How to manage oversedation from Breviracetam (Brivaracetam), given that Keppra (Levetiracetam) is not an option?

Management of Brivaracetam-Induced Oversedation

Immediately discontinue brivaracetam and provide supportive care with close monitoring of airway, oxygenation, ventilation, and vital signs until sedation resolves. 1

Immediate Management

• Stop brivaracetam immediately as there is no specific antidote for brivaracetam overdose or toxicity 1
• Ensure adequate airway, oxygenation, and ventilation with consideration for intubation if respiratory depression is present 1
• Monitor cardiac rate, rhythm, and vital signs continuously as bradycardia has been reported with brivaracetam overdose 1
• Contact a certified poison control center for updated management guidance 1

The FDA label clearly documents that somnolence and dizziness are the primary manifestations of brivaracetam overdose, with supportive care being the mainstay of treatment 1. Hemodialysis is not expected to enhance brivaracetam clearance since less than 10% is renally excreted 1.

Alternative Antiepileptic Drug Selection

Since levetiracetam is not an option (likely due to similar sedative concerns or prior intolerance), consider these alternatives based on current guidelines:

First-Line Alternatives

• Lamotrigine is recommended as a preferred first-choice option alongside levetiracetam for its efficacy and overall good tolerability 2

  • Note: Requires several weeks to reach therapeutic levels due to slow titration requirements 2
  • Cannot be used for acute seizure control but excellent for maintenance therapy 2

• Lacosamide may assume a larger role as add-on treatment and is available in both oral and IV formulations 2

  • Typical dosing has been studied but loading strategies require further investigation 2
  • Causes mild to moderate dizziness, headache, and somnolence but generally well-tolerated 2

Second-Line Alternatives

• Valproic acid remains effective with overall good tolerability in many centers 2
  • Contraindicated in females of childbearing potential 2
  • No increased risk of perisurgical bleeding despite historical concerns 2
  • Requires regular monitoring for drug interactions 2

Avoid These Agents

• Do not use enzyme-inducing anticonvulsants (phenytoin, phenobarbital, carbamazepine) due to significant side-effect profiles and drug interactions with steroids and chemotherapeutic agents 2

Critical Considerations for Brivaracetam

Cross-reactivity with levetiracetam is a significant concern. Both drugs bind to synaptic vesicle protein 2A (SV2A), and patients who experienced behavioral or psychiatric side effects with levetiracetam may have similar issues with brivaracetam 3, 4. However, the evidence shows:

• 57.1% of patients who switched from levetiracetam to brivaracetam due to psychiatric side effects reported improved tolerability 3
• Conversely, 23.8% of patients with prior levetiracetam intolerance experienced psychiatric side effects with brivaracetam 3
• Overall, brivaracetam causes significantly fewer behavioral adverse events than levetiracetam (22.4% vs 55.1%) 4

Monitoring During Recovery

• Sedation typically resolves rapidly with supportive care alone based on levetiracetam overdose data showing recovery within 24 hours 5
• Brivaracetam exhibits linear, time-independent pharmacokinetics with an elimination half-life of approximately 9 hours in normal conditions 1
• Serial monitoring of mental status and respiratory function is essential until full recovery 1

Common Pitfalls to Avoid

• Do not assume hemodialysis will help - it is not expected to enhance clearance 1
• Do not immediately restart another SV2A ligand (like levetiracetam) without allowing complete washout and resolution of sedation 3
• Do not overlook cardiac monitoring - bradycardia has been reported with brivaracetam toxicity 1
• Do not use benzodiazepines for agitation management if the patient is already oversedated, as this increases risk of respiratory depression 2