levetiracetam (Keppra)

see also:

• anticonvulsants
• seizures

• levetiracetam is a newer anticonvulsant with similar efficacy as phenytoin for status epilepticus but without the iv line incompatibility issues
• main mechanism involves binding to the synaptic vesicle protein 2A (SV2A), a key component of nerve cell vesicles, which modulates neurotransmitter release, potentially by inhibiting presynaptic calcium channels and reducing glutamate release, likely reducing excessive electrical signaling that causes seizures, without affecting normal brain activity
• may also inhibit N-type calcium channel currents
• useful for:
  • partial onset seizures (monotherapy)
  • myoclonic seizures (as add on)
  • primary generalized tonic-clonic seizures (as add on)

• (off-label use)
• iv 25mg/kg (usually 1g in adults) over 15 min
• alternatively, some use up to 60mg/kg or 4.5g at 2 to 5 mg/kg/minute
• although not well studied, appears to be as effective as phenytoin but without the iv line incompatibility issues but may not be as effective as sodium valproate (Epilim) as a 2nd line for status

• (off-label use)
• prophylaxis of seizures
• load: iv 20mg/kg (rounded to nearest 250mg in adults) over 60 min
• maintenance: iv 1g over 15min every 12hrs for 7 days

• adjust dosing for renal impairment

• Mx of status epilepticus as 2nd line medication: IV or IO 60 mg/kg up to 4500 mg, over 5 minutes
• when switching from oral dosing to iv dosing, daily dose should be the same
• usual initial maintenance dosing:
  • iv 500mg twice daily
  • may need to increase every 2 weeks by further 500mg/dose to max. of 1.5g bd

• immediate release tablets
  • 500mg bd, may need to increase every 2 weeks by further 500mg/dose to max. of 1.5g bd
• extended release tablets
  • initially 1g daily, increase every 2 weeks by further 1g/d as needed to max. 3g daily

• increased BP
• behavioural issues, irritability
• headache
• drowsiness
• aggressive behaviour or psychotic issues (esp. children)
• vomiting
• nasal congestion, nasopharyngitis?
• eosinophilia (esp. children)
• neutropenia or agranulocytosis
• rarely, anaphylaxis or toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS)
• other rare effects

• pregnancy cat C
• lactation
• drug interactions
• renal impairment increases half life

• rapid and almost complete absorption following oral administration (100% bioavilability) with time to peak plasma concentration of around 1hr (4hrs for extended release tablets)
• Vd similar to water (0.5-0.7L/kg)
• less than 25% metabolised, mainly renal excretion with half life of 6-8hrs for adults and 4-7hrs for children