Reflections on the Use of Perampanel in Epilepsy – Lessons from the Clinic and Real-world Evidence

Abstract

Optimal epilepsy management includes five important elements: rational treatment selection, efficacy, off-target effects, adherence and interactions and dosing issues. Perampanel (2-[2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl]benzonitrile; E2007) is the first potent, selective, orally-active non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist approved for the treatment of patients with epilepsy. Results from randomised controlled trials and real-world studies of refractory epilepsy populations treated with perampanel showed effective frequency reduction for both focal-onset seizures (without and with secondary generalisation) and for primary generalised tonic-clonic seizures. Perampanel therapeutic doses have been calculated to only inhibit a fraction of AMPA receptors, thereby to enable sufficient seizure control without substantial impairment of neurological function. Further investigation in special subpopulations of people with epilepsy, including the elderly and people with learning disability or psychiatric comorbidities, is warranted. With an average long half-life of 105 hours, perampanel may be more forgiving in circumstances of suboptimal adherence. Perampanel is not a strong inducer or inhibitor of cytochrome P450 enzymes, and dose adjustment is not always required for the elderly or for those with mild renal impairment.