Levetiracetam
Levetiracetam: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Levetiracetam
ATX code: N03AX14
Active ingredient: Levetiracetam (Levetiracetam)
Producer: Drug Technology, LLC (Russia), Makiz-Pharma, LLC (Russia), Hetero Labs Limited (HETERO LABS Limited) (India)
Description and photo update: 2019-24-07
Prices in pharmacies: from 295 rubles.
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Levetiracetam is an antiepileptic drug.
Release form and composition
Levetiracetam is available in film-coated tablets. The appearance of tablets and packaging depends on the manufacturer:
- tablets with a dosage of 250 mg: oblong, film-coated blue, with a line, on one side there is an engraving "H", on the other - "87"; a white or almost white core is visible on the break of the tablet; variation in the appearance of tablets from another manufacturer - biconvex, round, with a white shell and core;
- tablets with a dosage of 500 mg: oblong, yellow film-coated, with a line, on one side there is an engraving "H", on the other - "88"; a white or almost white core is visible on the break of the tablet; variation in the appearance of tablets from another manufacturer - biconvex, oval, with a white shell and core;
- tablets with a dosage of 750 mg: oblong, film-coated orange, with a line, on one side there is an engraving "H", on the other - "90"; a white or almost white core is visible on the break of the tablet;
- tablets with a dosage of 1000 mg: oblong, film-coated white, with a line, on one side there is an engraving "H", on the other - "91"; a white or almost white core is visible on the break of the tablet; variation in the appearance of tablets from another manufacturer - biconvex, oval, with a white shell and core.
Tablets of all dosages are packed in blisters of 10 pcs., In a cardboard box of 3 or 6 blisters and instructions for the use of Levetiracetam. Possible packaging option - 30 pcs. in polymer bottles, in a cardboard box 1 bottle.
Composition for 1 film-coated tablet:
- active substance: levetiracetam - 250, 500, 750 or 1000 mg;
- auxiliary components of the tablet core: colloidal silicon dioxide, magnesium stearate, corn starch, talc, povidone K-17, croscarmellose sodium;
- film cover: for tablets with a dosage of 250 mg - Opadry II blue 85F20694 or Opadry II white 85F18422; for tablets with a dosage of 500 mg - Opadry II yellow 85F32004 or Opadry II white 85F18422; for tablets with a dosage of 750 mg - Opadry II orange 85F23452; for 1000 mg tablets - Opadry II white 85F18422.
Pharmacological properties
Pharmacodynamics
Levetiracetam is a derivative of pyrrolidone (the S-enantiomer of ethyl 2-oxo-1-pyrrolidine-acetamide). Its chemical structure differs from other known drugs for the treatment of epilepsy. The mechanism of its action is not fully understood, but it is reliably known that it differs from the mechanism of action of known antiepileptic drugs.
Studies conducted in vivo and in vitro suggest that levetiracetam does not affect normal neurotransmission and does not change the basic characteristics of neurons.
In vitro studies have shown that the drug reduces the content of calcium ions in nerve cells by weakening their current through N-type calcium channels and reducing the release of calcium from interneuronal stores. In addition, it partially mitigates the decrease in ion current through channels that are coupled with the glycine and GABA (gamma-aminobutyric acid) receptors, caused by β-carbolines and zinc.
One of the putative mechanisms of action of levetiracetam is based on binding to a synaptic vesicle membrane protein (glycoprotein SV2A), which is contained in the nerve cells of the spinal cord and the gray matter of the brain. Perhaps this is how the anticonvulsant effect of the drug is realized.
Levetiracetam prevents the development of seizures in focal (partial) seizures and in the case of generalized epileptic seizures. The main metabolite of the drug is inactive.
Pharmacokinetics
After taking the tablets inside, levetiracetam is rapidly absorbed. Its absolute bioavailability is almost 100%. The amount of absorption does not depend on food intake and dose size. In blood plasma, the maximum concentration is observed after 1.3 hours. When the drug is taken 2 times a day, an equilibrium state is achieved in two days. After a single dose of 1000 mg, the maximum plasma concentration is 31 μg / ml, after taking 1000 mg 2 times a day - 43 μg / ml.
There are no data on the distribution of the drug in the body. The connection with plasma proteins is less than 10%. The volume of distribution is approximately 0.5-0.7 l / kg (corresponds to the approximate volume of water in the human body).
Levetiracetam metabolism is negligible. The main pathway is enzymatic hydrolysis of the acetamide group (in this way, about 24% of the dose taken is biotransformed), which occurs in many tissues, including blood cells. The resulting metabolite (ucb L057) has no pharmacological activity. The amount of minor metabolites is insignificant. About 1.6% of the dose taken is transformed by hydroxylation of the pyrrolidone ring, 0.9% - by opening the pyrrolidone ring, the rest of the metabolites (less than 0.6% of the dose) have not yet been identified.
Levetiracetam and ucb L057 do not inhibit glucuronyltransferase, epoxide hydroxylase and the main isozymes of cytochrome P 450, and also do not affect the glucuronidation of valproic acid.
In adults, the half-life of the drug is 7 ± 1 hour. It does not depend on the route of administration, the dose taken or the duration of treatment. The average total clearance of levetiracetam is 0.96 ml / min / kg. More than 95% of the dose taken is excreted in the urine and less than 0.3% in the feces. During the first 48 hours, 66% of the drug and 24% of its main metabolite are excreted. Renal clearance is 0.6 and 4.2 ml / min / kg for levetiracetam and ucb L057, respectively.
In elderly patients, the half-life of the drug increases to 10-11 hours (due to decreased renal function in this age group).
In moderate to severe renal failure, it is recommended to adjust the maintenance dose depending on the level of CC (creatinine clearance). In patients with end-stage renal failure, T 1/2 is 3.1 hours during hemodialysis and 25 hours in between sessions. Within a 4-hour session, approximately 51% of the dose taken is removed.
With mild to moderate hepatic impairment, the excretion of levetiracetam remains almost unchanged. In patients with severe hepatic impairment, the clearance of the active substance is reduced by 50% or more, which is usually associated with concomitant renal impairment.
In children aged 6 to 12 years, after a single dose of Levetiracetam at a dose of 20 mg per kg of body weight, T 1/2 is 6 hours. The apparent clearance, adjusted for body weight, is 30% higher than that in adult patients with epilepsy. The absorption of the drug in children of this age category after long-term treatment in a daily dose of 20–60 mg / kg of body weight is quite fast; maximum plasma concentration is reached after 30-60 minutes; AUC (area under the concentration-time curve) and maximum plasma concentration are dose-proportional and linear. Terminal T 1/2 - 5 h, and apparent clearance - 1.1 ml / min / kg.
Indications for use
As the only agent (for monotherapy), Levetiracetam is used in patients over 16 years of age with epilepsy (if the diagnosis is established for the first time) for the treatment of partial (focal) seizures without or with secondary generalization.
In complex therapy (as an adjuvant), the drug is used to treat the following types of seizures:
- myoclonic seizures in patients with juvenile myoclonic epilepsy (in adolescents over 12 years of age and adults);
- partial (focal) seizures without or with secondary generalization in patients with epilepsy (in children over 6 years of age and in adults);
- primary generalized tonic-clonic seizures in patients with idiopathic generalized epilepsy (in persons aged 12 years and older).
Contraindications
Levetiracetam as an adjuvant is not prescribed for children under 6 years of age, as a monotherapy - under 16 years. In addition, the drug is contraindicated in patients with increased individual sensitivity to drug components or other pyrrolidone derivatives.
An antiepileptic agent is used with caution in renal failure, liver disease in the stage of decompensation and in the elderly (65 years and older).
During pregnancy, the use of Levetiracetam is possible under close medical supervision and only if there is a good reason. During lactation, taking the drug is undesirable. If there is a need for anticonvulsant therapy, the possible benefits to the mother and the potential risk to the baby, as well as the importance of maintaining breastfeeding, should be evaluated.
Levetiracetam, instructions for use: method and dosage
Levetiracetam tablets are taken orally, regardless of food, with a sufficient amount of liquid. The daily dose of the drug should be divided into two equal doses.
For adolescents over 16 years of age and adults, for the purpose of monotherapy, Levetiracetam is prescribed in an initial dose of 250 mg 2 times a day. After 2 weeks, the dose is increased to 500 mg 2 times a day. In the future, it is possible to increase the dose of the drug in increments of 250 mg 2 times a day every 2 weeks. The maximum daily dose is 3000 mg (1500 mg 2 times a day).
As an adjuvant therapy (in adults and adolescents over 12 years old with a body weight of more than 50 kg) Levetiracetam is used at an initial dose of 500 mg 2 times a day. Depending on tolerance and response to treatment, the dose can be increased or decreased in steps of 500 mg 2 times a day every 2–4 weeks. The maximum daily dose is 3000 mg (1500 mg 2 times a day).
For patients with impaired renal function, the daily dose of Levetiracetam is selected individually, taking into account the CC (these recommendations are valid for adult patients weighing more than 50 kg):
- normal renal function (CC more than 80 ml / min) - 500–1500 mg 2 times a day;
- mild renal dysfunction (CC 50–79 ml / min) - 500–1000 mg 2 times a day;
- moderate renal dysfunction (CC 30–49 ml / min) - 250–750 mg 2 times a day;
- severe renal dysfunction (CC less than 30 ml / min) - 250-500 mg 2 times a day;
- end stage renal failure (patients on hemodialysis) - 500-1000 mg once a day (on the first day - 750 mg once a day); after the hemodialysis procedure, it is recommended to take an additional 250–500 mg of the drug.
For children and adolescents (weighing less than 50 kg) with impaired renal function, the dose of Levetiracetam is adjusted as follows:
- normal renal function (CC more than 80 ml / min) - 10–30 mg / kg of body weight 2 times a day;
- mild renal dysfunction (CC 50–79 ml / min) - 10–20 mg / kg of body weight 2 times a day;
- moderate renal dysfunction (CC 30–49 ml / min) - 5–15 mg / kg of body weight 2 times a day;
- severe renal dysfunction (CC less than 30 ml / min) - 5-10 mg / kg of body weight 2 times a day;
- end-stage renal failure (patients on hemodialysis) - 10–20 mg / kg body weight once a day (on the first day - 15 mg / kg body weight once a day); after the hemodialysis procedure, it is recommended to additionally take 5-10 mg / kg of body weight.
For children, Levetiracetam is prescribed in the most convenient dosage form. The dosage depends on body weight and age. In children under 6 years of age, tablets are not used (it is recommended to use the drug in the form of an oral solution). The existing dosage of tablets is not suitable for the initial selection of the dose for children whose body weight is less than 25 kg, as well as for patients who cannot swallow tablets (in these cases, it is recommended to use levetiracetam in the form of an oral solution).
In children and adolescents under the age of 16, the safety and efficacy of the drug as a monotherapy have not been established.
The initial dose for adjuvant therapy for children aged 6 to 17 years (weighing up to 50 kg) is 10 mg / kg of body weight 2 times a day. If necessary, the dose can be increased to 30 mg / kg of body weight 2 times a day. The step of increasing or decreasing the dose is 10 mg / kg 2 times a day every 2 weeks. In children weighing more than 50 kg, the drug is used in doses prescribed for adults. It is recommended to use Levetiracetam in the lowest effective dose.
Side effects
Unwanted disorders identified in clinical trials and in the framework of post-marketing monitoring (classified as follows: very often - ≥ 1/10, often - ≥ 1/100 and <1/10, infrequently - ≥ 1/1000 and <1/100, rarely - ≥ 1/10 000 and <1/1000, very rarely - <1/10 000, including isolated cases):
- digestive system: often - dyspeptic disorders, nausea, vomiting, loose stools, abdominal pain; rarely - pancreatitis;
- hepatobiliary system: infrequently - violations of liver function tests; rarely - hepatitis, liver failure;
- metabolism and nutrition: often - anorexia; infrequently - increase or decrease in body weight;
- respiratory system: often - cough;
- lymphatic system and blood: infrequently - leukopenia, thrombocytopenia; rarely - neutropenia, pancytopenia;
- nervous system: very often - headache, drowsiness; often - dizziness, tremors, imbalance, convulsions, lethargy; infrequently - ataxia or impaired coordination of movements, attention disorder, amnesia, paresthesia, memory impairment; rarely - hyperkinesia, dyskinesia, fast and slow convulsive movements;
- mental disorders: often - aggression or hostility, nervousness, depression, irritability, sleep disturbance; infrequently - psychotic disorders, anger, emotional lability, agitation, suicidal thoughts and attempts, behavior disorder, mood changes, hallucinations, confusion; rarely - impaired thinking, personality disorder, suicide;
- sense organs: often - vertigo; infrequently - visual impairment, double vision;
- musculoskeletal system: infrequently - muscle pain, muscle weakness;
- skin and subcutaneous fat: often - rash; infrequently - itchy skin, eczema, baldness; rarely - erythema multiforme, toxic epidermal necrolysis;
- infections, invasions, trauma: very often - nasopharyngitis; infrequently - injuries; rarely - infectious diseases;
- others: often - fatigue or asthenia.
The safety profile of Levetiracetam in adults and children generally does not differ. The exception is psychiatric and behavioral side effects, which occurred more frequently in children than in adult patients (in placebo-controlled groups, the safety profile is comparable to that in adults).
Overdose
The main symptoms of a levetiracetam overdose are: anxiety, drowsiness, depression of consciousness, agitation, respiratory depression, coma.
In case of acute poisoning, it is necessary to artificially induce vomiting, rinse the stomach and give the patient activated charcoal. Further treatment is symptomatic (if necessary, the patient is sent to a hospital and hemodialysis is performed). There is no specific antidote.
special instructions
Levetiracetam should be withdrawn gradually. In adolescents and adult patients weighing more than 50 kg, it is recommended to reduce the dose in increments of 500 mg 2 times a day every 2–4 weeks; in children over 6 years of age and adolescents weighing less than 50 kg, the dose reduction step should be no more than 10 mg / kg body weight 2 times a day every 2 weeks.
During treatment with anticonvulsants (including levetiracetam), attempts at suicide, suicidal behavior and thoughts, and, in rare cases, suicide have been reported. In specially conducted controlled studies, a slight increase in the risk of suicidal behavior and thoughts has been shown, but the mechanism for realizing this risk remains unknown.
Patients with signs of depression or suicidal behavior and thoughts should be monitored and treated appropriately. Patients and their caregivers should be advised to seek medical attention if they develop symptoms of depression or suicidal thoughts.
The tablets should not be given to children under 6 years of age. The available data did not reveal any effect of the drug on puberty and growth, but the long-term effects of levetiracetam on growth, puberty, fertility, endocrine function, intelligence and learning in children are unknown.
Influence on the ability to drive vehicles and complex mechanisms
Special studies on the effect of the drug on the ability to drive vehicles and other potentially dangerous and complex mechanisms have not been conducted. Given the fact that in some patients levetiracetam can cause drowsiness, dizziness, attention disorder and impaired coordination of movements, such activities should be refrained from before determining the individual sensitivity to the drug.
Application during pregnancy and lactation
There are insufficient data on the effect of the drug on the course of pregnancy. Animal studies have shown that levetiracetam has reproductive toxicity, but how likely it is to do the same in humans is unknown.
In women of reproductive age who do not use reliable contraceptive methods, as well as pregnant women, the use of the drug is possible only if there are good reasons.
During pregnancy, the plasma concentration of levetiracetam decreases, especially in the third trimester (its value is up to 60% of the concentration characteristic of women before pregnancy). Pregnant women taking the drug should be closely monitored. With the abolition of anticonvulsant treatment, an exacerbation of the disease is possible, and this can have a negative effect on the condition of the woman and the fetus.
Levetiracetam is secreted in breast milk, therefore, taking the drug during lactation is undesirable. If anticonvulsant therapy is needed, the possible benefits to the mother and the potential risks to the baby, as well as the importance of maintaining breastfeeding, should be assessed.
Pediatric use
Monotherapy with the drug is contraindicated in children and adolescents under the age of 16 years.
As an adjuvant, Levetiracetam can be used in patients over 6 years of age.
With impaired renal function
In patients with renal impairment, Levetiracetam tablets are used with caution. The dose of the drug is adjusted depending on the QC value.
For violations of liver function
Levetiracetam is prescribed with caution to persons with liver disease in the stage of decompensation.
Use in the elderly
Elderly patients (over 65 years of age) are prescribed Levetiracetam with caution. Persons of this age category may need to adjust the dose of the drug associated with impaired renal function.
Drug interactions
The drug does not affect the serum concentrations of other anticonvulsant drugs (carbamazepine, phenobarbital, gabapentin, phenytoin, primidone, valproic acid, lamotrigine). In turn, these drugs do not affect the pharmacokinetic parameters of levetiracetam.
Probenecid in a daily dose of 2000 mg (500 mg 4 times a day) blocks tubular secretion in the kidneys, but the renal clearance of levetiracetam does not change, and only the renal clearance of the main metabolite of the drug is inhibited (nevertheless, its concentration remains low).
Levetiracetam in a daily dose of 1000 mg did not affect the hormonal status and did not change the pharmacokinetics of levonorgestrel and ethinyl estradiol; in a daily dose of 2000 mg, it did not affect the pharmacokinetic parameters of warfarin and digoxin and did not change the prothrombin time. Oral contraceptives, warfarin and digoxin also did not affect the pharmacokinetics of the drug.
The degree of absorption of levetiracetam does not change with the simultaneous intake of food, however, the absorption rate decreases slightly.
The effect of ethanol and antacids on the drug has not been studied.
Analogs
Analogues of Levetiracetam are: Zenicetam, Keppra, Levetinol, Letiram, Capaira-vero, Levetiracetam Canon, Convilept, Elsetor, Epiterra, Tirapol, Epitropil, Epikepran, Epiterra Long, etc.
Terms and conditions of storage
Keep out of the reach of children. Store at a temperature not exceeding 25 ° C.
The shelf life of the drug is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews of Levetiracetam
There are not many reviews of Levetiracetam, but in most cases they are positive. The drug is qualitatively different from other anticonvulsants and is considered one of the safest antiepileptic drugs. Side effects are rare, there are no endocrine disorders, there are no problems with excess weight, there are no apathy and depression. Patients note that Levetiracetam relieves seizures well and helps to relieve symptoms of epilepsy. Levetiracetam is sold strictly by prescription, the cost is average. One of the downsides is that anticonvulsants are not always available in pharmacies.
Price for Levetiracetam in pharmacies
The approximate prices for Levetiracetam in the form of film-coated tablets are:
- dosage 250 mg: 30 pcs. in the package - 235-305 rubles;
- dosage 500 mg: 30 pcs. in the package - 540–570 rubles, 60 pcs. in the package - 917 rubles;
- dosage 1000 mg: 30 pcs. in the package - 918-1060 rubles., 60 pcs. in the package - 1550 rubles.
Levetiracetam: prices in online pharmacies
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Drug name Price Pharmacy |
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Levetiracetam Canon 250 mg film-coated tablets 30 pcs. 295 RUB Buy |
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Levetiracetam 250 mg film-coated tablets 30 pcs. 316 RUB Buy |
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Levetiracetam Canon 500 mg film-coated tablets 30 pcs. RUB 538 Buy |
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Levetiracetam 500 mg film-coated tablets 30 pcs. RUB 668 Buy |
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Levetiracetam Canon 1000 mg film-coated tablets 30 pcs. RUB 960 Buy |
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Levetiracetam Canon 500 mg film-coated tablets 60 pcs. 997 RUB Buy |
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Levetiracetam 1000 mg film-coated tablets 30 pcs. 1188 RUB Buy |
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Levetiracetam Canon tablets p.o. 1000mg 30 pcs. 1199 RUB Buy |
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Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
