Severe Perampanel Toxicity in a Pediatric Patient With Prolonged Symptoms

Perampanel is a new antiepileptic used to treat partial-onset seizures and generalized tonic-clonic seizures in people older than 12 years old. Perampanel is a selective, non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, with a prolonged half-life of approximately 105 hours. Few cases of significant toxicity have been reported, and effects in overdose are poorly understood.

This case describes a 20-month-old healthy female who ingested 8 mg of perampanel. She presented to a pediatric emergency department 1 hour after ingestion with ataxia, irritability, and somnolence. Vital signs were: heart rate 130 beats per minute, blood pressure 112/97 mmHg, temperature 99°F, respiratory rate 30 breaths per minute. She was admitted to the pediatric intensive care unit. During the hospitalization, she developed hypotension and bradycardia which improved with stimulation and fluid resuscitation. Intermittent bradycardia persisted for 32 hours after ingestion. Physical examination was notable for somnolence and truncal ataxia with irritability when aroused, all of which improved throughout the hospitalization. A quantitative level obtained on hospital day 3 (HD) was 750ng/ml. On HD 3 the patient was noted to be ataxic but otherwise had an age-appropriate neurologic examination. She was discharged on HD 4 with normal vital signs, return to baseline mental status, and baseline gait. The patient's cardiovascular, neurologic, and behavioral symptoms were attributed to perampanel toxicity. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS ?: Toxicity from a perampanel overdose is poorly understood both in adults and pediatric patients with significant cardiovascular, behavioral, and central nervous system abnormalities.