Analysis of pooled phase III trials of adjunctive perampanel for epilepsy: Impact of mechanism of action and pharmacokinetics on clinical outcomes

• Published in: Epilepsy research Vol. 117; pp. 117 - 124
• Main Authors: Kwan, Patrick, Brodie, Martin J, Laurenza, Antonio, FitzGibbon, Hannah, Gidal, Barry E
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-11-2015
• Subjects: Adolescent; Adult; Aged; Anticonvulsants - pharmacokinetics; Anticonvulsants - therapeutic use; Antiepileptic drugs; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Enzyme induction; Epilepsy - drug therapy; Female; Humans; Male; Middle Aged; Neurology; Partial-onset seizures; Perampanel; Pyridones - pharmacokinetics; Pyridones - therapeutic use; Sodium channel blockers; Treatment Outcome; Young Adult; AED; AMPA; AE; antiepileptic drug; treatment-emergent adverse event; adverse event; Partial-onset seizures; cytochrome P450; α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid; EIAED; sodium channel blocker; TEAE; SCB; Perampanel; Enzyme induction; enzyme-inducing antiepileptic drug; Sodium channel blockers; CYP; Antiepileptic drugs
• ISSN: 0920-1211; 1872-6844
• DOI: 10.1016/j.eplepsyres.2015.09.002

Highlights • Perampanel efficacy may be reduced by concomitant enzyme-inducing AEDs (EIAEDs). • This is due to greater CYP3A4 activity and reduced plasma perampanel concentrations. • Perampanel efficacy appears to be unaffected by the use of concomitant non-EIAED sodium channel blockers. • Magnitude of seizure reduction was also lower in the presence of multiple AEDs. • With careful titration perampanel may be combined with a range of AEDs for epilepsy.