J Clin Neurol.  2018 Jul;14(3):296-302. 10.3988/jcn.2018.14.3.296.

Adverse Events During Perampanel Adjunctive Therapy in Intractable Epilepsy

• Youn SE
• Kim SH
• Ko A
• Lee SH
• Lee YM
• Kang HC
• Lee JS
• Kim HD

• KMID: 2415044
• DOI: http://doi.org/10.3988/jcn.2018.14.3.296

Abstract

BACKGROUND AND PURPOSE
Perampanel is the first α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-receptor antagonist developed to treat epilepsy. The effects of either rapid or slow dose titration on adverse events remain to be elucidated.
METHODS
Eighty-five patients received perampanel between March 2016 and August 2016. Patients were divided into two groups according to their dosing schedule: rapid dose titration (2-mg increments at intervals of 1 to 2 weeks) and slow dose titration (2-mg increments at intervals of at least 3 weeks). Seizure frequency and adverse events were analyzed over 3 months.
RESULTS
Adverse events were reported by 47 (58%) of the 81 patients analyzed, with 12 (15%) patients discontinuing perampanel due to adverse events. Common adverse events included dizziness (n=30, 37%), aggressive mood and behavior (n=19, 24%), gait disturbance (n=16, 20%), and sleep problems (n=10, 12.4%). The overall adverse events were similar in the slow-titration group (38 of 61 patients) and the rapid-titration group (8 of 20 patients, p=0.081). However, none of the 20 patients in the slow-titration group experienced gait disturbance, compared with 16 of the 61 patients in the rapid-titration group (p=0.009), while appetite change was experienced by 4 patients in the slow-titration group but only 1 in the rapid-titration group (p=0.003). No relationship was noted between adverse events and the maximum dose of perampanel (p=0.116). Sex differences were observed, with the response to perampanel being better and the rate of adverse events being higher in females (p=0.015 and p=0.046, respectively).
CONCLUSIONS
Slow titration of perampanel may reduce perampanel-related adverse events.

Keyword

perampanel; drug-resistant epilepsy; antiepileptic drug; α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid

MeSH Terms

Appetite
Appointments and Schedules
Dizziness
Drug Resistant Epilepsy*
Epilepsy
Female
Gait
Humans
Seizures
Sex Characteristics

Figure

• 

  Fig. 1 Numbers of patients who experienced adverse events. The most-common adverse events were dizziness and somnolence, followed by aggressive mood and behavior. Other adverse events included excessive sputum production, drooling, dysphagia, nausea, memory impairment, and bizarre feeling.

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  Fig. 2 Three-month seizure outcomes and occurrence of adverse events for different maximum doses of perampanel. A: The maximum doses were 2 and 4 mg in 7 patients. Two patients achieved seizure freedom when taking perampanel at the relatively low dose of 4 mg. The maximum doses were 6, 8, and 10 mg in more than two-thirds (56 of 81 patients) of patients. The rates of responders and seizure freedom were high for doses between 6 and 10 mg. The perampanel dose was increased to 12 mg when their seizures persisted, and no serious adverse events occurred. However, the rates of responders and seizure freedom were significantly low at a dose of 12 mg. B: Five patients stopped taking perampanel at low doses (e.g., 2 or 4 mg) due to adverse events. Only one patient stopped taking perampanel at 12 mg. Two patients who stopped at a dose of 2 mg experienced severe dizziness, and three patients who stopped at a dose of 4 mg reported experiencing multiple side effects including gait disturbance, dizziness, and aggressive behavior.

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