Efficacy and tolerability of perampanel as a first add-on therapy with different anti-seizure drugs

Santamarina, Estevo; Bertol, Vicente; Garayoa, Vanesa; García-Gomara, María José; Garamendi-Ruíz, Iñigo; Giner, P.; Aranzábal, Inés; Piera, Anna; Arcos, Carolina; Esteve, Patricia; Marinas, Ainhoa; García-Escrivá, A; Viloria-Alebesque, Alejandro; Loro, Fernando Ayuga; Tienda, A. Ponz de; Oliván, José Antonio Salvador; Bonet, Macarena; Dávila-González, Pablo; Sivera, Rafael; Molins, A; Sansa, Gemma; Roche, J; Martínez, Ana Belén; Monteagudo, Sandra; Casadevall, T

doi:10.1016/j.seizure.2020.09.026

Cited by 39 publications

(79 citation statements)

References 48 publications

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“…Since enzyme inducers may interfere with the metabolism of perampanel and reduce serum drug concentrations, our study confirmed the influence of EIASMs on PER efficacy. Unlike what other studies have shown ( 17 , 24 , 25 ), although subjects taking EIASMs with PER did have higher maintenance dose compared with those taking non-EIASMs, the effect of EIASMs on PER efficacy was not reduced. This difference may be due to demographic characteristics and pharmacokinetic characteristics of different races.…”

Section: Discussioncontrasting

confidence: 94%

Efficacy and Tolerability of Perampanel as Adjunctive Therapy in Chinese Patients With Focal-Onset Seizures: An Observational, Prospective Study

et al. 2021

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Purpose: To evaluate the efficacy and tolerability of adjunctive perampanel (PER) in Chinese patients with focal-onset seizures, with or without secondarily generalized tonic-clonic seizures.Methods: Fifty-six patients aged 14–72 years were recruited consecutively in this single-center prospective observational study. All patients received PER as add-on treatment on the basis of clinical judgment. Seizure frequency, adverse events (AEs), and retention rates were obtained at 3 and 6 months after PER introduction.Results: The overall response rates were 60 and 71.1% after 3 and 6 months, respectively, and the freedom of seizures at the same points were reached in 8 and 15.8%. The retention rates were 89.3% at the 3-month follow-up and 67.9% at the 6-month follow-up. The overall incidence of adverse events was 55.4%. The leading reported AEs were dizziness (39.3%) and somnolence (25%).Conclusions: Our study confirmed the efficacy and tolerability of adjunctive PER in Chinese patients in real-life conditions. Based on our treatment experience, a lower maintenance dose of PER would be needed in Chinese patients.

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Section: Discussioncontrasting

confidence: 94%

Efficacy and Tolerability of Perampanel as Adjunctive Therapy in Chinese Patients With Focal-Onset Seizures: An Observational, Prospective Study

et al. 2021

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“…The above statement is supported by results obtained in randomized double-blind trials [ 9 – 14 ] and observational studies [ 15 , 16 ]. In particular, in an open-label extension study that followed up patients with focal seizures, retention rates were found to be 46% at 3 years and 39% at 4 years [ 11 ], which are similar to those reported in studies that evaluated retention for other ASMs for 2 or more years [ 17 , 18 ].…”

Section: Resultsmentioning

confidence: 55%

“…Of note, the improvement in seizure control at a dose of 4 mg/day was greater in patients not receiving enzyme inducing ASMs, whereas the occurrence of adverse effects (AEs) at that dose was similar in patients on and off enzyme inducers [ 23 ]. Recent multicenter open-label prospective trials reported that use of PER as first add-on at a median dose of 6 mg/day was associated with improved control of focal seizures, with or without evolution to FBTCS, as well as GTCS [ 15 , 16 ].…”

Section: Resultsmentioning

confidence: 99%

“…A post-hoc analysis of data from Phase III studies has also suggested that tolerability is improved when PER is used as an early add-on treatment [ 22 ]. More recent prospective or retrospective studies have reported that, when PER is prescribed as first add-on, the frequency of AEs is halved, especially when low doses (≤ 6 mg) and a slow titration (2 mg/day every > 2 weeks) are used [ 15 , 16 ].…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2021

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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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“…The development and availability of perampanel as an add-on treatment in epilepsy with focal onset has led to widespread clinical use of this drug, mainly for resistant and refractory epilepsies [ 18 ]. Although early data reported side effects related to mood alteration and aggressive behavior [ 19 , 20 ], more data on good tolerability and efficacy have now been collected [ 21 , 22 ], thus improving the safety of perampanel use.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effect of Perampanel and Temozolomide in Human Glioma Cell Lines

Salmaggi

Corno

Maschio³

et al. 2021

JPM

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Glioblastoma is characterized by a high proliferative rate and drug resistance. The standard of care includes maximal safe surgery, followed by radiotherapy and temozolomide chemotherapy. The expression of glutamate receptors has been previously reported in human glioma cell lines. The aim of this study was to examine the cellular effects of perampanel, a broad-spectrum antiepileptic drug acting as an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) glutamate receptor antagonist, alone or in combination with temozolomide. Four human glioma cell lines were exposed to different concentrations of perampanel and temozolomide, alone or in combination. The type of drug interaction was assessed using the Chou-Talalay method. Apoptosis, cell cycle perturbation, and glutamate receptors (GluRs) subunit expression were assessed by flow cytometry. Perampanel significantly inhibited the growth, inducing high levels of apoptosis. A strong synergistic effect of the combination of perampanel with temozolomide was detected in U87 and A172, but not in U138. Treatment with perampanel resulted in an increased GluR2/3 subunit expression in U87 and U138. Perampanel displays a pro-apoptotic effect on human glioblastoma cell lines when used alone, possibly due to increased GluR2/3 expression. The observed synergistic effect of the combination of temozolomide with perampanel suggests further investigation on the impact of this combination on oncologic outcomes in glioblastoma.

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Efficacy and tolerability of perampanel as a first add-on therapy with different anti-seizure drugs

Cited by 39 publications

References 48 publications

Efficacy and Tolerability of Perampanel as Adjunctive Therapy in Chinese Patients With Focal-Onset Seizures: An Observational, Prospective Study

Efficacy and Tolerability of Perampanel as Adjunctive Therapy in Chinese Patients With Focal-Onset Seizures: An Observational, Prospective Study

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

Synergistic Effect of Perampanel and Temozolomide in Human Glioma Cell Lines

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