What is the management for a perampanel (Fycompa) overdose?

Management of Perampanel Overdose

There is no specific antidote for perampanel overdose; management focuses on supportive care with airway protection, adequate oxygenation and ventilation, continuous cardiac monitoring, and contacting a poison control center for guidance. 1

Initial Assessment and Stabilization

• Immediately secure the airway and ensure adequate oxygenation and ventilation, as this is the first priority in perampanel overdose management 1
• Establish continuous cardiac rhythm monitoring and measure vital signs regularly, as cardiovascular effects including hypotension and bradycardia have been reported 1, 2
• Obtain intravenous access and perform bedside glucose testing to rule out hypoglycemia as a contributing factor to altered mental status 3
• Contact a certified poison control center immediately for updated information on management strategies 1

Expected Clinical Presentation

• The most commonly reported symptoms in perampanel overdose include somnolence, stupor, coma, psychiatric or behavioral reactions (including aggressive "zombielike" behavior), altered mental status, dizziness, and gait disturbances 1, 4, 5
• Cardiovascular effects such as hypotension and bradycardia may occur and can persist for over 32 hours after ingestion 2
• Central nervous system effects including drowsiness (19.6%), agitation (14.5%), ataxia (9.4%), and confusion (8.7%) are frequently observed 4
• Approximately 19% of reported cases developed moderate to major effects, with nearly 4% requiring potentially life-saving interventions 4

Supportive Care Management

• Provide respiratory support as needed, including bag-mask ventilation or endotracheal intubation for patients with significant respiratory depression 6, 7, 1
• Treat hypotension with intravenous fluid resuscitation; bradycardia may improve with stimulation and fluid administration 2
• For severe agitation or behavioral disturbances, benzodiazepines are the first-line treatment and should be titrated to achieve adequate sedation 3, 4
• Continuous dexmedetomidine infusion combined with intravenous lorazepam boluses has been successfully used for managing severe aggressive behavior in perampanel toxicity 5

Critical Considerations Due to Perampanel's Pharmacokinetics

• Be prepared for prolonged symptoms due to perampanel's extremely long half-life of approximately 105 hours 1, 2
• Patients require extended observation periods, as clinical effects can persist for several days after ingestion 1, 2, 8
• Quantitative perampanel levels can be obtained but do not typically guide acute management decisions 2
• Symptoms may gradually improve over 3-5 days with supportive care alone 2, 5, 8

Disposition and Monitoring

• Patients with significant CNS depression, cardiovascular instability, or behavioral disturbances should be admitted to an intensive care unit for continuous monitoring 2, 4
• Those with mild symptoms may be managed in a non-critical care unit, but observation should continue until vital signs normalize and mental status returns to baseline 2, 4, 8
• Approximately 43% of healthcare facility cases can be treated and released, while 28% require non-critical care admission and 18% need critical care admission 4
• Continue monitoring for at least 24-48 hours after symptom resolution given the prolonged half-life 1, 2

Common Pitfalls to Avoid

• Do not assume naloxone or flumazenil will be helpful, as perampanel is neither an opioid nor a benzodiazepine; these antidotes have no role in pure perampanel toxicity 6, 3
• Avoid underestimating the duration of toxicity—symptoms can persist for days due to the 105-hour half-life 1, 2
• Do not discharge patients prematurely; ensure complete resolution of neurologic and cardiovascular symptoms before discharge 2, 8
• Be aware that even relatively small overdoses in pediatric patients or those with low body mass index can produce significant CNS effects requiring intensive monitoring 2, 8
• Consider the possibility of co-ingestion with other substances, particularly in intentional overdoses, which may complicate the clinical picture 4, 5