Management of Elevated Levetiracetam (Keppra) Level
Reduce the total daily dose immediately and consider hemodialysis if the patient is symptomatic with somnolence, respiratory depression, or altered mental status, as standard hemodialysis removes approximately 50% of levetiracetam in 4 hours. 1
Immediate Assessment
The patient's current regimen totals 2500 mg/day (1000 mg BID + 250 mg BID), and the serum level of 72.7 mcg/mL is approximately 2-6 times the upper therapeutic range (therapeutic range: 10-37 mcg/mL). 2
Evaluate for signs of toxicity:
- Somnolence and drowsiness 1, 2, 3
- Respiratory depression 1, 2
- Depressed level of consciousness or obtundation 1, 2
- Agitation or aggression 1
- Diminished deep tendon reflexes 2
- Asthenia (weakness) 3
Dose Reduction Strategy
Decrease the total daily dose by 25-50% immediately based on the degree of elevation and clinical symptoms. 3
- If asymptomatic: Consider reducing to 1500-2000 mg/day total (e.g., 750-1000 mg BID)
- If symptomatic: Reduce more aggressively to 1000-1500 mg/day total
- The most common adverse events (somnolence and asthenia) increase with higher doses, with 4000 mg/day representing the upper tolerance limit in many patients 3
Hemodialysis Consideration
Hemodialysis should be strongly considered if:
- The patient exhibits significant CNS depression, respiratory depression, or coma 1
- Renal impairment is present (as levetiracetam is primarily renally eliminated) 1
- Standard hemodialysis achieves approximately 50% clearance in 4 hours and is specifically indicated for levetiracetam overdose 1
Supportive Care
Provide general supportive measures: 1
- Monitor vital signs closely
- Maintain airway patency (intubation may be required if respiratory depression develops) 2
- Observe clinical status continuously until levels normalize
- Contact a Certified Poison Control Center for additional guidance 1
Recovery Timeline
Expect rapid recovery with supportive care alone if hemodialysis is not performed. The elimination half-life remains approximately 5-7 hours even at supratherapeutic levels (first-order kinetics maintained), so clinical improvement should occur within 24-48 hours with dose reduction. 2
Follow-up Monitoring
- Recheck levetiracetam level in 24-48 hours after dose adjustment
- Monitor for seizure breakthrough during dose reduction
- Assess renal function, as impaired clearance may have contributed to the elevated level 1
- Complete blood count monitoring is recommended when adjusting levetiracetam therapy 4
Common Pitfall
Do not continue the current dose while "monitoring" the level. Levetiracetam toxicity, while generally well-tolerated compared to other antiepileptics, can cause significant respiratory depression requiring intubation. 2 The lack of a specific antidote makes dose reduction and/or hemodialysis the only definitive management strategies. 1