Generic Name: levetiracetam

Brand and Other Names: Keppra, Keppra XR, Spritam, Elepsia

Drug Class: SV2A Ligands

What is levetiracetam, and what is it used for?

Levetiracetam is an antiepileptic drug used to treat certain types of seizures in adult and pediatric epileptic patients. Levetiracetam is a novel anticonvulsant drug chemically unrelated to any of the other existing anticonvulsant drugs. Levetiracetam has a better safety profile than other anticonvulsants, and interactions with fewer drugs, making it a preferred therapy.

The exact mechanism of levetiracetam’s anticonvulsant effects is not clear. Seizures are caused by abnormal bursts of electrical activity in the brain. Levetiracetam is thought to prevent the spread of seizure activity by preventing the synchronization of burst firing of nerve cells (neurons), without affecting normal neuronal excitability and neurotransmission.

Levetiracetam binds to a unique protein on the membrane of synaptic vesicles known as synaptic vesicle protein 2A (SV2A). Synapse is the junction between two nerve cells in which synaptic vesicles release chemicals (neurotransmitters) to conduct electrical impulses. SV2A regulates the neurotransmitter release, and by binding to SV2A, levetiracetam decreases the release of glutamate, an excitatory neurotransmitter.

Levetiracetam blocks the release of glutamate by also inhibiting N-type calcium channels, which prevents the influx of calcium into the neurons and inhibits action potential. Levetiracetam does not directly have an effect on gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain, but appears to increase GABA activity by blocking the negative modulators of GABA.

Levetiracetam is used to treat the following types of seizures in both adults and children:

  • Myoclonic seizures, a type that causes brief jerks of a muscle or groups of muscles
  • Partial onset seizures, a type that begins in only one part of the brain
  • Primary generalized tonic-clonic seizures, a type that starts on both sides of the brain and causes violent muscle contractions and loss of consciousness
  • Neonatal seizures (orphan designation), that occur in newborn babies

Warnings

  • Do not administer levetiracetam to patients hypersensitive to it or any of its components
  • Antiepileptic drugs, including levetiracetam increases the risk of suicidal thoughts and behavior; caregivers should be advised to monitor the patient for onset or worsening of depression or unusual changes in mood or behavior
  • As with most antiepileptic drugs, levetiracetam should be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus, a state of prolonged seizure lasting longer than five minutes
  • Drowsiness and weakness may occur, especially within the first 4 weeks of treatment; patient must be advised not to drive or operate heavy machinery until any potential adverse drug effects can be gauged
  • Levetiracetam may cause psychiatric reactions such as aggression, anxiety, irritability and personality disorder; monitor and reduce dose or discontinue if necessary; patient and the caregivers must be counseled appropriately
  • Levetiracetam may cause serious skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
  • Drug rash with eosinophilia and systemic syndrome (DRESS), a severe drug reaction has been known to occur with levetiracetam use
  • Can cause blood abnormalities, including decrease in different types of blood cells
  • Can cause severe allergic reaction (anaphylaxis)
  • Physiological changes during pregnancy may gradually decrease drug concentration in blood, particularly during the 3rd trimester; dose adjustments may be required
  • Levetiracetam must be used with caution in patients with impaired kidney function

QUESTION

If you have had a seizure, it means you have epilepsy. See Answer

What are the side effects of levetiracetam?

Common side effects of levetiracetam include:

Less common side effects of levetiracetam include:

Rare side effects of levetiracetam include:

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug.

Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

What are the dosages of levetiracetam?

Tablet, immediate-release (Keppra, Generic)

  • 250 mg
  • 500 mg
  • 750 mg
  • 1 g

3-D tablet, immediate-release (Spritam)

  • 250 mg
  • 500 mg
  • 750 mg
  • 1 g

Tablet, extended-release (Keppra XR)

  • 500 mg
  • 750 mg

Oral solution (Keppra, Generic)

  • 100 mg/mL

Injectable solution

  • 5 mg/mL
  • 10 mg/mL
  • 15 mg/mL
  • 100 mg/mL

Adult:

Myoclonic Seizures

  • Immediate-release (Keppra, Spritam): 500 mg intravenously (IV)/orally every 12 hours; may increase every 2 weeks by 500 mg/dose to recommended dose of 1500 mg every 12 hours
  • Effectiveness of doses less than 3000 mg/day has not been adequately studied

Partial Onset Seizure

  • Indicated for treatment of partial-onset seizures
  • Need for oral loading dose not established
  • Immediate-release (Keppra, Spritam): 500 mg orally every 12 hours; may increase every 2 weeks by 500 mg/dose; not to exceed 3000 mg/day
  • Extended-release (Keppra XR): 1000 mg orally once/day; may increase every 2 weeks by 1000 mg/day; not to exceed 3000 mg/day
  • Intravenous (IV): 500 mg every 12 hours; may increase every 2 weeks by 500 mg/dose; not to exceed 3000 mg/day

Primary Generalized Tonic-Clonic Seizures

  • Need for oral loading dose not established
  • Immediate-release (Keppra, Spritam): 500 mg intravenously (IV)/orally every 12 hours; may increase every 2 weeks by 500 mg/dose to recommended dose of 1500 mg every 12 hours
  • Effectiveness of doses less than 3000 mg/day has not been adequately studied

Renal Impairment

Immediate Release and Intravenous (IV) Formulations

  • Creatinine clearance (CrCl) greater than 80 mL/min/1.73 m²: Dose adjustment not required
  • CrCl 50-80 mL/min/1.73 m²: 500-1000 mg orally every 12 hours
  • CrCl 30-50 mL/min/1.73 m²: 250-750 mg orally every 12 hours
  • CrCl less than 30 mL/min/1.73 m²: 250-500 mg orally every 12 hours
  • Dialysis (conventional): 500-1000 mg orally once/day, THEN 250-500 mg supplemental dose after dialysis

Extended Release Tablets (Keppra XR0

  • CrCl greater than 80 mL/min/1.73 m²: Dose adjustment not required
  • CrCl 50-80 mL/min/1.73 m²: 1000-2000 mg orally every 24 hours
  • CrCl 30-50 mL/min/1.73 m²: 500-1500 mg orally every 24 hours
  • CrCl less than 30 mL/min/1.73 m²: 500-1000 mg orally every 24 hours
  • End-stage renal disease requiring hemodialysis: Immediate release formulation recommended

Extended release tablets (Elepsia XR)

  • CrCl greater than 80 mL/min/1.73 m²: Dose adjustment not required
  • CrCl 50-80 mL/min/1.73 m²: 1000-2000 mg orally every 24 hours
  • CrCl less than 50 mL/min/1.73 m²: Not recommended
  • End-stage renal disease requiring hemodialysis: Immediate release formulation recommended

Dosing Considerations

  • Avoid abrupt withdrawal to reduce the risk of increased seizure frequency and status epilepticus

Pediatric:

Partial Onset Seizures

Immediate-release tablets (Keppra)

  • Indicated for monotherapy or adjunctive treatment of partial-onset seizures in children 1 month and older
  • Children under 1 month: Safety and efficacy not established
  • Children 1-6 months: 7 mg/kg orally every 12 hours; increase by increments of 7 mg/kg every 12 hours every 2 weeks to recommended dose of 21 mg/kg every 12 hours
  • Children 6 months-4 years: 10 mg/kg orally every 12 hours, increase in increments of 10 mg/kg every 12 hours every 2 weeks to recommended dose of 25 mg/kg every 12 hours
  • Children 4-16 years: 10 mg/kg orally every 12 hours; increase every 2 weeks by 10 mg/kg/dose to 30 mg/kg every 12 hours
  • Children over 16 years: 500 mg orally every 12 hours, increase by 500 mg every 12 hours every 2 weeks to recommended dose of 1500 mg every 12 hours

Immediate-release 3-D tablets (Spritam)

  • Indicated for treatment of partial-onset seizures in children 4 years and older
  • Children under 4 years: Safety and efficacy not established
  • Children 4 years and older weighing 20-40 kg: 250 mg orally twice daily initially; increase the daily dose every 2 weeks by increments of 500 mg (250 mg twice daily) to a maximum recommended daily dose of 1500 mg (750 mg twice daily)
  • Children 4 years and older weighing greater than 40 kg: 500 mg orally twice daily initially; increase the daily dose every 2 weeks by increments of 1000 mg (500 mg twice daily) to a maximum recommended daily dose of 3000 mg (1500 mg twice daily)

Extended-release tablets (Keppra XR)

  • Indicated as adjunctive therapy for treatment of partial-onset seizures in children 12 years and older
  • Children under 12 years: Safety and efficacy not established
  • Children 12 years and older: 1000 mg orally once/day initially; may adjust dose by 1000 mg increments every 2 weeks to a maximum of 3000 mg/day

Primary Generalized Tonic-Clonic Seizures

  • Children under 6 years: Safety and efficacy not established

Keppra

  • Children 6-16 years: 10 mg/kg orally every 12 hours; increase every 2 weeks by 10 mg/kg/dose to recommended dose of 30 mg/kg every 12 hours; efficacy of doses less than 60 mg/kg/day not established
  • Children over 16 years: 500 mg orally every 12 hours, increase by 500 mg every 12 hours every 2 weeks to recommended dose of 1500 mg every 12 hours

Spritam

  • Children 6 years and older weighing 20-40 kg: 250 mg orally twice daily initially; increase the daily dose every 2 weeks by increments of 500 mg (250 mg twice daily) to a maximum recommended daily dose of 1500 mg/day (750 mg twice daily)
  • Children 6 years and older weighing greater than 40 kg: 500 mg orally twice daily initially; increase the daily dose every 2 weeks by increments of 1000 mg (500 mg twice daily) to a maximum recommended daily dose of 3000 mg (1500 twice daily)
  • Effectiveness of doses less than 3000 mg/day has not been adequately studied

Myoclonic seizures

Keppra, Spritam

  • Children under 12 years: Safety and efficacy not established
  • Children 12 years and older: 500 mg orally every 12 hours; increase by 500 mg every 12 hours every 2 weeks to recommended dose of 1500 mg every 12 hours
  • Effectiveness of doses less than 3000 mg/day has not been studied

Dosing Considerations

  • Avoid abrupt withdrawal to reduce the risk of increased seizure frequency and status epilepticus

IMAGES

Vascular (Multi-Infarct) Dementia Browse our medical image collection to see examples of MRI brain scans, PET scans, and other imaging techniques used to diagnose and treat brain disorders See Images

Overdose

  • Overdose of levetiracetam may cause agitation, aggression, drowsiness, depressed level of consciousness, respiratory depression and coma.
  • There is no specific antidote for levetiracetam. Treatment may include removal of unabsorbed medication from the stomach by induced vomiting or gastric lavage. Hemodialysis may be performed to clear the drug, depending on the patient’s condition or in patients with renal impairment.

What drugs interact with levetiracetam?

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

  • Levetiracetam has no known severe interactions with other drugs.
  • Serious interactions of levetiracetam include:
  • Moderate interactions of levetiracetam include:
    • acalabrutinib
    • brexanolone
    • brivaracetam
    • deutetrabenazine
    • esketamine intranasal
    • ganaxolone
    • lasmiditan
    • lurasidone
    • midazolam intranasal
    • orlistat
  • Levetiracetam has mild interactions with at least 17 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

Pregnancy and breastfeeding

  • There are no adequate and well-controlled studies of levetiracetam use in pregnant women; use during pregnancy only if the potential benefit justifies the potential risk to the fetus
  • Effects of levetiracetam use during labor and delivery is not known
  • Levetiracetam is excreted in breast milk; because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother
  • If you get pregnant during therapy or plan to get pregnant, notify your physician.
  • It may be useful to enroll in the North American Antiepileptic Drug pregnancy registry if you become pregnant; the registry collects information about the safety of antiepileptic drugs during pregnancy. To enroll, call 1-888-233-2334 or visit http://www.aedpregnancyregistry.org

What else should I know about levetiracetam?

  • Take levetiracetam exactly as prescribed.
  • Levetiracetam can increase suicidal thoughts and behavior; caregivers and family should be alert and watch for symptoms of depression or unusual changes in the patient’s mood and behavior.
  • Levetiracetam can cause changes in behavior including aggression, hostility, depression, apathy, anxiety and psychotic symptoms in rare cases. Caregivers and patients may require appropriate counseling.
  • Levetiracetam can cause drowsiness and dizziness; do not drive, operate heavy machinery or engage in other hazardous activities until any potential adverse drug effects can be gauged.

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Summary

Levetiracetam is an antiepileptic drug used to treat seizures in adults and children with epilepsy. Common side effects of levetiracetam include headache, increased blood pressure, drowsiness (somnolence), fatigue, weakness (asthenia), dizziness, infection, loss of appetite (anorexia), inflammation of nose and throat (nasopharyngitis), cough, hostility, nervousness, anxiety, and depression. Consult your doctor before taking levetiracetam if pregnant or breastfeeding.

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Medically Reviewed on 3/28/2022
References
https://www.rxlist.com/consumer_levetiracetam_keppra_spritam/drugs-condition.htm

https://reference.medscape.com/drug/keppra-spritam-levetiracetam-343013#6

https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021035s078s080%2C021505s021s024lbl.pdf

https://www.statpearls.com/ArticleLibrary/viewarticle/24231

https://www.sciencedirect.com/topics/medicine-and-dentistry/n-type-calcium-channel