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Levetiracetam

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Levetiracetam, Keppra, Spiritam

  • Indications
  1. Status Epilepticus
  2. Seizure Prophylaxis
    1. Partial Seizures or Focal onset Seizures (FDA Approved for adjunctive therapy)
    2. Juvenile Myoclonic Epilepsy (FDA approved for ages >12 years for adjunctive therapy)
    3. Primary Generalized Tonic Clonic Seizures (FDA approved for ages >6 years for adjunctive therapy)
  3. Myoclonus (adults, off label)
  • Mechanism
  1. Broad spectrum Pyrrolidine anticonvulsant, with activity isolated to the synaptic plasma membrane of CNS Neurons
  2. Decreases burst Neuron firing (and decreased Seizure propagation) without Neuron normal excitability
  3. Binds Glycoprotein 2A at the synaptic Vesicle and may alter Vesicle fusion
  4. May also affect Gamma-Aminobutyric Acid (GABA)
  1. Dose: 60 mg/kg IV (or 2.5 g in adults, up to 4.5 g maximum) over 5 to 15 min for single dose
  1. Target serum concentration: 12 to 46 mcg/ml
  2. Immediate Release (Keppra, Spiritam)
    1. Start: 500 mg orally or IV twice daily
    2. Titrate every 2 weeks, increasing by 1000 mg/day divided twice daily
    3. Typical target dose: 3000 mg/day (or 80 mg/kg/day) divided twice daily
    4. Maximum: 3000 mg/day (higher doses do not increase efficacy)
  3. Extended Release (Keppra XR for Partial Seizures)
    1. Start 1000 mg orally daily
    2. Titrate every 2 weeks, increasing by 1000 mg/day
    3. Typical target dose: 3000 mg/day (or 80 mg/kg/day)
    4. Maximum: 3000 mg/day (higher doses do not increase efficacy)
  4. Intravenous infusion dose is bioequivalent to oral dose
    1. Load: 20-30 mg/kg IV at 5 mg/kg/min
  1. Age 1 to 6 months (Keppra Solution, oral dosing only)
    1. Start 14 mg/kg/day divided orally twice daily
    2. Increase every 2 weeks by 14 mg/kg/day divided twice daily
    3. Target dose: 42 mg/kg/day divided twice daily
  2. Age 6 months to 4 years (Keppra Solution, oral dosing only)
    1. Start 20 mg/kg/day divided orally twice daily
    2. Increase every 2 weeks by 20 mg/kg/day divided twice daily
    3. Target dose: 50 mg/kg/day divided twice daily
  3. Age 4 to 16 years (oral dosing only)
    1. Keppra Solution
      1. Start 20 mg/kg/day divided orally twice daily
      2. Increase every 2 weeks by 20 mg/kg/day divided twice daily
      3. Target dose: 60 mg/kg/day divided twice daily
    2. Keppra tablets: Weight 20 to 40 kg
      1. Start: 250 mg orally twice daily
      2. Titrate every 2 weeks, increasing by 500 mg/day divided twice daily
      3. Typical target dose: 1500 mg/day divided twice daily
      4. Maximum: 1500 mg/day
    3. Keppra tablets: Weight >40 kg
      1. Start: 500 mg orally twice daily
      2. Titrate every 2 weeks, increasing by 1000 mg/day divided twice daily
      3. Typical target dose: 3000 mg/day divided twice daily
      4. Maximum: 3000 mg/day (higher doses do not increase efficacy)
  4. Age >16 years
    1. Use adult dosing (IV or oral)
  • Adverse Effects
  1. Most common
    1. Fatigue or Weakness
    2. Somnolence
    3. Dizziness or Vertigo
  2. Psychiatric symptoms or Behavioral Changes (common, may limit usage)
    1. Agitation, irritability or hostility
    2. Emotional lability
    3. Anxiety
    4. Depressed mood
  3. Other symptoms
    1. Irritability
    2. Rash
  • Safety
  1. Safe in children
  2. Pregnancy Category C
  3. Unknown safety in Lactation
  • Metabolism
  1. Rapid oral absorption
  2. Renal Excretion
    1. Decrease dose in renal Impairment
  • Drug Interactions
  1. May result in toxicity if used with carbamezepine
  2. Low risk for other Drug Interactions
  • References
  1. LoVecchio and Pringle (2018) Crit Dec Emerg Med 32(12): 28
  2. (2022) Presc Lett, Resource #361206, Antiseizure Medications
  3. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 56-7
  4. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  5. Liu (2017) Am Fam Physician 96(2): 87-96 [PubMed]