A monograph on Perampanel

Abstract

Perampanel is a non-competitive antagonist at the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid) subtype of ionotropic glutamate receptor. It is approved as an adjunctive therapy in focal epilepsy with or without secondarily generalised seizures in patients aged >12 years. This in-depth review describes the structure, mechanism of action, pharmacokinetic profile, indications, dosage and efficacy, contraindications, possible drug interactions, adverse effect profile and its management with regards to Perampanel. It is one of the latest additions in the therapeutic armamentarium of an epileptologist being useful in focal as well as generalised epilepsies as an add-on. It has shown high rates of efficacy and a relatively good tolerability. Slow dose titration, patient education and bed time dosing along with downtitration of medications which may aggravate Perampanel associated adverse events improves the patients’ compliance and quality of life.

Keywords

Adjunctive therapy - AMPA antagonist - Focal epilepsy

• References

• 1 Rheims S, Rylvin P. Profile of perampanel and its potential in the treatment of partial onset seizures. Neuropsychiatr Dis Treat 9 2013; 629-637
• 2 Kwan P, Schachter SC, Brodie MJ. Drug-resistant epilepsy. N Engl J Med 365 2011; 919-926
• 3 Stephen LJ, Brodie MJ. Antiepileptic drug monotherapy versus polytherapy: pursuing seizure freedom and tolerability in adults. Curr Opin Neurol 25 2012; 164-172
• 4 Faught E. Antiepileptic drug trials: the view from the clinic. Epileptic Disord 14 2012; 114-123
• 5 Marson AG, Williamson PR. Interpreting regulatory trials in epilepsy. Curr Opin Neurol 22 2009; 167-173
• 6 Brodie MJ. Meta-analyses of antiepileptic drugs for refractory partial (focal) epilepsy: an observation. Br J Clin Pharmacol 76 2013; 630-631
• 7 Brodie MJ, Kelly K, Stephen LJ. Prospective audits with newer antiepileptic drugs in focal epilepsy: insights into population responses?. Epilepsy Behav 31 2014; 73-76
• 8 Wedzony K, Fijal K, Mackowiak M, Chocyk A, Zajaczkowski W. Impact of postnatal blockade of N-methyl-d-aspartate receptors on rat behavior: a search for a new developmental model of schizophrenia. Neuroscience 153 (04) 2008; 1370-1379
• 9 Nabeshima T, Mouri A, Murai R, Noda Y. Animal model of schizophrenia: dysfunction of NMDA receptor-signaling in mice following withdrawal from repeated administration of phencyclidine. Ann N Y Acad Sci 1086 2006; 160-168
• 10 French JA, Krauss GL, Biton V. et al. Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. Neurology 79 (06) 2012; 589-596
• 11 Krauss GL, Serratosa JM, Villanueva V. et al. Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures. Neurology 78 (18) 2012; 1408-1415
• 12 Steinhoff BJ, Ben-Menachem E, Ryvlin P. et al. Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: a pooled analysis of three phase III studies. Epilepsia 54 2013; 1481-1489
• 13 Chen CY, Matt L, Hell JW, Rogawski MA. Perampanel inhibition of AMPA receptor currents in cultured hippocampal neurons. PLOS ONE 9 (09) 2014; e108021 10.1371/journal.pone.0108021
• 14 Hanada T, Hashizume Y, Takenaka O. et al. Perampanel: a novel, orally active, noncompetitive AMPA-receptor antagonist that reduces seizure activity in rodent models of epilepsy. Epilepsia 52 July (7) 2011; 1331-1340
• 15 Krauss GL, Perucca E, Ben-Menachem E. et al. Perampanel, a selective, noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, as adjunctive therapy for refractory partial-onset seizures: interim results from phase 3, extension study 307. Epilepsia 54 January (1) 2013; 126-134
• 16 Krauss GL, Perucca E, Ben-Menachem E, Kwan P, Shih JJ, Clément JF. Longterm safety of perampanel and seizure outcomes in refractory partial-onset seizures and secondarily generalized seizures: results from phase III extension study 307. Epilepsia 55 2014; 1058-1068
• 17 Khan N, Shah D, Tongbram V, Verdian L, Hawkins N. The efficacy and tolerability of perampanel and other recently approved anti-epileptic drugs for the treatment of refractory partial onset seizure: a systematic review and Bayesian network meta-analysis. Curr Med Res Opin 29 2013; 1001-1013
• 18 Ettinger A, Lopresti A, Yang H. et al. Psychiatric and behavioural adverse events in randomized clinical studies of the noncompetitive AMPA receptor antagonist perampanel. Epilepsia 56 2015; 1252-1263
• 19 Steinhoff BJ, Laurenza A, Yang H, Satlin A. Safety profile of perampanel as an adjunctive treatment for partial onset seizures. J Symptoms Signs 3 2014; 64-70
• 20 Sirven JI, Fife TD, Wingerchuk DM, Drazkowski JF. Second-generation antiepileptic drugs’ impact on balance: a meta-analysis. Mayo Clin Proc 82 2007; 40-47