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Levetiracetam

The mode of action of levetiracetam is not yet known, although a specific binding site for the drug has been shown to exist. Levetiracetam is rapidly absorbed from the gastrointestinal tract, is not protein bound and exhibits linear pharmacokinetics. It is minimally metabolised and excreted unchanged via the kidneys.

Indications

Levetiracetam is licensed for monotherapy and adjunctive treatment of partial seizures with or without secondary generalisation, and for adjunctive therapy of myoclonic seizures.1,2

Cautions
  • Hepatic impairment (halve the dose in severe liver failure)
  • Renal impairment
  • Pregnancy (toxicity shown in animal studies)
  • Avoid sudden withdrawal
Interactions
  • Levetiracetam has no propensity to interact with other antiepileptic drugs and no definite interactions with other drugs have so far been identified.
Common problems
  • Levetiracetam is well tolerated overall and no idiosyncratic side effects have yet been described
  • Drowsiness, dizziness, asthenia, ataxia and irritability (all usually transient)
Other side-effects

Less common side effects include:

  • Anorexia, diarrhoea, dyspepsia, nausea
  • Amnesia, depression, emotional lability, aggression, insomnia, nervousness, tremor, vertigo, headache, diplopia
  • Rash
  • Anxiety, psychosis, leucopenia, pancytopenia, thrombocytopenia have also been reported
Initiation
  • Monotherapy of partial seizures with or without secondary generalisation:
    • Adult and adolescent over 16 years: initially 250 mg twice daily increased according to response in steps of 250 mg twice daily every 2 weeks; maximum dose 1.5 g twice daily.
  • Adjunctive therapy of partial seizures and myoclonic seizures:
    • Adult and adolescent over 12 years, body-weight over 50 kg: initially 500 mg twice daily, adjusted in steps of 500 mg twice daily every 2 to 4 weeks; maximum dose 1.5 g twice daily.
    • Child and adolescent 4-18 years (12-18 years for myoclonic seizures), body-weight under 50 kg: initially 10 mg/kg twice daily, adjusted in steps not exceeding 10 mg/kg twice daily every 2 weeks; maximum dose 30 mg/kg twice daily.
Monitoring
  • Monitoring of plasma drug levels is not routinely recommended. There is little published information on levetiracetam blood levels in patients with epilepsy.
  • Clinical trials data for levetiracetam suggests a target range of 35-110 mcmol/L.
  • Levetiracetam is measurable in saliva but the relationship between plasma and saliva concentrations has not yet been established.

Document references
  1. Specifiic Product Characteristics - Keppra® (levetiracetam) 250,500,750 and 1000 mg film-coated Tablets, 100 mg/ml oral solution and 100 mg/ml concentrate for solution for infusion, UCB Pharma Limited, Updated Jan 2007, electronic Medicines Compendium.
  2. The diagnosis and management of the epilepsies in adults and children in primary and secondary care; NICE Clinical Guideline October 2004.
Internet and further reading
  • NSE; The National Society for Epilepsy - Professionals page.
  • NSE; The National Society for Epilepsy - Home page.
  • Epilepsy, Clinical Knowledge Summaries (2007)
  • Perkin GD; Oxford Textbook of Medicine 4th edition; Section 24.17 Epilepsy in later childhood and adults.
AcknowledgementsEMIS is grateful to Dr Colin Tidy for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2008.
DocID: 347
Document Version: 2
DocRef: bgp25086
Last Updated: 22 Feb 2008
Review Date: 21 Feb 2009






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