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Open Access 01-12-2021 | Epilepsy | Research article

Perampanel as first add-on antiseizure medication: Italian consensus clinical practice statements

Authors: Paolo Bonanni, Antonio Gambardella, Paolo Tinuper, Benedetto Acone, Emilio Perucca, Giangennaro Coppola

Published in: BMC Neurology | Issue 1/2021

Abstract

Background

When use of a single antiseizure medication (ASM) fails to induce seizure remission, add-on therapy is justified. Perampanel (PER) is approved in Europe as adjunctive therapy for focal, focal to bilateral tonic-clonic seizures and generalized tonic-clonic seizures. Aim of the study was to establish whether PER is suitable for first add-on use.

Methods

A Delphi methodology was adopted to assess consensus on a list of 39 statements produced by an Expert Board of 5 epileptologists. Using an iterative process, statements were finalized by a Delphi Panel of 84 Italian pediatric and adult neurologists. Each statement was rated anonymously to determine level of agreement on a 9-point Likert scale. Consensus was established as agreement by at least 80% of the panelists. The relevance of each statement was also assessed on a 3-point scale.

Results

Consensus was achieved for 37 statements. Characteristics of PER considered to justify its use as first add-on include evidence of a positive impact on quality of life based on long term retention data, efficacy, tolerability, and ease of use; no worsening of cognitive functions and sleep quality; a low potential for drug interactions; a unique mechanism of action. Potential unfavorable factors are the need for a relatively slow dose titration; the potential occurrence of behavioral adverse effects; lack of information on safety when used in pregnancy; limited access to plasma PER levels.

Conclusion

Perampanel has many features which justify its use as a first add-on. Choice of an ASM as first add-on should be tailored to individual characteristics.

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Brodie MJ, Barry SJ, Bamagous GA, Norrie JD, Kwan P. Patterns of treatment response in newly diagnosed epilepsy. Neurology. 2012;78:1548–54. https://doi.org/10.1212/WNL.0b013e3182563b19.CrossRefPubMedPubMedCentral

Beghi E, Gatti G, Tonini C, Ben-Menachem E, Chadwick DW, Nikanorova M, et al. Adjunctive therapy versus alternative monotherapy in patients with partial epilepsy failing on a single drug: a multicentre, randomised, pragmatic controlled trial. Epilepsy Res. 2003;57:1–13. https://doi.org/10.1016/j.eplepsyres.2003.09.007.CrossRefPubMed

Semah F, Thomas P, Coulbaut S, Derambure P. Early add-on treatment vs alternative monotherapy in patients with partial epilepsy. Epileptic Disord. 2014;16:165–74. https://doi.org/10.1684/epd.2014.0650.CrossRefPubMed

Gambardella A, Tinuper P, Acone B, Bonanni P, Coppola G, Perucca E (2021) Selection of antiseizure medications for first add-on use: a consensus paper. Epilepsy Behav. In press.

Njuangang S, Liyanage C, Akintoye A. Application of the Delphi technique in healthcare maintenance. Int J Health Care Qual Assur. 2017;30:737–54. https://doi.org/10.1108/IJHCQA-02-2017-0042.CrossRefPubMed

Cretin B, Hirsch E. Adjunctive antiepileptic drugs in adult epilepsy: how the first add-on could be the last. Expert Opin Pharmacother. 2010;11:1053–67. https://doi.org/10.1517/14656561003709755 Review.CrossRefPubMed

Perucca E, Tomson T. The pharmacological treatment of epilepsy in adults. Lancet Neurol. 2011;10:446–56. https://doi.org/10.1016/S1474-4422(11)70047-3 PMID: 21511198 Review.CrossRefPubMed

Perucca P, Scheffer IE, Kiley M. The management of epilepsy in children and adults. Med J Aust. 2018;208:226–33. https://doi.org/10.5694/mja17.00951 Review.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;54:1481–9. https://doi.org/10.1111/epi.12212.CrossRefPubMed

10.

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;85:950–7. https://doi.org/10.1212/WNL.0000000000001930.CrossRefPubMedPubMedCentral

11.

Krauss GL, Perucca E, Kwan P, Ben-Menachem E, Wang XF, Shih JJ, et al. Final safety, tolerability, and seizure outcomes in patients with focal epilepsy treated with adjunctive perampanel for up to 4 years in an open-label extension of phase III randomized trials: study 307. Epilepsia. 2018;59:866–76. https://doi.org/10.1111/epi.14044.CrossRefPubMed

12.

Piña-Garza JE, Rosenfeld W, Saeki K, Villanueva V, Yoshinaga H, Patten A, et al. Efficacy and safety of adjunctive perampanel in adolescent patients with epilepsy: post hoc analysis of six randomized studies. Epilepsy Behav. 2020;104:106876. https://doi.org/10.1016/j.yebeh.2019.106876.CrossRefPubMed

13.

Rektor I, Krauss GL, Inoue Y, Kaneko S, Williams B, Patten A, et al. Assessment of the long-term efficacy and safety of adjunctive perampanel in tonic-clonic seizures: analysis of four open-label extension studies. Epilepsia. 2020;61:1491–502. https://doi.org/10.1111/epi.16573.CrossRefPubMedPubMedCentral

14.

Fogarasi A, Flamini R, Milh M, Phillips S, Yoshitomi S, Patten A, et al. Open-label study to investigate the safety and efficacy of adjunctive perampanel in pediatric patients (4 to <12 years) with inadequately controlled focal seizures or generalized tonic-clonic seizures. Epilepsia. 2020;61:125–37. https://doi.org/10.1111/epi.16413.CrossRefPubMedPubMedCentral

15.

Abril Jaramillo J, Estévez María JC, Girón Úbeda JM, Vega López Ó, Calzado Rivas ME, Pérez Díaz H, et al. Effectiveness and safety of perampanel as early add-on treatment in patients with epilepsy and focal seizures in the routine clinical practice: Spain prospective study (PERADON). Epilepsy Behav. 2020;102:106655. https://doi.org/10.1016/j.yebeh.2019.106655.CrossRefPubMed

16.

Santamarina E, Bertol V, Garayoa V, García-Gomara MJ, Garamendi-Ruiz I, Giner P, et al. Efficacy and tolerability of perampanel as a first add-on therapy with different anti-seizure drugs. Seizure. 2020;83:48–56. https://doi.org/10.1016/j.seizure.2020.09.026.CrossRefPubMed

17.

Bootsma HP, Ricker L, Hekster YA, Hulsman J, Lambrechts D, Majoie M, et al. The impact of side effects on long-term retention in three new antiepileptic drugs. Seizure. 2009;18:327–31.CrossRef

18.

Rosenfeld W, Fountain NB, Kaubrys G, Ben-Menachem E, McShea C, Isojarvi J, et al. Safety and efficacy of adjunctive lacosamide among patients with partial-onset seizures in a long-term open-label extension trial of up to 8 years. Epilepsy Behav. 2014;41:164–70. https://doi.org/10.1016/j.yebeh.2014.09.074 Clinical Trial.

19.

Brandt C, Wechsler RT, O'Brien TJ, Patten A, Malhotra M, Ngo LY, et al. Adjunctive perampanel and myoclonic and absence seizures: post hoc analysis of data from study 332 in patients with idiopathic generalized epilepsy. Seizure. 2020;80:115–23. https://doi.org/10.1016/j.seizure.2020.06.011.CrossRefPubMed

20.

Potschka H, Trinka E. Perampanel: does it have broad-spectrum potential? Epilepsia. 2019;60(Suppl 1):22–36. https://doi.org/10.1111/epi.14456 Review.CrossRefPubMed

21.

Lagae L. The need for broad spectrum and safe anti-epileptic drugs in childhood epilepsy. Acta Neurol Belg. 2009;109(3):167–70 Review.PubMed

22.

Glauser T, Laurenza L, Yang H, Williams B, Ma T, Fain R. Efficacy and tolerability of adjunct perampanel based on number of antiepileptic drugs at baseline and baseline predictors of efficacy: a phase III post-hoc analysis. Epilepsy Res. 2016;119:34–40. https://doi.org/10.1016/j.eplepsyres.2015.11.014 Clinical Trial.CrossRefPubMed

23.

Steinhoff BJ, Patten A, Williams B, Malhotra M. Efficacy and safety of adjunctive perampanel 4 mg/d for the treatment of focal seizures: a pooled post hoc analysis of four randomized, double-blind, phase III studies. Epilepsia. 2020;61:278–86. https://doi.org/10.1111/epi.16428 Epub 2020 Jan 16. Clinical Trial.CrossRefPubMedPubMedCentral

24.

Ko D, Yang H, Williams B, Xing D, Laurenza A. Perampanel in the treatment of partial seizures: time to onset and duration of most common adverse events from pooled phase III and extension studies. Epilepsy Behav. 2015;48:45–52. https://doi.org/10.1016/j.yebeh.2015.05.020 Clinical Trial.CrossRefPubMed

25.

Villanueva V, Garcés M, López-González 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.CrossRef

26.

Hasegawa N, Tohyama J. Positive and negative effects of perampanel treatment on psychiatric and behavioral symptoms in adult patients with epilepsy. Epilepsy Behav. 2021;17:107515. https://doi.org/10.1016/j.yebeh.2020.107515.CrossRef

27.

Deleo F, Quintas R, Turner K, Didato G, Zambrelli E, Pappalardo I, et al. The impact of perampanel treatment on quality of life and psychiatric symptoms in patients with drug-resistant focal epilepsy: an observational study in Italy. Epilepsy Behav. 2019;99:106391. https://doi.org/10.1016/j.yebeh.2019.06.034.CrossRefPubMed

28.

Meador KJ, Yang H, Piña-Garza JE, Laurenza A, Kumar D, Wesnes KA. Cognitive effects of adjunctive perampanel for partial-onset seizures: a randomized trial. Epilepsia. 2016;57:243–51. https://doi.org/10.1111/epi.13279 Clinical Trial.CrossRefPubMedPubMedCentral

29.

Piña-Garza JE, Lagae L, Villanueva V, Renfroe JB, Laurenza A, Williams B, et al. Long-term effects of adjunctive perampanel on cognition in adolescents with partial seizures. Epilepsy Behav. 2018;83:50–8. https://doi.org/10.1016/j.yebeh.2018.03.029 Clinical Trial.CrossRefPubMed

30.

Operto FF, Pastorino GMG, Mazza R, Di Bonaventura C, Matricardi S, Verrotti A, et al. Perampanel tolerability in children and adolescents with focal epilepsy: effects on behavior and executive functions. Epilepsy Behav. 2020;103:106879. https://doi.org/10.1016/j.yebeh.2019.106879.CrossRefPubMed

31.

Ahn SJ, Kim TJ, Cha KS, Jun JS, Byun JI, Shin YW, et al. Effects of perampanel on cognition and quantitative electroencephalography in patients with epilepsy. Epilepsy Behav. 2021;115:107514. https://doi.org/10.1016/j.yebeh.2020.107514.CrossRefPubMed

32.

Rocamora R, Álvarez I, Chavarría B, Principe A. Perampanel effect on sleep architecture in patients with epilepsy. Seizure. 2020;76:137–42. https://doi.org/10.1016/j.seizure.2020.01.021.CrossRefPubMed

33.

Yang H, Laurenza L, Williams B, Patten A, Hussein Z, Ferry J. Lack of effect of perampanel on QT interval duration: results from a thorough QT analysis and pooled partial seizure phase III clinical trials. Epilepsy Res. 2015;114:122–30. https://doi.org/10.1016/j.eplepsyres.2015.04.010 Clinical Trial.CrossRefPubMed

34.

Vazquez B, Tomson T, Dobrinsky C, Schuck E, O'Brien TJ. Perampanel and pregnancy. Epilepsia. 2021;62:698–708. https://doi.org/10.1111/epi.16821.CrossRefPubMedPubMedCentral

35.

Franco V, Crema F, Iudice A, Zaccara G, Grillo E. Novel treatment options for epilepsy: focus on perampanel. Pharmacol Res. 2013;70:35–40. https://doi.org/10.1016/j.phrs.2012.12.006.CrossRefPubMed

36.

Gidal BE, Ferry J, Majid O, Hussein Z. Concentration-effect relationships with perampanel in patients with pharmacoresistant partial-onset seizures. Epilepsia. 2013;54:1490–7. https://doi.org/10.1111/epi.12240.CrossRefPubMed

37.

Gidal BE, Laurenza A, Hussein Z, Yang H, Fain R, Edelstein J, et al. Perampanel efficacy and tolerability with enzyme-inducing AEDs in patients with epilepsy. Neurology. 2015;84:1972–80. https://doi.org/10.1212/WNL.0000000000001558.CrossRefPubMedPubMedCentral

38.

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. https://doi.org/10.1016/j.eplepsyres.2016.08.025 Clinical Trial.CrossRefPubMed

39.

European Medicines Agency (EMA). Perampanel (Fycompa): Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/fycompa-epar-product-information_en.pdf (Last Accessed 1 Oct 2021).

40.

Food and Drug Administration. Fycompa – Full Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202834s016,208277s004lbl.pdf (Last Accessed 1 Oct 2021).

41.

Villanueva V, Montoya J, Castillo A, Mauri-Llerda JÁ, Giner P, López-González FJ, et al. Perampanel in routine clinical use in idiopathic generalized epilepsy: the 12-month GENERAL study. Epilepsia. 2018;59:1740–52. https://doi.org/10.1111/epi.14522.CrossRefPubMed

42.

Di Bonaventura C, Labate A, Maschio M, Meletti S, Russo E. AMPA receptors and perampanel behind selected epilepsies: current evidence and future perspectives. Expert Opin Pharmacother. 2017;18:1751–64. https://doi.org/10.1080/14656566.2017.1392509.CrossRefPubMed

43.

Deckers CL, Czuczwar SJ, Hekster YA, Keyser A, Kubova H, Meinardi H, et al. Selection of antiepileptic drug polytherapy based on mechanisms of action: the evidence reviewed. Epilepsia. 2000;41:1364–74. https://doi.org/10.1111/j.1528-1157.2000.tb00111.x.CrossRefPubMed

44.

Brodie MJ, Covanis A, Gil-Nagel A, Lerche H, Perucca E, Sills GJ, et al. Antiepileptic drug therapy: does mechanism of action matter? Epilepsy Behav. 2011;21:331–41. https://doi.org/10.1016/j.yebeh.2011.05.025.CrossRefPubMed

45.

Perucca E. The pharmacology of new antiepileptic drugs: does a novel mechanism of action really matter? CNS Drugs. 2011;25:907–12. https://doi.org/10.2165/11587900-000000000-00000.CrossRefPubMed

46.

Verrotti A, Lattanzi S, Brigo F, Zaccara G. Pharmacodynamic interactions of antiepileptic drugs: from bench to clinical practice. Epilepsy Behav. 2020;104:106939. https://doi.org/10.1016/j.yebeh.2020.106939.CrossRefPubMed

47.

Suzuki H, Mikuni N, Ohnishi H, Yokoyama R, Enatsu R, Ochi S. Forgetting to take antiseizure medications is associated with focal to bilateral tonic-clonic seizures, as revealed by a cross-sectional study. PLoS One. 2020;15:e0240082. https://doi.org/10.1371/journal.pone.0240082.CrossRefPubMedPubMedCentral

48.

Faught E, Duh MS, Weiner JR, Guérin A, Cunnington MC. Nonadherence to antiepileptic drugs and increased mortality: findings from the RANSOM study. Neurology. 2008;71:1572–8. https://doi.org/10.1212/01.wnl.0000319693.10338.b9.CrossRefPubMed

49.

Sveinsson O, Andersson T, Mattsson P, Carlsson S, Tomson T. Pharmacologic treatment and SUDEP risk: a nationwide, population-based, case-control study. Neurology. 2020;95:e2509–18. https://doi.org/10.1212/WNL.0000000000010874.CrossRefPubMedPubMedCentral

50.

Eatock J, Baker GA. Managing patient adherence and quality of life in epilepsy. Neuropsychiatr Dis Treat. 2007;3:117–31. https://doi.org/10.2147/nedt.2007.3.1.117.CrossRefPubMedPubMedCentral

Title: Perampanel as first add-on antiseizure medication: Italian consensus clinical practice statements
Authors: Paolo Bonanni
Antonio Gambardella
Paolo Tinuper
Benedetto Acone
Emilio Perucca
Giangennaro Coppola
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Epilepsy
Perampanel
Published in: BMC Neurology / Issue 1/2021
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/s12883-021-02450-y

2024 ASCO Annual Meeting

Springer Medicine

Perampanel as first add-on antiseizure medication: Italian consensus clinical practice statements

Abstract

Background

Methods

Results

Conclusion

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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