Keppra

Keppra – anticonvulsant, antiepileptic drug, active in the relation of both generalized, and focal epileptic seizures.

Form of release and structure

Keppra is let out in the following dosage forms:

• Concentrate for preparation of solution for infusions: transparent colourless solution (on 5 ml in glass bottles, on 5 bottles in blister strip packagings, on 2 packagings in a cardboard pack);
• Tablets, film coated (blue – 250 mg, light yellow – 500 mg, white – 1000 mg): an oval form, biconvex, on one of the parties – risk, "ucb" dividing an engraving and a dosage (ucb|250, ucb|500, ucb|1000), on a break white, homogeneous (on 10 pieces in blisters/blister strip packagings, on 3 or 6 blisters/packagings in a cardboard pack);
• Solution for intake: transparent, almost colourless liquid with a characteristic smell (on 300 ml in bottles from dark glass complete with the screw-on cover from white polypropylene with function of protection against children and the measured syringe (polyethylene/polystyrene), on 1 set in a cardboard pack).

For preparation of infusion solution is a part of 5 ml of a concentrate:

• Active agent: to levetiratseta – 500 mg;
• Auxiliary components: sodium chloride – 45 mg, trihydrate sodium acetate – 8,2 mg, 10% glacial acetic acid – before achievement рН 5,5, water for injections – to 5 ml.

Is a part of 1 tablet:

• Active agent: to levetiratseta – 250 mg, 500 mg, 1000 mg;
• Auxiliary components (250/500/1000 mg respectively): silicon dioxide – 5,188/10,375/20,75 mg, croscarmellose sodium – 10,75/21,5/43 mg, a macrogoal of 6000 - 2,5/5/10 mg, magnesium stearate – 0,313/0,625/1,25 mg;
• Film cover (250/500/1000 mg respectively): Opadry 85F20694 – 8,063 of mg / Opadry 85F32004 – 16,125 of mg / Opadry 85F18422 – 32,25 of mg.

For oral administration is a part of 1 ml of solution:

• Active agent: to levetiratseta – 100 mg;
• Auxiliary components: sodium citrate – 1,05 mg, monohydrate of citric acid – 0,06 mg, methylparahydroxybenzoate – 2,7 mg, пропилпарагидроксибензоат – 0,3 mg, глицирризат ammonium – 1,5 mg, 85% глицерол – 235,5 mg, мальтитол – 300 mg, to potassium atsesulfa – 4,5 mg, grape fragrance 501040A - 0,3 of mg, the purified water – 504 mg.

Indications to use

Keppra along with other drugs is applied to treatment of the following states / diseases:

• Epilepsy: partial attacks with secondary generalization or without at adults and children are more senior than 1 month (solution for oral administration), 4 years (infusion solution, tablets);
• Juvenile myoclonic epilepsy: myoclonic spasms at adults and children are more senior than 12 years;
• Idiopathic generalized epilepsy: primary and generalized convulsive (toniko-clonic) attacks at adults and children are more senior than 12 years.

As monotherapy (choice drug) Keppra is used at partial attacks with secondary generalization or without at adults and teenagers from 16 years with for the first time the diagnosed epilepsy.

The concentrate to preparation of solution for infusions is applied temporarily when the peroral forms of medicine cannot be taken for any reason.

Contraindications

• Children's age: up to 1 month – solution for oral administration (efficiency and safety of use of drug are not established), up to 4 years – infusion solution, tablets;
• Hypersensitivity to derivatives of a pirrolidon including a levetiratsetam, and also other components.

With care therapy by Keppra is carried out at patients at advanced age (of 65 years), at liver diseases to stages of a decompensation and a renal failure.

Route of administration and dosage

Duration of a course of treatment and the choice of a dosage form of Keppra is made by the attending physician.

Solution for intake, tablets, coated
Drug in the form of tablets or solution is accepted orally, dividing a daily dose into 2 equal receptions; tablets should be washed down with liquid in enough.

As choice drug for monotherapy of partial attacks with secondary generalization or without at adults and teenagers 16 years are more senior: an initial dose – 500 mg a day, divided into 2 receptions on 250 mg. 2 weeks later the dose can be increased to basic therapeutic – 1000 mg the day divided into 2 receptions on 500 mg. The maximum daily dose – 3000 mg divided into 2 receptions on 1500 mg.

As a part of complex therapy to children of 1 month before half a year to Keppr 2 times a day appoint in the form of solution for intake in an initial therapeutic dose 7 mg/kg. Depending on clinical performance and portability the dose can be increased to 21 mg/kg 2 times a day. Change of a dose a plus-minus of 7 mg/kg 2 times a day each 2 weeks before achievement of a minimal effective dose is allowed.

The recommended dosing of solution for intake to children before half a year – 2 times a day, depending on the body weight of the child (an initial dose / the maximum dose):

• 4 kg – 28-84 mg (0,3-0,85 ml);
• 5 kg – 35-105 mg (0,35-1,05 ml);
• 7 kg – 49-147 mg (0,5-1,5 ml).

At children and teenagers aged from half a year up to 17 years, with body weight to 50 kg, therapy there begin with a dose 10 mg/kg 2 times a day. Depending on portability of drug and clinical reaction the dose can be increased to 30 mg/kg 2 times a day (change of a dose on 10 mg/kg can be carried out each 2 weeks; it is necessary to use a minimal effective dose).

For children weighing 50 kg the mode of dosing same, as well as for adult patients is also more recommended.

The recommended drug dosing to children of half a year – 2 times a day, depending on the body weight of the child (an initial dose / the maximum dose):

• 6 kg – 60-180 mg (0,6-1,8 ml);
• 10 kg – 100-300 mg (1-3 ml);
• 15 kg – 150-450 mg (1,5-4,5 ml);
• 20 kg – 200-600 mg (2-6 ml);
• 25 kg – 250-750 mg;
• from 50 kg – 500-1500 mg.

To children 4 years are more senior it is necessary to begin therapy with the dose of 20 mg/kg a day divided into 2 receptions (10 mg/kg 2 times a day). Change of a dose on 20 mg/kg of body weight a day is carried out each 2 weeks before achievement of the recommended dose – 60 mg/kg a day (on 30 mg/kg 2 times a day). At intolerance of the recommended daily dose its decrease is possible. It is necessary to use a minimal effective dose.

Keppra is applied in the most suitable dosage and a dosage form depending on the weight of the patient and a required therapeutic dose.

Children weighing less than 20 kg are recommended to begin therapy with drug in the form of solution for intake.

Dosing of solution for intake is carried out the measured syringe with a nominal volume of 10 ml (1 g of the levetiratsetam) with scale interval of 25 mg (0,25 ml) which is included in the drug supply package. The drug dose measured for reception is parted in 200 ml of water.

The step-by-step instruction for dosing of solution for intake by means of the measured syringe:

1. To open Keppra's bottle, having pressed a cap and having turned it counterclockwise;
2. To insert the syringe adapter into a mouth of a bottle and, having convinced of good fixing, to place the syringe in the adapter;
3. To turn a bottle a mouth from top to bottom;
4. To gather a small amount of solution in the syringe, having pulled the piston down, further to press the piston up to remove vials of air;
5. To fill the syringe with solution, having pulled the piston down to the division corresponding to the dose appointed by the doctor;
6. To turn a bottle a bottom from top to bottom, to pull out the syringe from the adapter;
7. To enter syringe contents into a children's small bottle or glass with water, having pressed against the stop on the piston;
8. To completely drink contents of a children's small bottle or a glass;
9. To wash out the syringe water;
10. To close a bottle a plastic cover.

Infusion solution
The drug is administered intravenously kapelno within 15 minutes; the daily dose of solution is divided into 2 equal introductions.

Rolled into one a concentrate for preparation of solution for infusions 500 mg of a levetiratsetam (100 mg/ml) contain. The concentrate should be diluted with solvent not less than 100 ml.

The instruction for solution dosing (solvent volume – 100 ml, injection time – 15 min., introduction frequency – 2 times a day):

• 250 mg: 2,5 ml (^1/2 ampoules of 5 ml) – 500 mg a day;
• 500 mg: 5 ml (1 ampoule of 5 ml) – 1000 mg a day;
• 1000 mg: 10 ml (2 ampoules on 5 ml) – 2000 mg a day;
• 1500 mg: 15 ml (3 ampoules on 5 ml) – 3000 mg a day.

As solvents it is recommended to use: Ringer's solution lactat for injections, 0,9% sodium chloride solution for injections, 5% dextrose solution for injections.

Solution is chemically stable for 24 hours at a temperature of 15-25 °C in packages from polyvinylchloride. However from the point of view of microbiological sterility drug should be used right after cultivation.

If necessary solution can be stored at a temperature of 2-8 °C for days provided that dilution was made in aseptic conditions. Responsibility for microbiological purity is born at the same time by the user.

The mode of dosing of solution for infusions completely corresponds described for peroral forms. Transition from intravenous (to) introductions to oral administration of Keppra can be also back made with preservation of frequency rate of use and a dose.

Features of use of Keppra at a renal failure: as to levetiratseta it is brought out of an organism by kidneys, at purpose of drug elderly patients and patients with a renal failure need to make dose adjustment depending on the clearance of creatinine (CC).

For men of KK it is calculated on the following formula:

KK (ml/min.) = (140 - age (the number of years)) × the body weight (kg)/72×Cl (mg/dl.)

Cl – concentration of serumal creatinine.

For women of KK is calculated multiplication of the received result by coefficient 0,85.

Correction of KK value taking into account the body surface area (BSA):

Cl (ml/min.) of/1,73 ^sq.m = Cl (ml/min.) × 1,73/PPT ^(sq.m).

The recommended dosing mode depending on degree of a renal failure (KK value):

• Norm (KK more than 80) – 500-1500 mg 2 times a day;
• Latent (KK 50-79) – 500-1000 mg 2 times a day;
• Compensated (KK 30-49) – 250-750 mg 2 times a day;
• Intermittent (KK less than 30) – 250-500 mg 2 times a day;
• Terminal (patients on a hemodialysis) – 500-1000 mg once a day.

In the first day of therapy of the patients who are on a hemodialysis reception of sating Keppra's dose – 750 mg is recommended. Further, after carrying out dialysis, it is necessary to accept/enter in addition 250-500 mg of a levetiratsetam.

At a renal failure at children dose adjustment of a levetiratsetam is made taking into account the degree of a renal failure and recommendations made for adults.

Dose adjustment is not required at easy and moderate severity abnormal liver functions. In case of dekompensirovanny abnormal liver functions and a renal failure size KK can not reflect real degree of a renal failure therefore at KK less than 70 ml/min. it is necessary to reduce a daily dose by 50%.

Side effects

The most frequent undesirable reactions: drowsiness, nasopharyngitis, headache, dizziness and fatigue.

Side effects from systems and bodies depending on emergence frequency (≥1/10 – it is very frequent; ≥1/100-<1/10 – it is frequent; ≥1/1000-<1/100 – infrequently; ≥1/10 000-<1/1000 – it is rare; <1/10 000 – it is extremely rare):

• Gepatobiliarny system: infrequently – change of functional trials of a liver; seldom – hepatitis, a liver failure;
• Respiratory system: often – cough;
• Immune system: seldom – DRESS syndrome (a syndrome of the medicinal induced hypersensitivity with an eosinophilia);
• Invasions and infections: very often – a nasopharyngitis; seldom – infection;
• Integuments: often – rash; infrequently – eczema, an itch, an alopecia; seldom – Stephens-Johnson's syndrome, a toxic epidermal necrolysis, a mnogoformny erythema;
• Musculoskeletal system: infrequently – a mialgiya, muscular weakness;
• Blood and lymphatic system: infrequently – a leukopenia, thrombocytopenia; seldom – an agranulocytosis, a pancytopenia (in some episodes with oppression of function of marrow), a neutropenia;
• Nervous system: very often – a headache, drowsiness; often – disturbance of balance, a spasm, dizziness, a tremor, a lethargy; infrequently – a memory impairment, amnesia, disturbance a coordination/ataxy, decrease in concentration of attention, paresthesia; seldom – dyskinesia, a choreoathetosis, a hyperkinesia;
• Metabolism: often – anorexia; infrequently – decrease or increase in body weight;
• General frustration: often – adynamy/fatigue;
• Organ of sight: infrequently – a sight illegibility, a diplopia;
• Acoustic organ: often – dizziness (вертиго);
• Alimentary system: often – diarrhea, dyspepsia, an abdominal pain, nausea, vomiting; seldom – pancreatitis;
• Mental disorders: often – hostility/aggression, a depression, alarm, sleeplessness, irritability, nervousness; infrequently – suicide intentions, attempts of a suicide, behavioural frustration, psychotic frustration, hallucinations, confusion of consciousness, irascibility, emotional lability, excitement, changeability of mood, the panic attacks; seldom – personal disorder, disturbance of process of thinking, a suicide;
• Injuries, complications of procedures: infrequently – accidental damages.

In general profiles of safety of a levetiratsetam in various age groups of children and adults are similar.

After cancellation of a levetiratsetam in some cases recovery of indumentum was observed.

Special instructions

Under the influence of food completeness of absorption of a levetiratsetam does not change, but absorption speed decreases a little.

In case of need the terminations of administration of drug its cancellation are recommended to be carried out step by step (lowering a single dose each 2–4 weeks by 500 mg). The dose decline for children should not exceed 10 mg/kg 2 times a day each 2 weeks, and for children is younger than half a year – 7 mg/kg 2 times a day each 2 weeks.

During transfer of patients into reception of a levetiratsetam the accompanying antiepileptic drugs are recommended to be cancelled gradually.

There are no data at Keppra's use for the children testimonial of any negative influence on their puberty and development, but there are unknown remote effects of influence of a levetiratsetam on ability to training, growth, functions of closed glands, fertility, sexual and intellectual development of children.

At diseases of kidneys and dekompensirovanny diseases of a liver prior to therapy it is necessary to pass a research of function of kidneys, perhaps, drug dose adjustment will be required.

The patients who are on a diet with sodium restriction have to consider that in a concentrate for preparation of solution for infusions the content of sodium in 1 ampoule – 0,83 mmol (19 mg).

There are messages on cases of suicide intentions, a suicide and attempts of a suicide during therapy levetiratsetamy therefore it is necessary to warn patients about need immediately to report to the attending physician about emergence of any suicide intentions or symptoms of a depression.

There is no clinical experience of use of a levetiratsetam infusionally more than 4 days.

It is impossible to use drug in case of emergence in solution of mechanical inclusions or changes of its coloring.

Solution for intake is contraindicated to use at disturbance of tolerance to fructose because of the maintenance of a maltitol.

Content in solution for intake of a propilparagidroksibenzoat and methylparahydroxybenzoate can be the cause of an allergy (including the delayed action).

Considering individual sensitivity to a levetiratsetam from TsNS (drowsiness cases at some patients are recorded), during therapy it is necessary to abstain from the occupations demanding speed of psychomotor reactions and the increased concentration of attention including from driving of motor transport.

Medicinal interaction

• Antiepileptic drugs (carbamazepine, Phenytoinum, valproic acid, ламотриджин, phenobarbital, габапентин, Primidonum and топирамат): mutually do not influence concentration of each other in plasma;
• Anticonvulsants (inductors of microsomal enzymes of a liver): at the children accepting Keppra, the clearance of a levetiratsetam is increased for 22%;
• Probenetsid, streptocides, non-steroidal anti-inflammatory drugs (NPVS), methotrexate: the effect of a levetiratsetam at a concomitant use with them is unknown; reception of a probenetsid 4 times a day on 500 mg reduces renal secretion of primary metabolite;
• Peroral contraceptive (levonorgestrel and ethinylestradiol): does not change levetiratseta at reception in a dose of 1000 mg a day their pharmacokinetics;
• Warfarin and digoxin – to levetiratseta at reception in a dose of 2000 mg a day does not change their pharmacokinetics;
• Warfarin, digoxin and peroral contraceptives: do not influence pharmacokinetics of a levetiratsetam;
• Topiramat: increases risk of development of anorexia;
• Antacids: there are no data on their influence on absorption of a levetiratsetam;
• Alcohol: there are no data on interaction with levetiratsetamy.

Terms and storage conditions

To store in the place, unavailable to children, at a temperature not above 25 °C.

Period of validity – 2 years.