Keppra - instructions for use, analogs, reviews and release forms (tablets 250 mg, 500 mg and 1000 mg, injections in injectable vials and droppers, solution or syrup) drugs for the treatment of epilepsy in adults, children and pregnancy. Composition

In this article, you can read the instructions for using the drug Keppra. Presented are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors of specialists on the use of Keppra in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Koppra in the presence of existing structural analogs. Use to treat epilepsy and arrest seizures and seizures in adults, children, as well as during pregnancy and lactation. Composition of the preparation.

 

Keppra - antiepileptic drug, pyrrolidone derivative (S-enantiomer alpha-ethyl-2-oxo-1-pyrrolidine-acetamide), differs in chemical structure from known antiepileptic drugs. The mechanism of action of levetiracetam (the active substance of the drug Keppra) is not fully understood, but it is clear that it differs from the mechanism of action of known antiepileptic drugs.

 

Studies have shown that Keppra affects the intra-neuronal concentration of Ca ions, partially inhibiting the Ca current through N-type channels and reducing the release of calcium from intra-neuronal depots. In addition, levetiracetam partially restores the currents through GABA- and glycine-dependent channels, reduced by zinc and beta-carbolines.

 

One of the proposed mechanisms is based on proven binding to the glycoprotein of the synaptic SV2A vesicles contained in the gray matter of the brain and spinal cord. It is believed that the anticonvulsant effect is realized in this way, which is expressed in counteracting the hypersynchronization of neuronal activity. Does not change the normal neurotransmission, but suppresses epileptiform neuronal outbreaks induced by GABA agonist bicuculine, and the excitation of glutamate receptors.The activity of the drug has been confirmed with respect to both focal and generalized epileptic seizures (epileptiform manifestations / photoparoxysmal reaction).

 

Composition

 

Levetiracetam + excipients.

 

Pharmacokinetics

 

After oral administration, levetiracetam is well absorbed from the digestive tract. Absorption is complete and linear, so the concentration in the blood plasma can be predicted based on the applied dose of the drug in mg / kg body weight. The degree of absorption is independent of the dose and time of ingestion. Bioavailability is about 100%. The equilibrium state is achieved after 2 days with a two-time intake of the drug. The binding to plasma proteins of levetiracetam and its main metabolite is less than 10%. The formation of the primary pharmacologically inactive metabolite (ucb L057) occurs without the participation of cytochrome P450 isoenzymes in the liver. Levetiracetam does not affect the enzymatic activity of hepatocytes. 95% of the dose is excreted by the kidneys.

 

Pharmacokinetics in special clinical cases

 

In elderly patients, the half-life increases by 40% and is 10-11 hours, which is associated with a decrease in kidney function in this category of people.

 

In the course of 4-hour dialysis, 51% of levetiracetam is removed from the body.

 

In patients with mild and moderate violations of liver function, significant changes in the clearance of levetiracetam do not occur. In severe violations of liver function with concomitant renal failure, the clearance of levetiracetam decreases by more than 50%.

 

The pharmacokinetics of levetiracetam in children is linear in the dose range from 20 to 60 mg / kg per day. The total clearance of levetiracetam in children is approximately 40% higher than in adults and is directly related to body weight.

 

Indications

 

As a monotherapy (the drug of the first choice) in the treatment:

• partial seizures with secondary generalization or without it in adults and adolescents over 16 years old with newly diagnosed epilepsy.

 

As part of complex therapy in the treatment of:

• partial seizures with secondary generalization or without it in adults and children older than 4 years with epilepsy (for tablets);
• partial seizures with secondary generalization or without it in adults and children older than 1 month suffering from epilepsy (for solution);
• myoclonic seizures in adults and adolescents over 12 years with juvenile myoclonic epilepsy;
• primary-generalized convulsive (tonic-clonic) seizures in adults and adolescents over 12 years with idiopathic generalized epilepsy.

 

Forms of release

 

Tablets, film-coated 250 mg, 500 mg and 1000 mg.

 

Concentrate for the preparation of a solution for infusions (injections in ampoules for injections and droppers).

 

Solution for oral administration (sometimes mistakenly called syrup).

 

Instructions for use and dosage

 

Tablets and oral solution

 

The daily dose is divided into 2 identical doses.

 

Monotherapy

 

Adults and adolescents over 16 years of age the drug is prescribed in the form of tablets or oral solution in an initial dose of 500 mg divided into 2 divided doses (250 mg twice a day). After 2 weeks, the dose may be increased to the initial therapeutic dose - 1 g (500 mg twice a day). The maximum daily dose is 3 g (1.5 g twice a day).

 

As part of complex therapy

 

Children aged from 1 month to 6 months of the drug is prescribed in the form of a solution for oral administration. The initial treatment dose is 7 mg / kg 2 times a day. Depending on the clinical efficacy and tolerability, the dose can be increased to 21 mg / kg 2 times per day.The dose change should not exceed plus or minus 7 mg / kg 2 times a day every 2 weeks. The minimum effective dose should be given.

 

In children aged 6 months to 23 months, children aged 2 to 11 years and adolescents from 12 to 17 years with a body weight of less than 50 kg, treatment should begin with a dose of 10 mg / kg body weight divided into 2 divided doses (10 mg / kg body weight 2 times a day). Depending on the clinical response and the tolerability of the drug, the daily dose can be increased to 30 mg / kg 2 times a day. A dose change of 10 mg / kg body weight can be done every 2 weeks. The minimum effective dose should be used.

 

Doses for children weighing 50 kg or more are the same as for adults.

 

In children older than 4 years, treatment should begin with a daily dose of 20 mg / kg body weight divided into 2 doses (10 mg / kg body weight 2 times a day). A dose change of 20 mg / kg body weight can be performed every 2 weeks until the recommended daily dose is 60 mg / kg body weight (30 mg / kg body weight 2 times a day). With intolerance of the recommended daily dose, it is possible to reduce it. The minimum effective dose should be used.

 

Prescribe the drug in the most appropriate dosage form and dose, depending on the patient's body weight and the required therapeutic dose.

 

Children with body weight less than 20 kg are advised to begin treatment with taking the drug in the form of a solution for oral administration.

 

Children with a body weight of more than 50 kg are dosed according to the scheme given for adults.

 

Adults and adolescents over 16 years of age with a body weight of more than 50 kg should be treated with a daily dose of 1 g divided into 2 divided doses (500 mg twice a day). Depending on the clinical response and the tolerability of the drug, the daily dose can be increased to a maximum of 3 g (1.5 g twice daily). A dose change of 500 mg 2 times a day can be carried out every 2-4 weeks.

 

Since levetiracetam is excreted by the kidneys when the drug is administered to elderly patients and patients with renal insufficiency, the dose should be adjusted depending on the magnitude of the CC.

 

QA can be calculated from the serum creatinine concentration, according to the following formula:

• For men, CK (ml / min) = [140-years (years)] × body weight (kg) / 72 × serum creatinine (mg / dL).
• For women, the value obtained is x 0.85.

 

Children with renal insufficiency correction of the dose of levetiracetam should be made taking into account the degree of renal failure, using recommendations given for adults.

 

Patients with impaired liver function of mild to moderate severity do not need to adjust the dosage regimen. In patients with decompensated hepatic impairment and renal insufficiency, the value of QA may not reflect the true extent of renal dysfunction, so a QC of less than 70 ml / min is recommended to reduce the daily dose by 50%.

 

Application rules

 

Tablets should be taken orally, with a sufficient amount of liquid, regardless of food intake.

 

Dosage of the solution is carried out using a measuring syringe with a nominal capacity of 10 ml (corresponding to 1 g of levetiracetam) and with a 25 mg dividend (corresponding to 0.25 ml) supplied with the preparation. The metered dose of the drug is diluted in a glass of water (200 ml).

 

To dispense the solution with a syringe, you need to open the bottle: to do this, press the cap and turn it counter-clockwise. Insert the syringe adapter into the neck of the vial, then take the syringe and place it in the adapter.Turn the bottle upside down. Fill the syringe with a small amount of solution, pulling the piston down, then push the plunger upward to remove air bubbles. Pulling the plunger, fill the syringe with the solution until it divides, corresponding to the number of ml of the solution prescribed by the doctor. Remove the syringe from the adapter. The contents of the syringe enter into a glass with water, pushing the piston to the stop. You should drink completely the entire contents of the glass. Then rinse the syringe with water and close the bottle with a plastic lid.

 

Ampoules for injections and droppers

 

The drug is administered as an infusion.

 

The transition from oral to intravenous administration and back can be carried out with preservation of the dose and the frequency of administration. One vial of concentrate for solution for infusion contains 500 mg of levetiracetam (100 mg / ml).

 

The daily dose is divided into two injections in the same dose.

 

Before use, the concentrate must be diluted with a solvent of at least 100 ml. Enter in / in the drip (in the form of droppers) for 15 minutes.

 

As solvents can be used: 0.9% solution of sodium chloride for injection; Ringer's lactate solution for injection; 5% Dextrose solution for injection.

 

The solution retains chemical stability at a temperature of 15-25 degrees Celsius for 24 hours in polyvinyl chloride packages. However, from the point of view of microbiological purity, the drug should be used immediately after dilution.

 

If necessary, storage of the solution at a temperature of 2 to 8 degrees Celsius is allowed for 24 hours provided that the dilution was carried out under aseptic conditions. In this case, the responsibility for microbiological purity lies with the user.

 

Monotherapy

 

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

 

As part of complex therapy

 

Children from 4 to 11 years and adolescents 12-17 years old with a body weight of up to 50 kg should begin treatment with a daily dose of 20 mg / kg body weight divided into 2 injections (10 mg / kg body weight 2 times a day). A dose change of 10 mg / kg body weight can be performed every 2 weeks until the recommended daily dose is 60 mg / kg body weight (30 mg / kg body weight 2 times a day).With intolerance of the recommended daily dose, it is possible to reduce it.

 

The minimum effective dose should be used.

 

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

 

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

 

The creatinine clearance for men can be calculated based on the serum creatinine concentration, according to the following formula: CK (ml / min) = [140 - age (years)] × body weight (kg) / 72 × CC (mg / dL) .

 

The creatinine clearance for women can be calculated by multiplying the obtained value by a factor of 0.85.

 

Children with renal insufficiency correction of the dose of levetiracetam should be made taking into account the degree of renal failure, using recommendations given for adults.

 

Patients with a malfunction of the liver of mild and moderate severity of the correction of the dosing regimen is not required. In patients with decompensated impairment of liver function and renal failure, a decrease in creatinine clearance may not fully reflect the severity of renal failure. In such cases, when creatinine clearance is less than 60 ml / min / 1.73 m2, a daily dose reduction of 50% is recommended.

 

The duration of the course of treatment is determined by the doctor.

 

Side effect

• drowsiness;
• asthenic syndrome;
• amnesia;
• ataxia;
• convulsions;
• dizziness;
• headache;
• hyperkinesia;
• tremor;
• disturbance of balance;
• decreased concentration of attention;
• memory impairment;
• excitation;
• depression;
• emotional lability;
• changeability of mood;
• hostility / aggressiveness;
• insomnia;
• nervousness;
• irritability;
• personality disorders;
• violation of thinking;
• paresthesia;
• behavioral disorders;
• anxiety;
• anxiety;
• confusion of consciousness;
• hallucinations;
• irritability;
• psychotic disorders;
• suicide, suicide attempts and suicidal intentions;
• diplopia;
• violation of accommodation;
• increased cough;
• abdominal pain;
• diarrhea;
• dyspepsia;
• nausea, vomiting;
• anorexia;
• weight gain, weight loss;
• pancreatitis;
• liver failure;
• hepatitis;
• changes in functional liver samples;
• skin rash;
• eczema, itching;
• alopecia (in some cases, the restoration of the hair was observed after the drug was withdrawn);
• Stevens-Johnson syndrome;
• erythema multiforme;
• toxic epidermal necrolysis;
• leukopenia, neutropenia, pancytopenia (in some cases with oppression of bone marrow function), thrombocytopenia;
• infection;
• vertigo;
• nasopharyngitis;
• myalgia.

 

Contraindications

• children under 4 years of age (for tablets and injections or droppers) (safety and efficacy of the drug are not established);
• Children's age up to 1 month (for solution) (safety and efficacy of the drug are not established);
• impaired tolerance to fructose (for solution);
• hypersensitivity to levetiracetam or other pyrrolidone derivatives, as well as to any components of the drug.

 

Application in pregnancy and lactation

 

Adequate and strictly controlled clinical studies on the safety of the use of Keppra in pregnant women have not been conducted. Studies in animals have revealed reproductive toxicity.Therefore, the drug should not be administered during pregnancy, except in cases of extreme necessity.

 

Physiological changes in the body of a woman during pregnancy can affect the plasma concentration of levetiracetam, as well as other antiepileptic drugs. During pregnancy, there was a decrease in the concentration of levetiracetam in plasma. This decrease is more pronounced in 1 trimester (up to 60% of the baseline concentration in the period preceding the pregnancy). Treatment of pregnant women should be carried out under special control. Interruptions in antiepileptic therapy may lead to a worsening of the course of the disease, which can harm the health of both the mother and the fetus.

 

Keppra is excreted in breast milk, therefore, if it is necessary to use it during lactation, breastfeeding when taking the drug is not recommended. However, if treatment with levetiracetam is necessary during the feeding period, the risk ratio for the child and the benefit of the treatment for the mother should be carefully weighed against the importance of feeding.

 

Use in children

 

Contraindicated in children under 4 years of age (for tablets and injections or droppers) (safety and efficacy not established).

 

Contraindicated in children under 1 month of age (for solution) (safety and efficacy of the drug are not established).

 

The available information on the use of the drug in children does not indicate any of its negative effects on development and puberty. However, the long-term consequences of treatment on the ability of children to learn, their intellectual development, growth, endocrine gland functions, sexual development and fertility remain unknown.

 

Application in elderly patients

 

With caution should prescribe the drug to elderly patients (over 65 years).

 

special instructions

 

If you want to stop taking the drug, then it is recommended to cancel cancellation gradually, reducing the single dose by 500 mg every 2-4 weeks. In children, the dose reduction should not exceed 10 mg / kg of body weight 2 times a day every 2 weeks.

 

Concomitant antiepileptic drugs (during the transfer of patients to receive levetiracetam) should be gradually phased out.

 

Patients with kidney disease and decompensated liver disease are recommended to study the function of the kidneys before treatment. If the kidney function is impaired, a dose adjustment may be required.

 

Due to reports of cases of suicide, suicidal intentions and suicide attempts in the treatment with levetiracetam, patients should be warned to immediately notify the attending physician of any symptoms of depression or suicidal intentions.

 

The solution for oral ingestion contains maltitol, therefore, in patients with impaired tolerance to fructose, taking Keppra in the appropriate dosage form is contraindicated.

 

The drug contains 0.83 mmol (or 19 mg) of sodium per ampoule. This should be taken into account for patients on a diet with sodium restriction.

 

Clinical experience of infusion application of levetiracetam in the period exceeding 4 days is absent.

 

Do not use the drug when changing the color of the solution or the appearance of mechanical inclusions.

 

Impact on the ability to drive vehicles and manage mechanisms

 

The effect of Keppra's preparation on the ability to drive vehicles and control mechanisms has not been specifically studied. Nevertheless, due to the different individual sensitivity to the drug from the side of the central nervous system during the treatment period, it is necessary to refrain from driving motor vehicles and practicing potentiallydangerous activities that require increased concentration and speed of psychomotor reactions.

 

Drug Interactions

 

Keppra does not interact with anticonvulsant drugs (phenytoin, carbamazepine, valproic acid, phenobarbital, lamotrigine, Gabapentin and primidone).

 

Keppra in a daily dose of 1 g does not change the pharmacokinetics of oral contraceptives (ethinyl estradiol and levonorgestrel).

 

Keppra in a daily dose of 2 g does not change the pharmacokinetics of Warfarin and digoxin.

 

Digoxin, oral contraceptives and warfarin do not affect the pharmacokinetics of levetiracetam.

 

With joint admission with topiramate, the probability of anorexia is higher.

 

Completeness of absorption of levetiracetam does not change under the influence of food, while the rate of absorption is somewhat reduced.

 

Data on the interaction of Keppra with alcohol are absent.

 

Analogues of the drug Keppra

 

Structural analogs for the active substance:

• Levetinol;
• Epitera;
• Levetiracetam;
• Epikepran;
• Lethiram;
• Comwiron;
• Thirapol;
• Epitropyl;
• Zenicetam;
• Kepyra faith;
• Epitera;
• Epiterra Long;
• Elator.

 

Analogues on the curative effect (remedies for the treatment of epilepsy):

• Algerian;
• Acetazolamide;
• Benzobarbital;
• Valparin;
• Valproate sodium;
• Valproic acid;
• Gabagamma;
• Gabapentin;
• Halodiff;
• Gapentec;
• Hexamidine;
• Depakin;
• Depakin chrono;
• Depakin Chronosphere;
• Diazepam;
• Diakarb;
• Dipromal;
• Diphenine;
• Zagreton;
• Zenicetam;
• Zeptol;
• Zonegran;
• Inovevelon;
• Carbaleptin retard;
• Carbamazepine;
• Carbasan retard;
• Caten;
• Clonazepam;
• Convalis;
• Convulex;
• Convulsant;
• Lamitor;
• Lamotrigine;
• Levetiracetam;
• Lyrics;
• Mazepine;
• Maxitope;
• Neuronthin;
• Pregabalin;
• Prigabilon;
• Relium;
• Replica;
• Rivotril;
• Ropimat;
• Sabril;
• Sibazon;
• Storilate;
• Suxilep;
• Tebantin;
• Topalepsin;
• Topamax;
• Topiramate;
• Topiromax;
• Phenobarbital (Luminal);
• Fimazepsin;
• Finlepsin;
• Finlepsin retard;
• Chloracon;
• Egipentin;
• Enkorat;
• Epimax;
• Eplorontin.

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