Levetral-750 Davipharm tablets treat seizures (6 blisters x 10 tablets)

Dosage form Box of 6 blisters x 10 tablets
Specifications Levetiracetam

Ingredient

Composition informationContent
Levetiracetam750mg

Uses

Indications

Levetral 750 drug indications for treatment in the following cases:

  • Single therapy in the treatment of local seizures with or without combined with the secondary epilepsy in new patients who are diagnosed with epilepsy from 16 years of age.
  • In the treatment of local seizures with or without a combination of secondary epilepsy in adults and children with epilepsy from 1 month of age and older. The whole primary.

    Pharmacological group: epilepsy medicine.

    levetiracetam, Pyrolidin derivatives, is a anti -convulsions with chemical structure that is not related to other existing epilepsy medications. The mechanism of action of levetiracetam is not known. In animals, levetiracetam does not protect against solitary seizures due to current or chemicals. The drug only protects with little stimulation below the maximum level and the threshold tests, but protecting the whole secondary convulsions after the local seizures caused by two chemicals causing seizures, there are characteristics like the complex of the whole local seizures in humans.

    Levetiracetam also has inhibition properties in the mouse model that has been reduced the stimulus threshold, similar to the person with a complex local seizure.

    levetiracetam has no affinity for benzodiazepine receptors, gamaaminobutyric acid (GABA), glycin or N-methyl d-aspartat (NMDA). The drug works through a specific location of the brain tissue, which is the 2A protein of the Synap bag (SV2A protein). This cohesion can recover, saturated and selected stereoscopic nature. Levetiracetam only attaches a localized to the Synap cell membrane in the central nervous system but is not attached to the peripheral tissue.

    levetiracetam inhibits the outbreak but does not affect normal nervous stimulation, so the selective preventive medicine is excessive synchronization of the epilepsy outbreak and the spread of epilepsy.

    pharmacokinetic

    absorption

    levetiracetam is quickly absorbed after oral use. Absolute oral bioavailability reaches nearly 100%. CMAX is achieved within 1.3 hours after drinking.

    Stable state is achieved after 2 days with a dosage mode 2 times daily. CMAX corresponding to 31 and 43 µg/ml after a single dose of 1000 mg and after the dose repeats 1000 mg twice a day.

    The level of absorption does not depend on the dose and is not affected by food.

    distribution

    There is no data distributed in tissue in humans. The cohesion ratio of levetiracetam and its initial metabolites with low plasma proteins (

    transformation

    In humans, levetiracetam does not metabolize strongly. The main metabolic path (24% of the dose) is acetamid hydrolysis with enzymes. The isomers of the liver enzyme cytochrom P450 do not participate in the process of creating main metabolites (UCB L057). The quantification of acetamid hydropicity in many tissues including blood cells. UCB L057 metabolites have no pharmacological activity.

    Two small metabolites are also determined. A substance obtained by the pyrrolidon ring hydroxy (1.6% the dose) and the remaining substance obtained by the opening of the Pyrrolidon ring (0.9% the dose).

    Other unknown metabolites accounted for only 0.6% of the dose. There is no evidence of the Invetiracetam's Invetiracetam -shaped transition or its main metabolites.

    In vitro, levetiracetam and its main metabolites do not inhibit the main isomers of the liver enzyme cytochrom P450 (CYP3A4, 2A6, 2C9, 2C19 ,, 2D6, 2E1 and 1A2), Glucurony Loverase (UGT1A1 and UGT1A6) and Epoxyd hydroxylase. In addition, levetiracetam does not affect Valproic acid glucuronylation in vitro.

    Elimination

    Selling plasma waste time in adults is 7 ± 1 hour and does not change according to the dose, sugar or repeated dose. The average body clearance is 0.96 ml/min/kg.

    The main elimination line is through the urine, accounting for the average 95% of the dose (about 93% of the dose is eliminated within 48 hours). Only 0.3% of the dosage excreted through feces.

    In the first 48 hours, the amount of excretion accumulated by Levetiracetam's urinary line and its main metabolites are 66% and 24% of the dose. The kidney clearance of levetiracetam and UCB L057 corresponding to 0.6 and 4.2 ml/min/kg shows that levetiracetam eliminates through glomerular filtration and then reabsorbing in the renal tubules and the main metabolites also excreted through active excretion in the renal tubules along with glomerular filtration. Levetiracetam elimination is correlated with creatinine clearance.

    levetiracetam is excreted through breast milk, the drug can be eliminated from the body by hemorrhage.

    Special subjects

    Elderly

    In the elderly, the sale time increases by about 40% (10 - 11 hours) due to the impaired renal function in this group.

    Patients with renal failure

    Levetiracetam's whole body clearance and its main metabolites are correlated with creatinine clearance, so the daily dosage adjustment recommends levetiracetam is based on the creatinine clearance of patients with medium and severe renal failure.

    In adults with end -stage renal failure, the sale time is about 25 hours and 3.1 hours corresponding to the break time and during dialysis. Levetiracetam segment removal ratio is 51% when performing a 4 -hour hemorrhage.

    Patients with liver failure

    In patients with mild and medium liver failure, there is no significant change in Levetiracetam clearance. In most severe patients with liver failure, the clearance of levetiracetam is reduced by more than 50% due to the attached renal failure.

    Children

    Children (from 4 to 12 years old):

  • After using a single dose (20 mg/kg) in epilepsy children (from 6 to 12 years old), Levetiracetam's disposal time is 6 hours. The calibration calibration level is about 30% higher than adults. The peak concentration of plasma is reached from 0.5 to 1 hour after drinking. The peak in plasma and the area below the linearly increased curve and proportional to the dose. Selling time is about 5 hours. The body clearance is 1.1 ml/min/kg.
  • After using a single dose (20 mg/kg) oral solution of 100 mg/ml in epilepsy children (from 1 month of age to 4 years old), levetiracetam is absorbed quickly and the peak concentration in plasma reaches about 1 hour after taken. The pharmacokinetic results show that the selling time is shorter (5.3 hours compared to 7.2 hours) and the speed of clearance is faster (1.5 ml/min/kg compared to 0.96 ml/min/kg) compared to adults. Age also affects the two parameters above. This effect is obvious in younger babies, and gradually decreases as the age increases, until the impact is not significant at about 4 years old.
  • Before taking Levetral-750 Davipharm tablets treat seizures (6 blisters x 10 tablets)

    How to use

    Levetral tablets can be taken with or not with the same meal with a sufficient amount of water.

    Dosage

    daily dose of levetiracetam should be divided into 2 use.

    Unit of treatment

    Adults and adolescents from 16 years old:

    The starting dose is 250 mg x 2 times/day and increases to 500 mg 2 times/day after 2 weeks. This dose can continue to increase by 250 mg x 2 times/day for every 2 weeks depending on the clinical response. The maximum dose is 1500 mg 2 times/day.

    combined treatment for adults (≥ 18 years old) and teenagers (from 12 to 17 years old) weighing over 50 kg. The starting dose is 500 mg 2 times/day. This dose may start from the first day of treatment.

    Based on clinical response and drug tolerance, the dose can be increased to 1500 mg 2 times/day. The willow adjustment increases or decreases to 500 mg x 2 times/ day for each period of 2 to 4 weeks.

    stop taking drugs

    If you have to stop using levetiracetam, it is recommended to stop the drug slowly (for example in adults and adolescents weighing over 50 kg: decrease 500 mg x 2 times/ day for a period of 2 to 4 weeks.

    Special subjects

    Elderly (65 years or older)

    Recommendations to adjust the dose in elderly patients with renal function damage (see the patient item of kidney failure).

    kidney failure

    Daily dose is adjusted based on kidney function.

    adjustment dose for adults and adolescents weighing more than 50kg with renal function.

    Creatinin clearance (ml/min/1.73 m2) Dosage and frequency

    Normal 0 80
    500 - 1500 mg x 2 times/day
    79
    500 - 1000 mg x 2 times/day
    The last paragraph - must be competent (1) -
    500 - 1000 mg x 1 time/day (2)

    (2): Additional dose recommends 250 - 500 mg after the appraisal.

    In children with renal failure, the dose adjustment must be based on the degree of renal failure because the levetiracetam clearance is related to kidney function. This recommendation is based on research in adult kidney failure.

    Normal group (Creatinine clearance (ml/ min/ 1.73 m2)> 80):

  • Children from 1 to 6 months of age: take dose 7 - 21 mg/kg (0.07 - 0.21 ml/kg) 2 times/day. m2) from 50 - 79):
  • Children from 1 to 6 months of age: take dose 7 - 14 mg/kg (0.07 - 0.14 ml/kg) 2 times/day. 1.73 m2) from 30 - 49):
  • Children from 1 to 6 months of age: dose 3.5 - 10.5 mg/kg (0.035 - 0.105 ml/kg) 2 times/day. minutes/ 1.73 m2)
  • Children from 1 to 6 months of age: dose 3.5 - 7 mg/kg (0.035 - 0.07 ml/kg) 2 times/day.
  • Children from 1 to 6 months of age: take dose 7 - 14 mg/kg (0.07 - 0.14 ml/kg) 1 time/day. (2) (4)
  • Children from 6 to 23 months of age, children and young people weighs less than 50kg: taking dose 10 - 20 mg/kg (0.1 - 0.2 ml/kg) 2 times/day. (3) (5)
  • (1): The oral solution should be used for less than 250 mg, the dose is not the exponential of 250 mg of recommended dose not to be achieved by taking many tablets and giving patients not swallowing tablets.

    (2): The recommended attack dose is 10.5 mg/kg (0.105 ml/kg) for the first day of treatment with levetiracetam.

    (3): The recommended attack dose is 15 mg/kg (0.15 ml/kg) for the first day of treatment with levetiracetam.

    (4): Additional doses recommend is 3.5 - 7 mg/kg (0.035 - 0.07 ml/kg) after the appraisal.

    (5): Additional dose recommends 5 - 10 mg/kg (0.05 - 0.1 ml/kg) after the appraisal.

    Hepatic failure

    No dose adjustment for patients with mild to moderate liver failure. For patients with severe liver failure, creatinine clearance may not fully assess the level of renal failure. Therefore, 50% of the daily maintenance dose should be reduced when creatinine clearance is below 60 ml/min/1.73 m2.

    Children

    Should use the most appropriate form of drugs, forms and doses based on age, weight and dose to be used.

    Tablets are not suitable for babies and children under 6 years old. The form of oral solution will be more suitable for these objects. In addition, the existing tablet dose is not suitable to start treatment in children weighing less than 25 kg, for patients to swallow tablets or indicate the dose of less than 250 mg. In all the above cases, oral solution should be used.

    Unit

    Safety and effectiveness of levetiracetam in children and adolescents under 16 years of age when used unchanged.

    Injury treatment treatments from 6 to 23 months of age, children (from 2 - 11 years old) and adolescents (from 12 - 17 years old) weighing less than 50 kg:

  • The form of oral solution will be more suitable to use for babies and children under 6 years old. The starting dose for children and adolescents is exactly 25 kg, so it is 250mg 2 times/day with a maximum dose of 750mg 2 times/day.

    Infant babies treatment from 1 to 6 months of age: It is recommended to use oral solution for babies.

    Note: The above dose is for reference only. Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.

    What to do when using overdose?

    Symptoms

    Sleep, agitation, quarrels, consciousness, respiratory failure and coma.

    Management

    If an exceeding the acute dose, the stomach can be washed or vomiting. There is no specific antidote for levetiracetam. Overdose treatment is mainly symptomatic treatment and can be clinical. Separation efficiency is 60% for levetiracetam and 74% for the first metabolites.

    What to do when forgetting 1 dose? However, if the time to relax with the next dose is too short, skip the dose and continue the calendar of the drug. Do not use double dose to compensate for missed dose.

  • Side Effects

    When using Levetral often has unwanted effects (ADR) such as:

    Very common, ADR ≥ 1/10

  • Infections and parasites: rhinitis, throat.
  • Metabolism and nutrition: Anorexia. Melting, indigestion, nausea, vomiting.
  • Blood and lymphatic system: thrombocytopenia, leukopenia. disorder/loss of air conditioning coordination, paresthesia, attention disorders. Thuong.
  • Rare, 1/10,000 ≤ ADR Infection and parasitic infection: infection. God: suicide, personality disorders, abnormal thoughts. Describe some unwanted reactions

    The risk of anorexia is higher when Levetiracetam is used with Topiramat. In many cases of hair loss, there is a recovery when stopping using Levepiracetam. There is a discovery of bone marrow inhibition in some cases of hypoglycemia.

    Children

    Levetiracetam's unwanted reactions are generally the same among age groups when used as accepted. In a placebo control clinical test, the safety of levetiracetam when used in children is similar to when used in adults except for unwanted effects on behavior and mental health more common in children.

    In a double blind test, the placebo back of Levetiracetam in children shows worse behavioral and emotional functions in Levetiracetam users. However, in the subject of long -term levetiracetam, the average behavioral and emotional function is not worse.

    Warnings

    Before using the drug you need to read the instructions carefully and refer to the information below.

    Contraindicated

    Levetral drugs are contraindicated in the following cases:

  • sensitive to levetiracetam or pyrolidon derivatives or any ingredients of the drug.
  • Precautions when used

    Do not stop the drug suddenly due to the risk of increasing the frequency of seizures. When you want to stop levetiracetam oral orally, you should stop slowly by reducing the dose 1 g every 2 weeks.

    There may be serious skin reactions in patients using levetiracetam (Stevens Johnson syndrome, poisoned epidermal necrosis). Need to stop the drug immediately and apply replacement treatments.

    Need to adjust the dose when used for patients with renal impairment due to increased risk of drug poisoning. For patients with severe liver failure, kidney function should be evaluated before starting to use the drug.

    The drug can start or worsen than the mental disorders available in patients.

    In such a case, it is necessary to reduce the dose or stop the drug and monitor patients closely. There have been reports on suicide cases, committing suicide in patients using levetiracetam.

    The drug increases the risk of suicidal thoughts or behaviors. Therefore, it is necessary to closely monitor the patient. The prescription doctor should consider the risk of suicide of the patient and the benefits of treatment with levetiracetam.

    Safety and effectiveness of the drug has not been established in children under 1 month of age suffering from local seizures, in children under 12 years old with teenage muscle vibration epilepsy or a whole epilepsy.

    There is no difference in the safety of the drug in humans aged 65 and over. However, there is not enough data to evaluate the effectiveness of the drug in this group, compared to the young group.

    levetiracetam can cause drowsiness and fatigue most common in the first 4 weeks of treatment.

    Patients should be monitored with many signs and symptoms and advise patients not to drive or operate machinery until they are sure whether they are affected or not.

    levetiracetam can cause mobility disorders. Patients should be monitored with these symptoms and symptoms and advised the patient not to drive or operate machinery until they are sure whether they are affected or not.

    levetiracetam can cause hematological disorders such as reducing the number of red blood cells, hemoglobin and hematocrit, and increasing acidic leukemia. There are also cases of reducing the number of white blood cells, neutrophils and grain leukocytes.

    In a random clinical trial, the placebo control in patients from 1 month old to

    Physiological changes during pregnancy may affect levetiracetam levels. The decrease in the concentration of levetiracetam in plasma has been observed when pregnant, especially reduced more in the last 3 months of pregnancy. It is recommended to monitor patients carefully throughout the pregnancy and continue until the special birth if there is a change in the dose during pregnancy.

    Drugs that contain polysorbat 80 can cause allergies and castor oils that can cause nausea, vomiting, abdominal pain, diarrhea.

    Used for pregnant and lactating women

    Pregnant women

    Not enough information about the use of levetiracetam in pregnant women. Except for the actual case, do not use levetiracetam for pregnant women or women of reproductive age but do not apply effective contraceptive measures.

    Physiological changes during pregnancy may affect levetiracetam levels. The decrease in plasma concentrations of levetiracetam were observed when pregnant, especially reduced more in the last 3 months of pregnancy (up to 60% of the initial concentration before pregnancy). It is necessary to ensure appropriate clinical care for pregnant women to use levetiracetam. Stop using anti -epileptic drugs can aggravate the disease and harm the mother and the fetus.

    breastfeeding women

    levetiracetam excreted through breast milk. Therefore, do not recommend using drugs for nursing women.

    Due to the risk of serious harmful events for breastfeeding, it is necessary to consider stopping the use of medication or stop breastfeeding, based on the level of necessary use for the mother.

    The effect of the drug on the ability to drive and operate machinery

    The effect of the drug on the job (operators of the machine, the driver of the train, the higher -working person and other cases): Levetiracetam has a slight or medium impact on the ability to drive or operate machinery. Due to the difference in sensitivity of each individual to the drug, some patients may be drowsy or symptoms related to other central nervous systems, especially when they start treatment or after increasing dose.

    Therefore, patients with the above symptoms should be cautious when driving or operating machinery. It is recommended that patients do not drive or operate machinery until determining that the drug does not affect the ability to perform those activities.

    Drug interaction

    Other anti -epileptic drugs

    Clinical research conducted in adults shows that Levetiracetam does not affect the serum concentration of anti -epileptic drugs in use (phenytoin, carbamazepine, valproic acid, phenobarbital, lamotrigin, gabapentin and primidons) and these drugs do not affect the pharmacokinetics of levetiracetam.

    As in adults, there is no evidence of any significant drug interaction in children using levetiracetam doses to 60 mg/kg/day.

    A rescue assessment of pharmacokinetic interaction in children and adolescents with epilepsy (from 4 - 17 years old) confirmed that treatment in combination with levetiracetam used oral route does not affect serum concentration in the stable state of carbamazepine and valproot when used simultaneously.

    However, data suggests that Levetiracetam clearance increases 20% in children using anti -epileptic drugs. No need to adjust willow.

    Probenecid

    Probenecid (500 mg 4 times/day), drugs that prevent the renal tubules, inhibit the elimination in the kidneys of the main metabolic substance, but do not inhibit the elimination of levetiracetam.

    However, the concentration of this metabolite is low.

    methotrexate

    There has been a report on the reduction of the clearance of methotrexate when used simultaneously with levetiracetam, resulting in increasing the concentration/extending the existence time of methotrexate in the blood to toxicity.

    concentration of methotrexate and levetiracetam in the blood should be carefully monitored in patients using 2 drugs simultaneously.

    Oral contraceptives and other pharmacological interactions

    Levetiracetam 1000 mg daily does not affect the pharmacokinetics of oral contraceptives (ethinylestradiol and levonorgestrel); Endocrine parameters (hormones create physical and progesterone) are not changed. Levetiracetam 2000 mg daily does not affect pharmacokinetics of digoxin and warfarin; Prothrombin time is not changed. Using Digoxin, oral contraceptives and warfarin does not affect the pharmacokinetics of levetiracetam.

    laxatives

    There are single reports on levetiracetam's effectiveness when used with macrogol osmotic laxatives when used simultaneously two drugs. Therefore, macrogol should not be taken for about 1 hour before and after taking levetiracetam.

    Food and wine

    Levetiracetam's absorption level is not changed by food, but the absorption speed is slightly reduced.

    There is no information on levetiracetam's interaction with alcohol.

    Storage

    Leave a cool place, avoid light, temperature below 30⁰C.

    To be out of reach of children.

    Other drugs

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