Keppra 500mg N30 coated pills
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Active ingredients
Levetiracetam
Release form
Pills
Composition
1 tablet contains: levetiracetam dihydrochloride 500 mg. Auxiliary substances: croscarmellose sodium, macrogol 6000, silicon dioxide, magnesium stearate. The composition of the film shell: opadry 85F32004 (dye of iron oxide yellow oxide (E172), macrogol 3350, polyvinyl alcohol partially hydrolyzed. dioxide (E171)).
Pharmacological effect
The antiepileptic drug, a pyrrolidone derivative (S-enantiomer of α-ethyl-2-oxo-1-pyrrolidine-acetamide), differs in its chemical structure from the known antiepileptic drugs. The mechanism of action of levetiracetam is not fully understood, but it is obvious that it differs from the mechanism of action of known antiepileptic drugs. In vitro studies have shown that levetiracetam affects the intraneuronal concentration of Ca2 + ions, partially inhibiting Ca2 + current through N-type channels and reducing the release of calcium from intraneuronal depot In addition, levetiracetam partially restores currents through GABA- and glycine-dependent channels, reduced by zinc and β-carbolines. One of the alleged mechanisms is based on the proven binding of the synaptic vesicle SV2A to the glycoprotein contained in the gray matter of the brain and spinal cord. It is believed that in this way the anticonvulsant effect is realized, which is expressed in counteracting the hypersynchronization of neural activity. Does not alter normal neurotransmission, however, suppresses epileptiform neuronal outbursts induced by a GABA agonist biculin and stimulation of glutamate receptors. The activity of the drug is confirmed in relation to both focal and generalized epileptic seizures (epileptiform manifestations / photoparoxysmal reaction).
Pharmacokinetics
AbsorptionAfter ingestion, levetiracetam is well absorbed from the gastrointestinal tract. Absorption is complete and linear, therefore plasma concentration can be predicted on the basis of the applied dose of the drug in mg / kg body weight. The degree of absorption does not depend on the dose and time of eating. Bioavailability is about 100%. After taking the drug in a dose of 1 g Cmax in the blood plasma is reached after 1.3 hours and is 31 μg / ml, after repeated administration (2 times / day) - 43 μg / ml. The distribution of the equilibrium state is reached after 2 days at twice taking the drug. Binding to plasma proteins of levetiracetam and its main metabolite is less than 10%.Vd of levetiracetam is about 0.5-0.7 l / kg. MetabolismThe 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. The release of adult T1 / 2 from blood plasma is 7 ± 1 h and does not change depending on the dose, the route of administration or the repeated administration. The average clearance is 0.96 ml / min / kg. 95% of the dose is excreted by the kidneys. The renal clearance of levetiracetam and its inactive metabolite is 0.6 ml / min / kg and 4.2 ml / min / kg, respectively. Pharmacokinetics in special clinical situations in elderly patients T1 / 2 increases by 40% and is 10-11 hours, which is associated with a decrease in renal function in this category of people. In patients with impaired renal function, the clearance of levetiracetam and its primary metabolite correlates with creatinine clearance. Therefore, patients with renal insufficiency are recommended to select the dose depending on the CC. In the terminal stage of renal failure in adult patients T1 / 2 is 25 hours during the period between dialysis sessions and 3.1 hours during dialysis. During the 4-hour dialysis session, up to 51% of levetiracetam is removed. During the 4-hour dialysis, 51% of levetiracetam is removed from the body. In patients with mild and moderate hepatic impairment, no significant changes in the clearance of levetiracetam occur. With severe violations of liver function with concomitant renal failure, the clearance of levetiracetam is reduced by more than 50%. The pharmacokinetics of levetiracetam in children is linear in the dose range from 20 to 60 mg / kg / day. Cmax is achieved in 0.5–1 h. T1 / 2 in children after a single oral administration at a dose of 20 mg / kg body weight is 5–6 h. The total clearance of levetiracetam in children is about 40% higher than in adults and is directly dependent from body weight.
Indications
As a monotherapy (drug of first choice) in the treatment of: - 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 for treatment: - partial seizures with secondary generalization or without adults and children older than 4 years old, suffering from epilepsy (for pills); - partial seizures with or without secondary generalization in adults and children older than 1 month,suffering from epilepsy (for solution); - myoclonic convulsions in adults and adolescents over 12 years old with juvenile myoclonic epilepsy; - primary generalized convulsive (tonic-clonic) seizures in adults and adolescents over 12 years of age with idiopathic generalized epilepsy.
Contraindications
- children's age up to 4 years (for pills) (safety and efficacy of the drug have not been established); - children up to 1 month (for solution) (safety and efficacy of the drug have not been established); - violation of fructose tolerance (for solution); - increased sensitivity to components of the drug; - hypersensitivity to other pyrrolidone derivatives. With caution, the drug should be prescribed to elderly patients (over 65), with liver disease in the stage of decompensation, renal failure.
Use during pregnancy and lactation
Adequate and strictly controlled clinical studies on the safety of levetiracetam in pregnant women have not been conducted, so the drug should not be prescribed during pregnancy, except in cases of extreme necessity. Physiological changes in the woman's body during pregnancy can affect the plasma concentration of levetiracetam, as well as and other antiepileptic drugs. During pregnancy, a decrease in plasma concentration of levetiracetam was observed. This decrease is more pronounced in the first trimester (up to 60% of the baseline concentration in the period preceding the pregnancy). The treatment of pregnant women with levetiracetam should be carried out under special control. It should be borne in mind that interruptions in antiepileptic therapy may worsen the course of the disease, which is harmful for both the mother and the fetus. Levetiracetam is excreted in breast milk, so breastfeeding is not recommended for drug treatment. However, if treatment with levetiracetam is necessary during lactation, then the risk / benefit ratio of treatment should be carefully weighed against the importance of breastfeeding.
Dosage and administration
The daily dose is divided into 2 identical doses. Monotherapy The adults and adolescents over 16 years old are prescribed the drug in the form of pills or oral solution in the initial dose of 500 mg divided into 2 doses (250 mg 2 times / day).After 2 weeks, the dose can be increased to the initial therapeutic dose - 1 g (500 mg 2 times / day). The maximum daily dose is 3 g (1.5 g 2 times / day). As part of complex therapy for children aged 1 month to 6 months, the drug is prescribed in the form of an oral solution. The initial therapeutic dose is 7 mg / kg 2 times / day. Depending on the clinical efficacy and tolerability, the dose may be increased to 21 mg / kg 2 times / day. The dose change should not exceed plus or minus 7 mg / kg 2 times / day every 2 weeks. The minimum effective dose should be prescribed. In children aged 6 months to 23 months, children aged 2 years to 11 years and adolescents from 12 years to 17 years old with a body weight less than 50 kg, treatment should be started with a dose of 10 mg / kg mass body, divided into 2 doses (10 mg / kg body weight 2 times / day). Depending on the clinical response and tolerability of the drug, the daily dose may be increased to 30 mg / kg 2 times / day. A dose change of 10 mg / kg body weight can be administered every 2 weeks. The minimum effective dose should be applied. Doses for children weighing 50 kg or more are the same as for adults. Children over 4 years of age should begin treatment with a daily dose of 20 mg / kg body weight divided into 2 doses (10 mg each). / kg body weight 2 times / day). A dose change of 20 mg / kg body weight can be carried out every 2 weeks until the recommended daily dose is reached - 60 mg / kg body weight (30 mg / kg body weight 2 times / day). In case of intolerance to the recommended daily dose, its reduction is possible. The minimum effective dose should be applied. The drug should be given in the most appropriate dosage form and dose, depending on the patient's body weight and the required therapeutic dose. Children with a body weight of ≤ 20 kg are advised to start treatment with the drug in the form of oral solution. body> 50 kg dosing is carried out according to the scheme given for adults. Adults and adolescents over 16 years old with a body weight of more than 50 kg should begin treatment with a daily dose of 1 g divided into 2 doses (500 mg 2 times / day). Depending on the clinical response and tolerability of the drug, the daily dose may be increased to a maximum of 3 g (1.5 g, 2 times a day). A dose change of 500 mg 2 times / day can be carried out every 2-4 weeks. Because levetiracetam is eliminated by the kidneys when prescribing the drug to elderly patients and patients with renal insufficiency, the dose should be adjusted depending on the size of CK. Levetiracetam dose adjustment should be made taking into account the degree of renal failure using recommendationsdata for adults. For patients with mild and moderately impaired liver function, dosing regimen adjustment is not required. In patients with decompensated liver dysfunction and renal insufficiency, the CC value may not reflect the true degree of renal dysfunction, therefore, for CC <70 ml / min, a 50% reduction in daily dose is recommended. Tablets should be ingested with enough liquid, regardless from food intake. Dosing 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 dividing price of 25 mg (corresponding to 0.25 ml), included delivery of the drug. A measured dose of the drug is diluted in a glass of water (200 ml). To dispense the solution using a measuring syringe, open the bottle: to do this, press the cap and turn it counterclockwise. Insert the syringe adapter into the neck of the bottle, then take the syringe and place it into the adapter. Turn the bottle upside down. Fill the syringe with a small amount of solution by pulling the plunger down, then push the plunger up to remove air bubbles. Pulling the plunger, fill the syringe with a solution before dividing, corresponding to the amount of ml of solution prescribed by the doctor. Pull the syringe out of the adapter. Enter the contents of the syringe into a glass of water, pushing the piston until it stops. You should drink all the contents of the glass. Then rinse the syringe with water and close the bottle with a plastic cap.
Side effects
Possible side effects are listed below in the body systems and frequency of occurrence: very often (> 1/10), often (> 1/100, <1/10). From the CNS: very often - drowsiness, asthenic syndrome; often - amnesia, ataxia, convulsions, dizziness, headache, hyperkinesia, tremor, balance disorder, loss of concentration, memory loss, agitation, depression, emotional lability, mood swings, hostility / aggressiveness, insomnia, nervousness, irritability, personality disorders, disturbed thinking; in some cases - paresthesias, behavioral disorders, anxiety, anxiety, confusion, hallucinations, irritability, psychotic disorders, suicide,attempts of suicide and suicidal intent. On the part of the organ of vision: often - diplopia, disturbance of accommodation. On the part of the respiratory system: often - increased cough. On the part of the digestive system: often - abdominal pain, diarrhea, dyspepsia, nausea, vomiting, anorexia, weight gain bodies; in some cases - pancreatitis, liver failure, hepatitis, changes in liver function tests, weight loss. Dermatological reactions: often - skin rash, eczema, itching; in some cases - alopecia (in some cases, hair restoration was observed after discontinuation of the drug), Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis. From the hematopoietic system: in some cases - leukopenia, neutropenia, pancytopenia (in some cases with inhibition bone marrow function), thrombocytopenia. Other: in some cases - infections, nasopharyngitis, myalgia.
Overdose
Symptoms: drowsiness, anxiety, aggressiveness, depression of consciousness, respiratory depression, coma. Treatment: in the acute period - an artificial challenge of vomiting and gastric lavage followed by the appointment of activated carbon. There is no specific antidote for levetiracetam. If necessary, symptomatic treatment is carried out in a hospital using hemodialysis (dialysis is 60% effective for levetiracetam, 74% for its primary metabolite).
Interaction with other drugs
Leveetera does not interact and digoxin. Digoxin, oral contraceptives and warfarin do not affect the pharmacokinetics of levetiracetam. When used together with topiramate, anorexia is more likely to develop. The extent of absorption of levetiracetam does not change under the influence of food, while the rate of absorption somewhat decreases. There are no data on the interaction of levetiracetam with alcohol.
special instructions
If you want to stop taking the drug, it is recommended to cancel, gradually, reducing a single dose of 500 mg every 2-4 weeks. In children, the dose reduction should not exceed 10 mg / kg of body weight 2 times / day every 2 weeks. It is advisable to abolish concomitant antiepileptic drugs (during the transfer of patients to levetiracetam) gradually. Renal function testing is recommended for patients with kidney disease and decompensated liver diseases before starting treatment. If kidney function is impaired, a dose adjustment may be required. Due to reports of suicide cases, suicidal intentions and suicide attempts during treatment with levetiracetam, patients should be warned to immediately report any symptoms of depression or suicidal intentions to their doctor. The oral solution contains maltitol therefore, patients with impaired fructose tolerance are taking Keppra; in the appropriate dosage form is contraindicated. Use in pediatrics The available information about the use of the drug in children does not indicate any of its negative effects on development and puberty. However, the long-term effects of treatment on children's ability to learn, their intellectual development, growth, endocrine gland functions, sexual development and fertility remain unknown. Effects on the ability to drive vehicles and control mechanisms The effect of Keppra; on the ability to drive vehicles and control mechanisms has not been specifically studied. However, due to the varying individual sensitivity to the drug on the part of the central nervous system during the period of treatment, it is necessary to refrain from driving vehicles and practicing potentially hazardous activities that require high concentration of attention and quickness of psychomotor reactions.