Levetiracetam

Levetiracetam:

• is an S-enatiomer pyrrolidine derivative, related to piracetam
• is a well-tolerated and effective treatment adjunctive treatment for adults with partial seizures refractory to current anti-epileptic drugs (1). Evidence suggests that levetiracetam seems to at least halve seizure frequency in about 40% of such patients, and around 1 in 16 patients become seizure-free
• has an unknown mode of action in epilepsy but does not seem to involve the recognised sites of action of current anti-epileptic drugs
• has a plasma half-life of 6-8 hours in healthy young adults - the half-life rises to 10-11 hours in patients with mild or moderate renal impairment (creatinine clearance 30-70ml/minute), and to around 24 hours if creatinine clearance is less than 30ml/minute or if there is severe hepatic impairment accompanied by any degree of renal impairment
• does not alter liver enzyme activity
• adverse effects of levetiracetam include:
  • based on evidence from short-term randomised trials
    • commonest adverse effects - somnolence, "asthenia", dizziness
    • treatment with levetiracetam was associated with behavioural symptoms (emotional lability, agitation, hostility, depression) in 13% of patients (vs. 6% on placebo), co-ordination problems (abnormal gait, ataxia) in 3.4% (vs. 1.6%), and, rarely, psychotic symptoms
    • infection (mainly of the upper respiratory tract) was more common than with placebo (13% vs. 7.5%; p=0.005)
  • limited long-term data suggest a similar spectrum of adverse effects as observed in short-term studies
• there should be a 50% reduction in does in patients with a creatinine clearance of 30-50ml/minute (so creatinine clearance should be checked in older patients before initiating treatment), and in those with severe hepatic impairment plus creatinine clearance of less than 70ml/minute. Due to limited experience, this drug should be avoided in women who are or plan to become pregnant, unles its use is "clearly necessary" (2). Levetiracetam should be avoided in women who are breast-feeding. Patients taking this drug should be warned about drowsiness and other adverse central effects

The summary of product characteristics should be consulted before prescribing this drug.

1. Drugs and Therapeutics Bulletin (2002), 40 (4), 30-32.
2. Keppra. Summary of product characteristics. UCB Pharma Ltd, October 2000.