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Published in: Italian Journal of Pediatrics 1/2017

Open Access 01-12-2017 | Review

Current role of perampanel in pediatric epilepsy

Authors: Paola De Liso, Romina Moavero, Giangennaro Coppola, Paolo Curatolo, Raffaella Cusmai, Giovambattista De Sarro, Emilio Franzoni, Federico Vigevano, Alberto Verrotti

Published in: Italian Journal of Pediatrics | Issue 1/2017

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Abstract

Perampanel is among the latest AEDs approved, indicated for the treatment of partial-onset seizures with or without secondary generalization, and for primary generalized tonic-clonic seizures, in patients aged 12 years and older. This paper summarizes the clinical recommendations on the current role of perampanel in the treatment of pediatric epilepsies and future directions for research. The optimal dosage should be comprised between 4 and 12 mg/day, with 8 mg/day being the most common dosage used. The rate and severity of adverse events, including psychiatric symptoms, can be decreased by starting at low doses, and titrating slowly. Overall, perampanel presents an acceptable risk/benefit ratio, but special caution should be made to the risk of seizure aggravation and behavioral problems. The favorable cognitive profile, the ease of use of the titration scheme and the once-daily formulation offer advantage over other AEDs and make this drug particularly suitable for adolescent population. Perampanel is a welcome addition to the armamentarium of the existing AEDs, as it represents a new approach in the management of epilepsy, with a novel mechanism of action and a potential to have a considerable impact on the treatment of adolescents with epilepsy.
Literature
1.
go back to reference Camfield P, Camfield C. Incidence, prevalence and aetiology of seizures and epilepsy in children. Epileptic Disord: Int Epilepsy J Videotape. 2015;17(2):117–23. Camfield P, Camfield C. Incidence, prevalence and aetiology of seizures and epilepsy in children. Epileptic Disord: Int Epilepsy J Videotape. 2015;17(2):117–23.
2.
go back to reference Zuberi SM, Symonds JD. Update on diagnosis and management of childhood epilepsies. J Pediatr. 2015;91(6 Suppl 1):S67–77.CrossRef Zuberi SM, Symonds JD. Update on diagnosis and management of childhood epilepsies. J Pediatr. 2015;91(6 Suppl 1):S67–77.CrossRef
3.
go back to reference Hanada T, Hashizume Y, Tokuhara N, Takenaka O, Kohmura N, Ogasawara A, et al. Perampanel: a novel, orally active, noncompetitive AMPA-receptor antagonist that reduces seizure activity in rodent models of epilepsy. Epilepsia. 2011;52(7):1331–40.CrossRefPubMed Hanada T, Hashizume Y, Tokuhara N, Takenaka O, Kohmura N, Ogasawara A, et al. Perampanel: a novel, orally active, noncompetitive AMPA-receptor antagonist that reduces seizure activity in rodent models of epilepsy. Epilepsia. 2011;52(7):1331–40.CrossRefPubMed
4.
go back to reference Rogawski MA, Hanada T. Preclinical pharmacology of perampanel, a selective non-competitive AMPA receptor antagonist. Acta Neurol Scand Suppl. 2013;197:19–24.CrossRef Rogawski MA, Hanada T. Preclinical pharmacology of perampanel, a selective non-competitive AMPA receptor antagonist. Acta Neurol Scand Suppl. 2013;197:19–24.CrossRef
5.
go back to reference Rogawski MA. AMPA receptors as a molecular target in epilepsy therapy. Acta neurologica Scandinavica Supplementum. 2013(197):9-18. Rogawski MA. AMPA receptors as a molecular target in epilepsy therapy. Acta neurologica Scandinavica Supplementum. 2013(197):9-18.
6.
go back to reference Citraro R, Aiello R, Franco V, De Sarro G, Russo E. Targeting alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors in epilepsy. Expert Opin Ther Targets. 2014;18(3):319–34.CrossRefPubMed Citraro R, Aiello R, Franco V, De Sarro G, Russo E. Targeting alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors in epilepsy. Expert Opin Ther Targets. 2014;18(3):319–34.CrossRefPubMed
7.
go back to reference Hanada T, Ido K, Kosasa T. Effect of perampanel, a novel AMPA antagonist, on benzodiazepine-resistant status epilepticus in a lithium-pilocarpine rat model. Pharmacol res Perspect. 2014;2(5):e00063.CrossRefPubMedPubMedCentral Hanada T, Ido K, Kosasa T. Effect of perampanel, a novel AMPA antagonist, on benzodiazepine-resistant status epilepticus in a lithium-pilocarpine rat model. Pharmacol res Perspect. 2014;2(5):e00063.CrossRefPubMedPubMedCentral
8.
go back to reference Bialer M, Johannessen SI, Levy RH, Perucca E, Tomson T, White HS. Progress report on new antiepileptic drugs: a summary of the tenth Eilat conference (EILAT X). Epilepsy res. 2010;92(2-3):89–124.CrossRefPubMed Bialer M, Johannessen SI, Levy RH, Perucca E, Tomson T, White HS. Progress report on new antiepileptic drugs: a summary of the tenth Eilat conference (EILAT X). Epilepsy res. 2010;92(2-3):89–124.CrossRefPubMed
9.
go back to reference Patsalos PN. The clinical pharmacology profile of the new antiepileptic drug perampanel: a novel noncompetitive AMPA receptor antagonist. Epilepsia. 2015;56(1):12–27.CrossRefPubMed Patsalos PN. The clinical pharmacology profile of the new antiepileptic drug perampanel: a novel noncompetitive AMPA receptor antagonist. Epilepsia. 2015;56(1):12–27.CrossRefPubMed
10.
go back to reference Franco V, Iudice A, Grillo E, Citraro R, De Sarro G, Russo E. Perspective on the use of perampanel and intravenous carbamazepine for generalized seizures. Expert Opin Pharmacother. 2014;15(5):637–44.CrossRefPubMed Franco V, Iudice A, Grillo E, Citraro R, De Sarro G, Russo E. Perspective on the use of perampanel and intravenous carbamazepine for generalized seizures. Expert Opin Pharmacother. 2014;15(5):637–44.CrossRefPubMed
11.
go back to reference Franco V, Marchiselli R, Fattore C, Tartara E, De Sarro G, Russo E, et al. Development and validation of an HPLC-UV assay for the therapeutic monitoring of the new antiepileptic drug Perampanel in human plasma. Ther Drug Monit. 2016;38(6):744–50.CrossRefPubMed Franco V, Marchiselli R, Fattore C, Tartara E, De Sarro G, Russo E, et al. Development and validation of an HPLC-UV assay for the therapeutic monitoring of the new antiepileptic drug Perampanel in human plasma. Ther Drug Monit. 2016;38(6):744–50.CrossRefPubMed
12.
go back to reference Villanueva V, Majid O, Nabangchang C, Yang H, Laurenza A, Ferry J, et al. Pharmacokinetics, exposure-cognition, and exposure-efficacy relationships of perampanel in adolescents with inadequately controlled partial-onset seizures. Epilepsy res. 2016;127:126–34.CrossRefPubMed Villanueva V, Majid O, Nabangchang C, Yang H, Laurenza A, Ferry J, et al. Pharmacokinetics, exposure-cognition, and exposure-efficacy relationships of perampanel in adolescents with inadequately controlled partial-onset seizures. Epilepsy res. 2016;127:126–34.CrossRefPubMed
13.
go back to reference French JA, Krauss GL, Biton V, Squillacote D, Yang H, Laurenza A, et al. Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. Neurology. 2012;79(6):589–96.CrossRefPubMedPubMedCentral French JA, Krauss GL, Biton V, Squillacote D, Yang H, Laurenza A, et al. Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. Neurology. 2012;79(6):589–96.CrossRefPubMedPubMedCentral
14.
go back to reference Krauss GL, Serratosa JM, Villanueva V, Endziniene M, Hong Z, French J, et al. Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures. Neurology. 2012;78(18):1408–15.CrossRefPubMed Krauss GL, Serratosa JM, Villanueva V, Endziniene M, Hong Z, French J, et al. Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures. Neurology. 2012;78(18):1408–15.CrossRefPubMed
15.
go back to reference French JA, Krauss GL, Steinhoff BJ, Squillacote D, Yang H, Kumar D, et al. Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: results of randomized global phase III study 305. Epilepsia. 2013;54(1):117–25.CrossRefPubMed French JA, Krauss GL, Steinhoff BJ, Squillacote D, Yang H, Kumar D, et al. Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: results of randomized global phase III study 305. Epilepsia. 2013;54(1):117–25.CrossRefPubMed
16.
go back to reference Krauss GL, Perucca E, Ben-Menachem E, Kwan P, Shih JJ, Squillacote D, et al. Perampanel, a selective, noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, as adjunctive therapy for refractory partial-onset seizures: interim results from phase III, extension study 307. Epilepsia. 2013;54(1):126–34.CrossRefPubMed Krauss GL, Perucca E, Ben-Menachem E, Kwan P, Shih JJ, Squillacote D, et al. Perampanel, a selective, noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, as adjunctive therapy for refractory partial-onset seizures: interim results from phase III, extension study 307. Epilepsia. 2013;54(1):126–34.CrossRefPubMed
17.
go back to reference Rosenfeld W, Conry J, Lagae L, Rozentals G, Yang H, Fain R, et al. Efficacy and safety of perampanel in adolescent patients with drug-resistant partial seizures in three double-blind, placebo-controlled, phase III randomized clinical studies and a combined extension study. Eur J Paediatr Neurol. 2015;19(4):435–45.CrossRefPubMed Rosenfeld W, Conry J, Lagae L, Rozentals G, Yang H, Fain R, et al. Efficacy and safety of perampanel in adolescent patients with drug-resistant partial seizures in three double-blind, placebo-controlled, phase III randomized clinical studies and a combined extension study. Eur J Paediatr Neurol. 2015;19(4):435–45.CrossRefPubMed
18.
go back to reference Lagae L, Villanueva V, Meador KJ, Bagul M, Laurenza A, Kumar D, et al. Adjunctive perampanel in adolescents with inadequately controlled partial-onset seizures: a randomized study evaluating behavior, efficacy, and safety. Epilepsia. 2016;57(7):1120–9.CrossRefPubMed Lagae L, Villanueva V, Meador KJ, Bagul M, Laurenza A, Kumar D, et al. Adjunctive perampanel in adolescents with inadequately controlled partial-onset seizures: a randomized study evaluating behavior, efficacy, and safety. Epilepsia. 2016;57(7):1120–9.CrossRefPubMed
19.
go back to reference Biro A, Stephani U, Tarallo T, Bast T, Schlachter K, Fleger M, et al. Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies: first experiences. Neuropediatrics. 2015;46(2):110–6.CrossRefPubMed Biro A, Stephani U, Tarallo T, Bast T, Schlachter K, Fleger M, et al. Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies: first experiences. Neuropediatrics. 2015;46(2):110–6.CrossRefPubMed
20.
go back to reference De Liso P, Vigevano F, Specchio N, De Palma L, Bonanni P, Osanni E, et al. Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies-an Italian observational multicenter study. Epilepsy res. 2016;127:93–100.CrossRefPubMed De Liso P, Vigevano F, Specchio N, De Palma L, Bonanni P, Osanni E, et al. Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies-an Italian observational multicenter study. Epilepsy res. 2016;127:93–100.CrossRefPubMed
21.
go back to reference French JA, Krauss GL, Wechsler RT, Wang XF, DiVentura B, Brandt C, et al. Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy a randomized trial. Neurology. 2015;85(11):950–7.CrossRefPubMedPubMedCentral French JA, Krauss GL, Wechsler RT, Wang XF, DiVentura B, Brandt C, et al. Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy a randomized trial. Neurology. 2015;85(11):950–7.CrossRefPubMedPubMedCentral
22.
go back to reference Schorlemmer K, Bauer S, Belke M, Hermsen A, Klein KM, Reif PS, et al. Sustained seizure remission on perampanel in progressive myoclonic epilepsy (Lafora disease). Epilepsy Behav Case Rep. 2013;1:118–21.CrossRefPubMedPubMedCentral Schorlemmer K, Bauer S, Belke M, Hermsen A, Klein KM, Reif PS, et al. Sustained seizure remission on perampanel in progressive myoclonic epilepsy (Lafora disease). Epilepsy Behav Case Rep. 2013;1:118–21.CrossRefPubMedPubMedCentral
23.
go back to reference Dirani M, Nasreddine W, Abdulla F, Beydoun A. Seizure control and improvement of neurological dysfunction in Lafora disease with perampanel. Epilepsy Behav Case Rep. 2014;2:164–6.CrossRefPubMedPubMedCentral Dirani M, Nasreddine W, Abdulla F, Beydoun A. Seizure control and improvement of neurological dysfunction in Lafora disease with perampanel. Epilepsy Behav Case Rep. 2014;2:164–6.CrossRefPubMedPubMedCentral
24.
go back to reference Goldsmith D, Minassian BA. Efficacy and tolerability of perampanel in ten patients with Lafora disease. Epilepsy Behav. 2016;62:132–5.CrossRefPubMed Goldsmith D, Minassian BA. Efficacy and tolerability of perampanel in ten patients with Lafora disease. Epilepsy Behav. 2016;62:132–5.CrossRefPubMed
25.
go back to reference Steinhoff BJ, Ben-Menachem E, Ryvlin P, Shorvon S, Kramer L, Satlin A, et al. Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: a pooled analysis of three phase III studies. Epilepsia. 2013;54(8):1481–9.CrossRefPubMed Steinhoff BJ, Ben-Menachem E, Ryvlin P, Shorvon S, Kramer L, Satlin A, et al. Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: a pooled analysis of three phase III studies. Epilepsia. 2013;54(8):1481–9.CrossRefPubMed
26.
go back to reference Heyman E, Lahat E, Levin N, Epstein O, Lazinger M, Berkovitch M, et al. Tolerability and efficacy of perampanel in children with refractory epilepsy. Dev Med Child Neurol. 2016;59:441–44. Heyman E, Lahat E, Levin N, Epstein O, Lazinger M, Berkovitch M, et al. Tolerability and efficacy of perampanel in children with refractory epilepsy. Dev Med Child Neurol. 2016;59:441–44.
27.
go back to reference Juhl S, Rubboli G. Perampanel as add-on treatment in refractory focal epilepsy. Dianalund Experience Acta Neurol Scand. 2016;134(5):374–7.CrossRefPubMed Juhl S, Rubboli G. Perampanel as add-on treatment in refractory focal epilepsy. Dianalund Experience Acta Neurol Scand. 2016;134(5):374–7.CrossRefPubMed
28.
go back to reference Huber B, Schmid G. A two-year retrospective evaluation of perampanel in patients with highly drug-resistant epilepsy and cognitive impairment. Epilepsy Behav. 2017;66:74–9.CrossRefPubMed Huber B, Schmid G. A two-year retrospective evaluation of perampanel in patients with highly drug-resistant epilepsy and cognitive impairment. Epilepsy Behav. 2017;66:74–9.CrossRefPubMed
29.
go back to reference Snoeijen-Schouwenaars FM, van Ool JS, Tan IY, Schelhaas HJ, Majoie MH. Evaluation of perampanel in patients with intellectual disability and epilepsy. Epilepsy Behav. 2017;66:64–7.CrossRefPubMed Snoeijen-Schouwenaars FM, van Ool JS, Tan IY, Schelhaas HJ, Majoie MH. Evaluation of perampanel in patients with intellectual disability and epilepsy. Epilepsy Behav. 2017;66:64–7.CrossRefPubMed
30.
go back to reference Garamendi-Ruiz I, Garcia-Garcia ME, Bertol-Alegre V, Mauri-Llerda JA, Garcia-Morales I, Garayoa-Irigoyen V, et al. One-year clinical experience of perampanel in Spain: a multicentre study of efficacy and tolerability. Epileptic Disord. 2016;18(2):173–80.PubMed Garamendi-Ruiz I, Garcia-Garcia ME, Bertol-Alegre V, Mauri-Llerda JA, Garcia-Morales I, Garayoa-Irigoyen V, et al. One-year clinical experience of perampanel in Spain: a multicentre study of efficacy and tolerability. Epileptic Disord. 2016;18(2):173–80.PubMed
31.
go back to reference Meador KJ, Yang H, Pina-Garza JE, Laurenza A, Kumar D, Wesnes KA. Cognitive effects of adjunctive perampanel for partial-onset seizures: a randomized trial. Epilepsia. 2016;57(2):243–51.CrossRefPubMedPubMedCentral Meador KJ, Yang H, Pina-Garza JE, Laurenza A, Kumar D, Wesnes KA. Cognitive effects of adjunctive perampanel for partial-onset seizures: a randomized trial. Epilepsia. 2016;57(2):243–51.CrossRefPubMedPubMedCentral
32.
go back to reference Ettinger AB, LoPresti A, Yang H, Williams B, Zhou S, Fain R, et al. Psychiatric and behavioral adverse events in randomized clinical studies of the noncompetitive AMPA receptor antagonist perampanel. Epilepsia. 2015;56(8):1252–63.CrossRefPubMedPubMedCentral Ettinger AB, LoPresti A, Yang H, Williams B, Zhou S, Fain R, et al. Psychiatric and behavioral adverse events in randomized clinical studies of the noncompetitive AMPA receptor antagonist perampanel. Epilepsia. 2015;56(8):1252–63.CrossRefPubMedPubMedCentral
33.
go back to reference Villanueva V, Garces M, Lopez-Gonzalez FJ, Rodriguez-Osorio X, Toledo M, Salas-Puig J, et al. Safety, efficacy and outcome-related factors of perampanel over 12 months in a real-world setting: the FYDATA study. Epilepsy res. 2016;126:201–10.CrossRefPubMed Villanueva V, Garces M, Lopez-Gonzalez FJ, Rodriguez-Osorio X, Toledo M, Salas-Puig J, et al. Safety, efficacy and outcome-related factors of perampanel over 12 months in a real-world setting: the FYDATA study. Epilepsy res. 2016;126:201–10.CrossRefPubMed
Metadata
Title
Current role of perampanel in pediatric epilepsy
Authors
Paola De Liso
Romina Moavero
Giangennaro Coppola
Paolo Curatolo
Raffaella Cusmai
Giovambattista De Sarro
Emilio Franzoni
Federico Vigevano
Alberto Verrotti
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Italian Journal of Pediatrics / Issue 1/2017
Electronic ISSN: 1824-7288
DOI
https://doi.org/10.1186/s13052-017-0368-6

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