this population group.

Renal insufficiency

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

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 four-hour hemodialysis session, about 51% of levetiracetam is removed.

Impaired liver function

In patients with mild and moderate hepatic insufficiency, the clearance of levetiracetam varies slightly. In most patients with severe hepatic insufficiency, the clearance of levetiracetam declines by more than 50%, due to concomitant renal failure.

Children under 12 years of age

Children aged 4-12 years

After a single dose of 20 mg / kg, the half-life in children 6-12 years is 6 hours. The body weight corrected apparent apparent clearance by 30% exceeds 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.

Indications:

The levetiracetam is shown 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:

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

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

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

Contraindications:

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

Children under 6 years.

Pregnancy and lactation:

Pregnancy

Data on the use of levetiracetam during pregnancy are not enough. In animal studies, the presence of reproductive toxicity is indicated. The potential risk to humans is unknown.

It is recommended to use levetiracetam during pregnancy, as well as in fertile women who do not use reliable methods of contraception, only with good reasons.

As with other anticonvulsants, 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 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.

Specials groups patients

Elderly (65 years and over)

In elderly patients with impaired renal function, it is recommended that the dose be adjusted (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.

The 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 and more):

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

Зin thethe correction for the surface area of the body (PPT) is as follows:

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

Correction of dose in adults and adolescents with impaired renal function, body weight> 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 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.

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) × ks / plasma creatinine concentration (mg / dL)

Where ks= 0.45 for children up to 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	KK (ml / min / 1.73 m² )	Dose and frequency of admission from 6 years
Norm	>80	10-30 mg / kg 2 times a day
Lightweight	50-79	10-20 mg / kg 2 times a day
Medium	30-49	5-15 mg / kg 2 times per day
Heavy	<30	5-10 mg / kg 2 times a day
Terminal stage, renal, insufficiency - patients on hemodialysis (1)		10-20 mg / kg once a 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) At the end 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 and moderate degree of 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 K <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 is recommended to be administered in the form of a solution 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 a day.

Depending on the clinical response and tolerability, the dose is allowed to be increased to 30 mg / kg 2 times a day. The dose can be increased, or reduced 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 from 6 years of age:

Body mass	Initial dose: 10 mg / kg 2 times a day	Maximum dose: 30 mg / kg once daily
25 kg⁽¹⁾	250 mg twice daily	750 mg twice a day
From 50 kg⁽²⁾	500 mg twice a day	1500 mg twice a day

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

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

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 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).

This data is supplemented by aabout application of levetiracetam in the framework 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).

Table data on adverse reactions

Undesirable reactions revealed in clinical trials and in the framework of post-registration monitoring (in adults, adolescents and children over the first 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	Frequency Category
System-Organ Class	Often	Often	Infrequently	Rarely
Infections and invasions	Nasopharyngitis			Infections
From the side blood and lymphatic system			Thrombocytopenia, leukopenia¹	Pancytopenia^1,2, neutropenia¹
Metabolism and nutrition disorders		Anorexia	Decrease¹ or weight gain
Mental violations		Depression, hostility or aggression¹, sleep disturbance, nervousness, irritability	Suicidal attempts¹, suicidal thoughts¹, psychotic disorders¹, behavioral disorders¹, hallucinations, anger, confusion, emotional lability, mood changes, agitation	The suicide¹, personality disorder, thinking disorder
From the nervous system	Drowsiness, headache	Convulsions, imbalance, dizziness, lethargy, tremor	Amnesia, memory impairment, movement coordination disorder or ataxia, paresthesia¹, attention deficit disorder	Choreoathetosis¹, dyskinesia¹, hyperkinesia
From the side of the organ of vision			Diplopia, blurred vision
From the side of the organ of hearing and balance		Vertigo
From the side respiratory system, chest and mediastinal organs		Cough
From the gastrointestinal tract		Abdominal pain, diarrhea, indigestion, vomiting, nausea		Pancreatitis¹
From the liver and biliary tract			Violation of functional liver tests¹	Hepatic failure¹, hepatitis¹
From the skin and subcutaneous tissues		Rash	Alopecia¹, eczema, itching	Toxic epidermal necrolysis¹, Stevens-Johnson syndrome, erythema multiforme¹
From the musculoskeletal and connective tissues			Muscle weakness, myalgia
Are common disorders and disorders at the site of administration		Asthenia or fatigue
Injuries, poisonings and complications procedures			Injury

¹Undesirable reactions identified in the post-marketing period

² In some cases, oppression of bone marrow hematopoiesis has been established

Description of individual adverse reactions

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

In some cases of alopecia, it was reversed after the removal of levetiracetam.

Children

Within the 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, there are additional data on post-marketingy experiencefor levetiracetam.

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). 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 observed more often than in other age ranges.

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 not 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 subjected to analysis "by protocol." The results of a study of behavioral emotional functions confirming that aggressive behavior develops against the background of the use of levetiracetam are obtained using a standardized method with the use of a validated instrument, the Achenbach 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.

Overdose:

Symptoms

Drowsiness, agitation, aggression, oppression of consciousness, respiratory depression and coma.

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:

Anticonvulsantmeals

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

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 ofagaino 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, sulfonamide 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 of 2000 mg per day did not affect 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.

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 from 6 years of age with a body weight of less than 50 kg, dose reduction should be carried out in increments of no more than 10 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 the start of dose selection (see Fig.See section "Dosing and Administration").

Suicide

In patients taking anticonvulsants (including levetiracetam), there was suicide, suicide attempts, suicidal thoughts and behavior. Meta-analysis, a randomized, placebo-controlled study of anticonvulsant drugs showed a slight increase in the risk of suicidal ideation andof the information. The mechanism of its implementation is unknown.

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.

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 other types of activities, activities that require increased concentration of attention and the speed of psychomotor reactions. When the occurrence of these symptoms patients should refuse 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:

When manufacturing on Hetero Labe Limited

For 10 tablets in aluminum / PVC / PVDC / blister.

For 10 tablets in aluminum / PVC / blister.

For 3 or 6 blisters with instructions for use in a pack of cardboard.

Packaging in-bulk

For 1000 tablets in triple laminated aluminum package.

10 to 30 hermetically sealed triple laminated aluminum bags in a package of air-bubble film. 1 packet of air-bubble film into a drum of high-density polyethylene.

For 10-30 blisters are placed in a pack of cardboard. For 40-70 packs are placed in a box of cardboard. On the box and the box are labeled.

In production, packaging and / or packaging at LLC "MAKIZ-PHARMA"

10 tablets in a planar cell pack from a film of PVC and foil of aluminum printed varnished.

For 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 expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001606

Date of registration:23.03.2012 / 14.01.2016

Expiration Date:23.03.2017

The owner of the registration certificate:Heterose Labs LimitedHeterose Labs Limited India

Manufacturer: & nbsp

MAKIZ-PHARMA, LLC Russia

HETERO LABS, Limited India

Representation: & nbspHeterose Labs LimitedHeterose Labs LimitedIndia

Information update date: & nbsp22.10.2016

Illustrated instructions

Instructions

Levetiracetam (Levetiracetam)