II. 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)

III. 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)

IV. Dosing: Status Epilepticus

  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

V. Dosing: Seizure Prophylaxis in Adults

  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

VI. Dosing: Seizure Prophylaxis in Children

  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)

VII. 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 or hostility
    2. Emotional lability
    3. Anxiety
    4. Depressed mood
  3. Other symptoms
    1. Irritability
    2. Rash

VIII. Safety

  1. Safe in children
  2. Pregnancy Category C
  3. Unknown safety in Lactation

IX. Metabolism

  1. Rapid oral absorption
  2. Renal Excretion
    1. Decrease dose in renal Impairment

X. Drug Interactions

  1. May result in toxicity if used with carbamezepine
  2. Low risk for other Drug Interactions

XII. 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]

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Cost: Medications

levetiracetam (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
LEVETIRACETAM 1,000 MG TABLET Generic $0.19 each
LEVETIRACETAM 100 MG/ML SOLN Generic $0.03 per ml
LEVETIRACETAM 250 MG TABLET Generic $0.07 each
LEVETIRACETAM 500 MG TABLET Generic $0.09 each
LEVETIRACETAM 750 MG TABLET Generic $0.14 each
LEVETIRACETAM ER 500 MG TABLET Generic $0.20 each
LEVETIRACETAM ER 750 MG TABLET Generic $0.30 each
keppra (on 1/1/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
KEPPRA 1,000 MG TABLET Generic $0.19 each
KEPPRA 100 MG/ML ORAL SOLN Generic $0.03 per ml
KEPPRA 250 MG TABLET Generic $0.07 each
KEPPRA 500 MG TABLET Generic $0.09 each
KEPPRA 750 MG TABLET Generic $0.14 each
KEPPRA XR 500 MG TABLET Generic $0.20 each
KEPPRA XR 750 MG TABLET Generic $0.30 each