Keppra Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

Uses

Levetiracetam is used to treat seizures (epilepsy). It belongs to a class of drugs known as anticonvulsants. Levetiracetam may decrease the number of seizures you have.

How to use Keppra

Read the Medication Guide and, if available, the Patient Information Leaflet provided by your pharmacist before you start taking levetiracetam and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take the liquid and regular-release tablets by mouth as directed by your doctor, usually twice daily with or without food. Crushing or chewing the tablet may cause a bitter taste.

If you are using the liquid form of this medication, carefully measure the dose using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose.

If you are using the extended-release tablets, take this medication as directed by your doctor, usually once daily. Swallow the extended-release tablets whole. Do not crush or chew the tablets. Doing so can release all of the drug at once, increasing the risk of side effects.

The dosage is based on your medical condition and response to treatment. The dosage in children is also based on weight. To reduce your risk of side effects (such as dizziness and drowsiness), your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor’s instructions carefully.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.

Do not increase your dose or use this drug more often or for longer than prescribed. Your condition will not improve any faster, and your risk of side effects will increase.

Do not stop taking this medication without consulting your doctor. Your seizures may become worse when the drug is suddenly stopped. Your dose should be gradually decreased.

Tell your doctor if your seizures lasts, change, or gets worse.

Side Effects

Drowsiness, dizziness, unusual tiredness, or weakness may occur. These side effects are more common during the first 4 weeks and usually lessen as your body adjusts to the medication. If any of these effects last or get worse, tell your doctor or pharmacist promptly.

Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, such as: loss of coordination (such as difficulty walking and controlling muscles), mental/mood changes (such as irritability, aggression, agitation, anger, anxiety), signs of infection (such as sore throat that doesn’t go away, fever, chills), signs of anemia (such as unusual tiredness that doesn’t go away, pale skin, fast breathing, fast heartbeat), easy bruising/bleeding.

A small number of people who take anticonvulsants for any condition (such as seizures, bipolar disorder, pain) may experience depression, suicidal thoughts/attempts, or other mental/mood problems. Tell your doctor right away if you or your family/caregiver notice any unusual/sudden changes in your mood, thoughts, or behavior including signs of depression, suicidal thoughts/attempts, thoughts about harming yourself.

Levetiracetam can commonly cause a rash that is usually not serious. However, you may not be able to tell it apart from a rare rash that could be a sign of a severe reaction. Tell your doctor right away if you develop any rash.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, such as: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US – Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www. fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Precautions

Before taking levetiracetam, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease (such as dialysis treatment), mental/mood disorders (such as depression).

This drug may make you dizzy or drowsy, especially during the first month of treatment. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, ride a bicycle, or do anything that needs alertness until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Children may be more sensitive to the side effects of the drug, especially mental/mood changes (such as irritability, aggression, agitation, anger, anxiety, depression, thoughts of suicide). Children younger than 4 years may be at greater risk for increased blood pressure while using this drug (see also Notes section).

Older adults may be more sensitive to the side effects of this drug, especially drowsiness, dizziness or loss of coordination. These side effects can increase the risk of falling.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

This medication passes into breast milk. Consult your doctor before breast-feeding.

Interactions

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.

A product that may interact with this drug is: orlistat.

Does Keppra interact with other drugs you are taking?

Enter your medication into the WebMD interaction checker

Overdose

If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include slow/shallow breathing, loss of consciousness.

Do not share this medication with others.

Lab and/or medical tests (such as kidney function, complete blood count) may be done while you are taking this medication. In children younger than 4 years, blood pressure may also be monitored. Consult your doctor for more details.

If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

Images

Keppra 1,000 mg tablet

Color: whiteShape: oblongImprint: ucb 1000

This medicine is a white, oblong, scored, film-coated, tablet imprinted with “ucb 1000”.

Keppra 750 mg tablet

Color: orangeShape: oblongImprint: ucb 750

This medicine is a white, oblong, scored, film-coated, tablet imprinted with “ucb 1000”.

Keppra 250 mg tablet

Color: blueShape: oblongImprint: ucb 250

This medicine is a white, oblong, scored, film-coated, tablet imprinted with “ucb 1000”.

Keppra 500 mg tablet

Color: yellowShape: oblongImprint: ucb 500

This medicine is a white, oblong, scored, film-coated, tablet imprinted with “ucb 1000”.

Keppra 100 mg/mL oral solution

Color: colorlessShape: Imprint:

This medicine is a white, oblong, scored, film-coated, tablet imprinted with “ucb 1000”.

Selected from data included with permission and copyrighted by First Databank, Inc. This copyrighted material has been downloaded from a licensed data provider and is not for distribution, except as may be authorized by the applicable terms of use.

CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.

Keppra: 7 things you should know

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Medically reviewed by Carmen Fookes, BPharm. Last updated on May 26, 2022.

1. How it works

• Keppra is a brand (trade) name for levetiracetam which may be used for the treatment of certain types of seizures.
• Experts aren’t sure exactly how levetiracetam works but suggest it dampens down excessive nerve firing and reduces seizure propagation, possibly through an impact on pathways involving calcium, glycine, and GABA.
• Keppra belongs to the class of medicines known as anticonvulsants (also called antiepileptics).

2. Upsides

• Used in combination with other anticonvulsants for the treatment of partial-onset seizures in adults and children over the age of 1 month, for generalized tonic-clonic seizures in adults and children over the age of 6, and the treatment of myoclonic seizures in adults and adolescents over the age of 12.
• Does not require monitoring of blood concentrations.
• Available as oral tablets, extended-release tablets (Keppra-XR), and as an oral solution. The oral solution should be prescribed for children with a body weight less than or equal to 20kg. The oral solution or tablets may be given to children weighing more than 20kg. Only calibrated measures (not household spoons) should be used to measure the oral solution.
• Usually taken once or twice daily.
• Available as 250mg, 500mg, 750mg, and 1000mg tablets and a 100mg/mL oral solution.
• The usual initial dosage in adults 16 years and older is 500mg twice a day. The dosage may be increased every two weeks as needed to a maximum of 1500mg twice a day.
• Keppra is available as a generic under the name levetiracetam.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Drowsiness which may affect your ability to drive or operate machinery. Avoid alcohol.
• Aggression, nasal congestion, headache, decreased appetite, infection, dizziness, pain, sore throat, depression, nervousness, and fatigue are reasonably common side effects. Hematologic abnormalities, coordination difficulties, and serious dermatological reactions (for example, Stevens-Johnson syndrome [SJS] and toxic epidermal necrolysis [TEN]) have also been reported.
• Young children are more likely than adults to experience behavioral abnormalities (eg, overactivity or agitation) or psychotic symptoms as well as other side effects such as a decreased appetite, increased blood pressure, or nasal congestion while taking Keppra.
• As with other antiepileptics, Keppra may increase the risk of suicidal thoughts or behavior. Monitor for worsening depression or mood changes. Keppra may also cause behavioral problems such as aggression, anxiety, irritability, and nervousness; advise people taking Keppra to monitor their mood.
• The dosage of Keppra needs to be reduced in people with kidney disease.
• May not be suitable for some people including those with kidney disease, with a history of mental health problems, who are pregnant or breastfeeding.
• May interact with some medications, such as propoxyphene, buprenorphine, and sedating antihistamines; however, generally, less likely to interact with other medications than some other anticonvulsants.
• In children aged 1 month to 4 years, Keppra has been associated with an increase in blood pressure.
• Alcohol may worsen the side effects of Keppra such as drowsiness and dizziness.
• Withdrawal of Keppra may cause an increase in seizure frequency. Keppra should be tapered off slowly on discontinuation.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

• Keppra is an anticonvulsant that is used in conjunction with other medications for the treatment of certain types of seizures. It may cause drowsiness but it is less likely than some other anticonvulsants to interact with other medications.

5. Tips

• Keppra may be given with or without food.
• Take exactly as directed. Do not increase or decrease the dosage without your doctor’s advice.
• If you are giving Keppra solution to a child or taking it yourself, use the dosing syringe provided or use a properly calibrated liquid measure (these can be bought from a drug store). Do not use a kitchen teaspoon.
• Extended-release tablets should be swallowed whole. Do not crush, chew or break.
• When it comes time to discontinue Keppra, your doctor will advise you on a slowly tapering dosing schedule. Do not just stop it suddenly unless your doctor has advised you that a rapid withdrawal is justified.
• Talk to your doctor if you feel like your mood has changed for the worse or if you have any thoughts about suicide or self-harm. Keppra may also cause aggression, anxiety, depression, and irritability.
• Keppra may cause drowsiness or coordination difficulties and affect your ability to drive or operate machinery. Avoid alcohol.
• Talk to your doctor immediately if you develop a rash or any other worrying side effects while taking Keppra.

6. Response and effectiveness

• Keppra is rapidly and almost completely absorbed after oral administration. It reduces seizure frequency by about half in 20 to 40% of people who take it.
• Keppra tablets and the oral solution are absorbed to the same extent.

7. Interactions

Medicines that interact with Keppra may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Keppra. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with Keppra include:

• antidepressants, such as SSRIs (eg, escitalopram, fluoxetine) and monoamine oxidase inhibitors, such as isocarboxazid, selegiline, or tranylcypromine
• antiepileptics, such as carbamazepine and phenytoin
• benzodiazepines, such as diazepam, oxazepam, and temazepam
• brivaracetam
• buprenorphine
• clozapine
• mefloquine
• methotrexate
• methotrimeprazine
• minocycline
• metoclopramide
• opioids, such as methadone, oxycodone, morphine, or codeine
• sedatives, or any medication that causes sedation, such as sedating antihistamines, sleeping pills, or muscle relaxants
• tramadol.

Alcohol may enhance the sedative effects of Keppra.

Note that this list is not all-inclusive and includes only common medications that may interact with Keppra. You should refer to the prescribing information for Keppra for a complete list of interactions.

More about Keppra (levetiracetam)

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Patient resources

• Drug Information
• Keppra (Levetiracetam Intravenous) (Advanced Reading)
• Keppra (Levetiracetam Oral) (Advanced Reading)
• Keppra (Levetiracetam Injection)
• Keppra (Levetiracetam Oral Solution)
• Keppra (Levetiracetam Tablets)

Other brands

Spritam, Roweepra, Elepsia XR, Roweepra XR

Professional resources

• Prescribing Information

Other formulations

• Keppra XR

Related treatment guides

• Epilepsy
• Seizures

References

• Keppra (levetiracetam) [Package Insert]. Revised 10/2020. UCB, Inc.https://www.drugs.com/pro/keppra.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Keppra only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2023 Drugs.com. Revision date: May 25, 2022.

Medical Disclaimer

The use of levetiracetam in the treatment of children with cancer

Anticonvulsant

Trademarks:

Keppra®, Spiratam®

Often used for:

Seizures

Levetiracetam is a drug that helps relieve seizures.

During therapy, tests may be performed to monitor the level of levetiracetam in the blood. Depending on the content in the blood, the dosage of the drug may vary.

This drug is available in regular and extended release forms. Follow dosage instructions carefully.

Administered intravenously (through a drip) in liquid form

Oral tablets

Oral liquid form

• Drowsiness
• Increased fatigue or general weakness
  
• Nausea and vomiting
• Loss of appetite
• Dizziness
• Loss of balance or coordination
• Diarrhea
• Constipation
• Abdominal pain
• Headache
• Stuffy nose
• Sleep disorders
• Irritability, mood swings or personality changes

The listed side effects are not observed in all patients who are prescribed levetiracetam. The most common side effects are highlighted in bold, but others are not excluded. Report all possible side effects to your doctor or pharmacist.

Be sure to discuss these and other recommendations with your doctor or pharmacist.

• This drug may cause dizziness and drowsiness and increase the risk of falls.
• You can stop taking levetiracetam only in consultation with your doctor.
• Patients of reproductive age who have been prescribed levetiracetam should consult their doctor before planning pregnancy.
• Pregnant or breastfeeding patients should notify their physician.

Levetiracetam home use:

• The drug should be taken at the same time every day.
• The tablets should be swallowed whole. Do not crush or chew before taking.
• Absorbable tablets (Spritam®) should be held on the tongue until completely dissolved (about 10 seconds) and then taken with a sip of liquid. You can also dissolve the tablet in 1 teaspoon of liquid and swallow immediately. Pour some more liquid into the glass and drink to get the full dose of the drug. It is not allowed to swallow the drug whole, as well as crush or chew it.
• When taking levetiracetam in liquid form, measure the dosage using the measuring device included in the kit.
• Store at room temperature.
• Take your dose as soon as possible if you miss it. Do not do this only if there are no more than 4 hours left until the next appointment. In no case do not double the dose at the next dose!
• Do not use an expired drug.
• Follow instructions for safe storage and disposal of this product.

Learn more about levetiracetam

KEPPRA R-R/DOSAGE 100MG/ML 300ML COMPLETE WITH MEASURING SYRINGE

Composition

1 ml of solution contains:

active substance 90 069 : levetiracetam – 100 mg,

excipients: sodium citrate 1.05 mg, citric acid monohydrate 0.06 mg, methyl parahydroxybenzoate 2.70 mg, propyl parahydroxybenzoate 0.30 mg, ammonium glycyrrhizate 1.50 mg, glycerol 85% 235.50 mg, maltitol 300.00 mg, acesulfame potassium 4.50 mg, grape flavor 501040A 0.30 mg, purified water 504.00 mg.

Dosage form

Oral solution.

Description

Solution: is a clear, almost colorless solution with a characteristic odour.

Pharmacodynamics

Pharmacodynamics -pyrrolidine-acetamide), differs in chemical structure from known antiepileptic drugs funds.

Mechanism of action

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. Experiments in vitro and in vivo showed that levetiracetam does not affect the basic characteristics of cells and normal transmission.

In vitro studies showed that levetiracetam affects the intraneuronal concentration of Ca 9 ions0163 2+ , partially inhibiting Ca ²⁺ current through N-type channels and reducing the release of calcium from intraneuronal depots. In addition, levetiracetam partially restores currents through GABA- and glycine-dependent channels, reduced by zinc and -carbolines.

One of the proposed mechanisms is based on proven binding to the SV2A synaptic vesicle glycoprotein found 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 neuronal activity.

Levetiracetam also acts on GABA and glycine receptors, modulating these receptors through various endogenous agents. Does not change normal neurotransmission, but suppresses epileptiform neuronal bursts induced by the GABA agonist bicuculin and excitation of glutamate receptors.

Pharmacodynamic effects

The activity of the drug has been confirmed in relation to both focal and generalized epileptic seizures (epileptiform manifestations / photoparoceismal reaction). Levetiracetam induces protection against seizures in a variety of animal models.

Adjunctive therapy for partial seizures with or without secondary generalization in adults, adolescents and children from 1 month of age with epilepsy -x double-blind, placebo-controlled studies . It was shown that the ratio of patients who demonstrated a 50% or more decrease in the frequency of partial seizures per week from baseline when taking levetiracetam at doses of 1000 mg, 2000 mg or 3000 mg in two doses for 12-14 weeks was 27. 7%. , 31.6% and 41.3%, respectively, and 12.6% in patients taking placebo.

Pediatric population

The efficacy of levetiracetam in patients aged 4 to 16 years was established in a double-blind, placebo-controlled study lasting 14 weeks, including 198 patients. The dose of levetiracetam was 60 mg/kg/day in two divided doses.

44.6% of patients treated with levetiracetam and 19.6% of patients treated with placebo demonstrated a 50% or more reduction in the frequency of partial seizures per week from baseline.

During treatment, 11.4% of patients were seizure free for at least 6 months and 7.2% for at least one year.

The efficacy of levetiracetam in patients aged 1 month to 4 years was established in a double-blind, placebo-controlled study of 116 patients with a treatment duration of 5 days. The dose of levetiracetam oral solution for infants from one to 6 months was 20 mg/kg/day in two doses, followed by titration to 40 mg/kg/day, for infants and children from 6 months to 4 years – 25 mg/day. kg/day in two doses, followed by titration to 50 mg/kg/day.

For initial efficacy evaluation, responder rates (percentage of patients with a 50% or greater reduction in the frequency of partial seizures per day from baseline) were determined using an anonymous reader during a 48-hour video electroencephalography. The performance indicator is based on an analysis of 109 patients who underwent electroencephalography for at least 24 hours. Responders were 43.6% of patients taking levetiracetam and 19.6% of patients taking placebo. During long-term treatment, 8.6% of patients were seizure free for at least 6 months and 7.8% for at least 1 year.

Monotherapy for partial seizures with or without secondary generalization in patients over 16 years of age with newly diagnosed epilepsy blind study on 576 patients from the age of 16 with newly or recently diagnosed epilepsy with unprovoked partial seizures or generalized tonic-clonic seizures. Patients were randomly selected to receive controlled release carbamazepine 400-200 mg/day or levetiracetam 1000-3000 mg/day. The duration of treatment was up to 121 weeks depending on the response.

The absence of seizures within 6 months was observed in 73% of patients taking levetiracetam and 72.8% of patients taking controlled release carbamazepine. The agreed-upon absolute difference between treatments was 0.2% (95% confidence interval – 7.8 8.2). More than half of the patients were seizure-free for 12 months (56.6% of patients on levetiracetam and 58.5% on controlled release carbamazepine, respectively).

In a clinical practice study, concomitant antiepileptic drugs could be discontinued for a limited number of patients who responded to adjunctive levetiracetam therapy (36 adult patients out of 69).

Adjunctive therapy for myoclonic seizures in adults and adolescents from 12 years of age with juvenile myoclonic epilepsy with idiopathic generalized epilepsy with various syndromes myoclonic seizures. Most of the patients had juvenile myoclomic epilepsy. The dose of levetiracetam was 3000 mg/day in two divided doses. 58.3% of patients taking levetiracetam and 23.3% of patients taking placebo had at least a 50% reduction in myoclonic seizures per week. During continuous long-term treatment, 28.6% of patients were free of myoclonic seizures for at least 6 months and 21% of patients for at least one year.

Adjunctive therapy of primary generalized convulsive (tonic- clonic) seizures in adults and adolescents from 12 years of age with idiopathic generalized epilepsy

Efficacy of Leve tiracitam was established during a 24-week, double-blind, placebo-controlled study , which included adults, adolescents and a limited number of children with idiopathic generalized epilepsy with primary generalized tonic-clonic seizures, with various syndromes (juvenile myoclonic epilepsy, juvenile absence epilepsy, childhood absence epilepsy or epilepsy with generalized tonic-clonic convulsions on awakening) .

In this study, the daily dose of levetiracetam was 3000 mg/day for adults and adolescents or 60 mg/kg/day for children in two divided doses. 72.2% of patients taking levetiracetam and 45.2% of patients taking placebo showed a reduction in the frequency of seizures during the week by 50% or more in patients with primary generalized tonic-clonic seizures.

During continuous long-term treatment, 47.4% of patients were free of tonic-clonic seizures for at least 6 months and 31.5% of patients were free of tonic-clonic seizures for at least one year.

Pharmacokinetics

Levetiracetam has a high solubility and permeability. The pharmacokinetic profile is linear with low variability and is comparable in healthy volunteers and patients with epilepsy. After repeated administration, no change in clearance was observed.

No dependence of pharmacokinetics on sex, race and time of day was observed. Absorption occurs completely and is linear, due to which plasma concentration can be predicted based on the dose of levetiracetam taken, expressed in mg / kg of body weight.

In adults and children, there was a significant correlation between salivary and plasma concentrations (the saliva/plasma concentration ratio ranged from 1 to 1. 7 for tablets and similarly 4 hours after oral administration for solution).

Absorption

After oral administration, levetiracetam is well absorbed from the gastrointestinal tract. The degree of absorption does not depend on the dose and time of ingestion. Bioavailability is approximately 100%. Maximum plasma concentration (C _max ) is achieved 1.3 hours after oral administration of levetiracetam at a dose of 1000 mg and with a single dose is 31 μg / ml, after repeated administration (2 times a day) – 43 μg / ml.

Distribution

Plasma protein binding of levetiracetam and its main metabolite is less than 10%. The volume of distribution (V _d ) is approximately 0.5-0.7 l/kg.

Metabolism

Levetiracetam is not actively metabolized in the human body. The main route of metabolism (24% of the dose) occurs by enzymatic hydrolysis of the acetamide group. The formation of the primary pharmacologically inactive metabolite (ucb L057) occurs without the participation of cytochrome P ₄₅₀ liver. Hydrolysis of the acetamide group was minimal for a large number of tissues, including blood cells.

Two minor metabolites have also been identified. The first is obtained by hydroxylation of the pyrrolidone cycle (1.6% of the dose) and the second – by opening the pyrrolidone cycle (0.9% of the dose). Other components found are 0.6% of the dose.

Levetiracetam does not affect the enzymatic activity of hepatocytes. Under in vitro conditions, levetiracetam and its main metabolite did not inhibit the main isoenzymes of cytochrome P ₄₅₀ (CYP3A4, 2A6, 2C9, 2C19, 2D6, 2E1 and 1A2), as well as the activity of glucuronyl transferase (UGT1A1 and UGT1A6) and epoxide hydroxylase. Levetiracetam also did not affect the glucuronidation of valproic acid in vitro .

In cultured human hepatocytes, levetiracetam has no or very little effect on the enzymatic activity of CYP1A2, SULT1E1 and UGT1A1 hepatocytes. Levetiracetam causes a slight induction of CYP2B6 and CYP3A4.

Breeding

Most of the drug (95%) is excreted by the kidneys (about 93% is excreted within 48 hours). The share of the total excretion of levetiracetam and its main metabolite accounted for 66% and 24% of the dose, respectively. The renal clearance of levetiracetam and ucb L057 was 0.6 and 4.2 ml/min/kg, respectively. This suggests that levetiracetam is eliminated by glomerular filtration followed by tubular reabsorption, and that the primary metabolite of the drug is eliminated by active tubular secretion in addition to glomerular filtration. Levetiracetam elimination correlates with creatinine clearance.

Excretion in faeces is 0.3% of the dose.

The mean total clearance is 0.96 ml/min/kg.

The half-life (T _1/2 ) from the blood plasma of an adult is 7 1 h and does not depend on the route of administration and the dosing regimen or repeated administration.

In elderly patients T _1/2 increases by 40% and is 10-11 hours, which is associated with impaired renal function in this category of people.

In patients with impaired renal function clearance of levetiracetam and its primary metabolite correlates with creatinine clearance. Therefore, in patients with renal insufficiency, dose adjustment is recommended depending on creatinine clearance and the degree of renal insufficiency. In end-stage renal disease in adult patients T _1/2 is 25 hours between dialysis sessions and 3.1 hours during dialysis. During a 4-hour dialysis session, up to 51% of levetiracetam is removed.

There are no significant changes in levetiracetam clearance in patients with mild to moderate hepatic impairment . In most patients with severe hepatic impairment with concomitant renal insufficiency, the clearance of levetiracetam is reduced by more than 50%.

Children aged 4 to 12 years

T _1/2 in children aged 4-12 years after a single oral administration of the drug at a dose of 20 mg/kg of body weight is 6 hours. The total clearance of levetiracetam in children aged 4-12 years is approximately 30% higher than in adults and is directly related to body weight.

After repeated oral administration at a dose of 20-60 mg/kg of body weight to children 4-12 years of age, the maximum plasma concentration is reached after 0.5-1.0 hours and increases linearly and in proportion to the dose. The average value of the total clearance is 1.1 ml / min / kg.

Children from 1 month to 4 years ml is 5.3 hours. The maximum plasma concentration is reached approximately 1 hour after taking the drug. The average value of the total clearance is 1.5 ml / min / kg.

Population pharmacokinetic analysis was performed on patients aged 1 month to 16 years. Clearance and observed volume of distribution were significantly related to body weight (clearance increased in direct proportion to body weight). Age also affected both parameters. This effect was more pronounced in younger patients and decreased with increasing age, becoming negligible by 4 years of age.

Indications for use

As monotherapy in treatment:

• partial seizures with or without secondary generalization in adults and adolescents from 16 years of age with newly diagnosed epilepsy.

As adjunctive therapy in the treatment of:

• partial seizures with or without secondary generalization in adults and children from 1 month of age with epilepsy,
• myoclonic seizures in adults and adolescents from 12 years of age with juvenile myoclonic epilepsy, 9003 7
• primary – generalized convulsive tonic-clonic seizures in adults and adolescents from 12 years of age with idiopathic generalized epilepsy.

Contraindications

Symptoms: drowsiness, agitation, aggressiveness, depression of consciousness, respiratory depression, coma.

Treatment: in the acute period – artificial induction of vomiting and gastric lavage, followed by administration of activated charcoal. There is no specific antidote for levetiracetam. If necessary, symptomatic treatment is carried out in a hospital using hemodialysis (dialysis efficiency for levetiracetam is 60%, for its primary metabolite – 74%).

Use in pregnancy and lactation

Pregnancy trimester of pregnancy.

Overall, these data do not indicate a significant increase in the risk of serious congenital malformations, although a teratogenic risk cannot be completely ruled out. Therapy with multiple antiepileptic drugs is associated with a higher risk of congenital malformations than monotherapy, which makes monotherapy more appropriate in pregnant women.

Adequate and well-controlled clinical studies on the safety of levetiracetam in pregnant women have not been conducted, so the drug should not be prescribed during pregnancy and in women of childbearing function, except in cases of clinical 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, a decrease in the concentration of levetiracetam in plasma was noted. This decrease is more pronounced in the third trimester (up to 60% of the base concentration during the third trimester). Treatment with levetiracetam in pregnant women should be carried out under special supervision. Interruptions in antiepileptic therapy can lead to a worsening of the course of the disease, which can harm the health of both the mother and the fetus.

To monitor the effects of levetiracetam use in pregnant women, physicians are advised to register patient data with the European and International Registry for Antiepileptic Drugs (BURAP).

Breastfeeding period

Levetiracetam is excreted in breast milk, so breastfeeding during treatment with the drug is not recommended. However, if treatment with levetiracetam is necessary during a feeding period, the risk/benefit ratio of treatment should be carefully weighed against the importance of feeding.

Fertility

No effect on fertility found in animal studies. There are no clinical data on the effect on fertility, the potential risk to humans is unknown.

Interaction

Antiepileptic drugs

gabapentin, topiramate and primidone) and these antiepileptic drugs do not affect concentration of levetiracetam.

Clearance of levetiracetam was 22% higher in children taking anticonvulsants – inducers of microsomal liver enzymes, compared with children not taking them,

Probenecid at a dose of 500 mg 4 times a day. The effect of levetiracetam when taken simultaneously with probenecid has not been studied, nor is it known when taken with drugs such as non-steroidal anti-inflammatory drugs, sulfonamides and methotrexate.

Contraceptives and other pharmacokinetic interactions

Levetiracetam at a daily dose of 1000 mg does not change the pharmacokinetics of oral contraceptives (ethinyl estradiol and levonorgestrel).

Levetiracetam at a daily dose of 2000 mg does not change the pharmacokinetics of digoxin and warfarin.

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

Antacids

There are no data on the effect of antacids on the absorption of levetiracetam.

Food intake and alcohol

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

There are no data on the interaction of levetiracetam with alcohol.

Overdose

Symptoms: drowsiness, agitation, aggressiveness, depression of consciousness, respiratory depression, coma.

Treatment: in the acute period – artificial induction of vomiting and gastric lavage, followed by the appointment of activated charcoal. There is no specific antidote for levetiracetam. If necessary, symptomatic treatment is carried out in a hospital using hemodialysis (dialysis efficiency for levetiracetam is 60%, for its primary metabolite – 74%).

Special instructions

Cancel therapy

If you want to stop taking the drug, then the treatment of treatment is recommended gradually (in adults and adolescents weighing more than 50 kg), reducing a single dose by 500 mg every 2-4 weeks . In children, the dose reduction should not exceed 10 mg/kg body weight 2 times a day every 2 weeks; in children less than 6 months, the dose reduction should not exceed 7 mg/kg body weight 2 times a day every 2 weeks.

Concomitant antiepileptic drugs (during the transition of patients to levetiracetam) should preferably be discontinued gradually. Available data on the use of the drug in children do not indicate any negative effect on development and puberty. However, the long-term effects of treatment on children’s ability to learn, their intellectual development, growth, endocrine gland function, sexual development and fertility remain unknown.

Liver and kidney disease

In patients with kidney disease and decompensated liver disease, it is recommended to test the kidney function before starting treatment. In case of impaired renal function, dose adjustment may be required.

Suicidal intent

In connection with the reports of cases of suicide, suicidal intent and suicide attempts during treatment with levetiracetam, patients should be warned to immediately inform their doctor of any symptoms of depression or suicidal intent.

Oral solution contains maltitol, therefore patients with impaired fructose tolerance should not take Keppra in the appropriate dosage form.

Oral solution also contains methyl parahydroxybenzoate and propyl parahydroxybenzoate, which may cause allergic reactions (possibly delayed).

Influence 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 different individual sensitivity to the drug from the central nervous system during the period of treatment (some patients may experience drowsiness), it is necessary to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and psychomotor speed reactions.