Safety Of Perampanel Research Articles

Efficacy, tolerability and safety of perampanel in population with pharmacoresistant focal seizures: A systematic review and meta-analysis

BackgroundFocal seizures are associated with various co-morbidities. Seizure disorders also affect the quality of life of the patients. A huge proportion of patients continue to have uncontrolled seizures despite the availability of numerous antiepileptic drugs. Novel therapeutic targets too, have failed to overcome this problem. Therefore, drugs acting on conventional targets are being explored. Perampanel is one such drug. The present study aimed to assess its efficacy, safety, and effect on quality of life and cognition in patients aged 12 years and above. MethodsDatabase search was conducted using keywords perampanel, partial seizures and randomized controlled trials (RCTs). Single and double blinded RCTs were included in the analysis. The primary outcomes assessed were 50% responder rate and seizure freedom rates. Secondary outcomes assessed were Improvement in Clinical Global Improvement for Change (CGI-C), number of patients who experienced adverse events, number of patients who withdrew from trials, adverse drug reaction (ADR) profile from Vigibase, long term safety, quality of Life (QoL) assessment and cognitive assessment, especially in adolescents. The Risk ratios (RR) were calculated for these parameters. Results24 full text articles were obtained out of a total 421 studies. From these seven double blind randomized controlled trials were included in the meta-analysis. Perampanel treated patients showed higher 50% responder rates than those treated with placebo. The Risk Ratios (RRs) were 1.39 [95% confidence interval (CI) 1.08–1.79], 1.83 [95% CI 1.51 – 2.22] and 1.81 [95% CI 1.45–2.27] for the 4 mg per day, 8 mg once daily and 12 mg once daily subgroups of perampanel respectively. The RRs for the seizure freedom rates were 4.52 [95% CI 1.30–15.73], 3.65 [95% CI 1.40–9.52] and 2.14 [95% CI 1.11–4.11] for 4 mg per day, 8 mg once daily and 12 mg once daily subgroups of perampanel respectively. There was a significantly higher risk of TEAEs with the 8 mg and 12 mg doses of perampanel as compared to that with placebo. Number of patients who withdrew from the trials due to adverse events was statistically significant in only the 12 mg subgroup of perampanel in comparison to that with placebo group. ConclusionPerampanel was observed to be an effective add on drug for treating pharmacoresistant focal seizures. The patients achieved higher 50% response rates and freedom from seizures with its use. Tolerability of perampanel was more at lower doses.

Perampanel for amyotrophic lateral sclerosis: A systematic review and meta-analysis.

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease. There is still no established cost-effective treatment that can improve functional status and survival of ALS patients. Perampanel, by inhibiting neuronal calcium ion influx and preventing dyslocalization of nuclear proteins, has the potential to ameliorate ALS neurodegeneration. This study aims to determine the efficacy and safety of perampanel among ALS patients in terms of improvement in functional status using a review of relevant studies. MedLine, Cochrane Central Register for Controlled Trials, Scopus, Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde, ClinicalTrials.gov website, and HERDIN databases were searched from inception to August 2021 for relevant studies. The search yielded 132 articles; 3 studies were included in the analysis. Pooled evidence shows that perampanel compared to placebo significantly improves cortical motor hyperexcitability but not the ALS functional rating scale-revised score. Perampanel is associated with adverse events such as aggression, somnolence, anger, and dysarthria. There is no sufficient evidence to support the role of perampanel in improving functional status of ALS patients. Although it can ameliorate motor cortical hyperexcitability, its clinical benefit has not yet been elucidated. Perampanel is not well tolerated among ALS patients as it is associated with adverse events such as aggression, somnolence, anger, and dysarthria. Further studies investigating the role of perampanel early in the ALS disease course, excluding ALS patients with frontotemporal lobe degeneration features and C9ORF72 repeat expansion, and using gradual drug titration schedule are needed to evaluate the potential benefit of perampanel in ALS.

Effectiveness and safety of perampanel in Chinese paediatric patients (2-14 years) with refractory epilepsy: a retrospective, observational study.

We report our clinical experience of the effectiveness and tolerability of adjunctive perampanel treatment in a Chinese paediatric population with refractory epilepsy. We also compare the effectiveness and tolerability of perampanel with or without concomitant oxcarbazepine or levetiracetam. This retrospective observational study was conducted from September 2019 to September 2020 in the paediatric neurology clinics of two tertiary hospitals in the Chinese mainland. We reviewed the data obtained from 96 paediatric patients aged 2-14 years whose seizures were pharmacoresistant and who could be followed up for a minimum of six months. The effectiveness was estimated by the perampanel response rate at 6- and 12-month follow-up evaluations. Adverse events were also recorded. Patients were stratified by age (2-7 and 7-14 years), and with/without concomitant oxcarbazepine or levetiracetam. The population comprised 96 patients with refractory epilepsy. The retention rate was 84.4% and 81.0% at 6 and 12 months, respectively. The most common dose used was 4mg (48.5%). Corresponding 50% responder and seizure freedom rates were as follows: 46.9% and 20.8% at six months, and 51.2% and 27.4% at 12 months, respectively. Adverse effects were reported in 22 patients (22.9%). The most common adverse effects were irritability, somnolence, and dizziness. The 50% and 100% responder rates and adverse effects were greater in patients aged 7-14 years than in those aged 2-7 years. The proportion of responder and seizure-free rates and adverse effects were similar with or without oxcarbazepine. Perampanel was more effective in patients concomitantly treated with levetiracetam, however, this did not result in significantly more adverse events, including aggression. The present study suggests that perampanel, with or without concomitant oxcarbazepine or levetiracetam, is generally safe, well-tolerated, and efficacious in paediatric patients with uncontrolled epilepsy in a clinical setting.

Long-term efficacy and safety of perampanel as a first add-on therapy in patients with focal epilepsy: Three-year extension study

PurposeWe investigated the long-term efficacy and safety of perampanel as a first add-on therapy in patients with focal epilepsy. MethodsThis retrospective study represented the 3-year extension phase of a multicenter, open-label, phase 4, prospective study of perampanel as a first add-on therapy in patients with focal epilepsy. Seizure and safety outcomes were assessed annually from the start of the extension study, and the retention rate was calculated from the start of perampanel exposure in the original study. ResultsThe 50% responder and seizure freedom rates were 84.8% and 58.7%, respectively, during the third year and 71.7% and 32.6%, respectively, during the entire 3-year period of the extension study. The 1-, 2-, and 3-year retention rates were 62.5%, 53.1%, and 52.1%, respectively. Efficacies were higher in patients that were aged >55 years, male, and receiving ≤4 mg of perampanel. Perampanel was generally well tolerated; 47.3% of patients experienced at least one adverse event during the 3 years of extension (46 adverse events (AEs) in 35 patients). The most common AEs were dizziness (33.8%), somnolence (5.4%), anger (4.1%), and irritability (4.1%). AEs were resolved with perampanel dose reduction or discontinuation in 10 (13.5%) and 12 (16.2%) patients, respectively. ConclusionLong-term treatment with perampanel as a first add-on therapy did not raise new safety signals in patients with focal epilepsy. Especially at low perampanel doses (≤4 mg/day), sustained improvement in seizure control was achieved, which could potentially avoid adverse drug reactions.

Randomized phase 2 study of perampanel for sporadic amyotrophic lateral sclerosis

ObjectiveTo evaluate the efficacy and safety of perampanel in patients with sporadic amyotrophic lateral sclerosis (SALS).MethodsThis randomized, double-blind, placebo-controlled, multicenter, phase 2 clinical study was conducted at 12 sites. Patients with probable or definite ALS as defined by revised El Escorial criteria were enrolled. Sixty-six patients were randomly assigned (1:1:1) to receive placebo, 4 mg perampanel, or 8 mg perampanel daily for 48 weeks. Adverse events (AEs) were recorded throughout the trial period. The primary efficacy outcome was the change in Amyotrophic Lateral Sclerosis Rating Scale-Revised (ALSFRS-R) score after 48 weeks of treatment.ResultsOne patient withdrew before starting the treatment. Of 65 patients included, 18 of 22 patients randomized to placebo (82%), 14 of 22 patients randomized to 4 mg perampanel (64%), and 7 of 21 patients randomized to 8 mg perampanel (33%) completed the trial. There was a significant difference in the change of ALSFRS-R scores [− 8.4 (95% CI − 13.9 to − 2.9); p = 0.015] between the placebo and the perampanel 8 mg group, primarily due to worsening of the bulbar subscore in the perampanel 8 mg group. Serious AEs were more frequent in the perampanel 8 mg group than in the placebo group (p = 0.0483).ConclusionsPerampanel was associated with a significant decline in ALSFRS-R score and was linked to worsening of the bulbar subscore in the 8 mg group.

An Open-Label Phase 2a Study to Evaluate the Safety and Tolerability of Perampanel in Cervical Dystonia.

Cervical dystonia (CD) is the most common focal isolated dystonia. Preclinical studies report that AMPA-selective glutamate receptor antagonists improve dystonia. Perampanel is a clinically available, AMPA receptor antagonist that has shown efficacy and safety in epilepsy. To determine safety and tolerability of perampanel in CD. We performed a phase 2a, open-label, multicenter study to evaluate tolerability and safety of perampanel in CD. Included subjects had primary CD; those on botulinum toxin were 8 weeks post last injection. All subjects received perampanel 2 mg/day, titrated 2 mg weekly over 6 weeks, to maximum 12 mg/day; maintenance phase was 4 weeks, ending at week 10. Primary endpoints included tolerability, defined as ability to remain on perampanel for the maintenance period, at any dose level and safety, determined from adverse events (AEs) collected at each visit. Secondary exploratory endpoints included Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), quality of life (cervical dystonia impact profile [CIDP]-58) and Clinical Global Impression of change (CGI). CD participants (n=25) were recruited. Eight subjects withdrew; 4 because of AEs, 3 for other reasons and 1 lost to follow up. One subject tolerated 12 mg/day. Eight subjects (30.8%) tolerated 2 mg, whereas 19.2% tolerated 4 mg/day, and 15.4% tolerated 6 mg or 8 mg/day. All subjects experienced AEs. The most common AEs were dizziness, imbalance, and irritability. Exploratory endpoints of TWSTRS showed some improved pain scores and CIDP-58 improved sleep. Tolerability to perampanel was variable in CD subjects. Lower doses would be considered for future studies in this population.

Efficacy and safety of perampanel in refractory and super-refractory status epilepticus: cohort study of 81 patients and literature review.

The effective dose of perampanel in status epilepticus (SE), refractory SE (RSE), and super-refractory SE (SRSE) in humans is unknown, and the potential of perampanel in treating SE has not been evaluated in a large cohort. Data of intensive care patients with RSE and SRSE treated with perampanel were retrospectively reviewed and analyzed. Eighty-one patients received perampanel, including 39 females with median age 64 [17-91] years, perampanel responders (n = 27), and non-responders (n = 54). The initial perampanel dose was positively associated with treatment response in patients with RSE or SRSE (OR = 1.27, 95% CI 1.03-1.57, p = 0.025), while the maximum dose was negatively associated with treatment response (OR = 0.74, 95% CI 0.58-0.96, p = 0.022). Hypoxia caused seizures in six patients; five died in hospital and one had severe disability. A statistically non-significant tendency toward better response was found in patients with unique SE type and cause, particularly in nonconvulsive status epilepticus (NCSE) without coma (NCSE without coma vs. generalized tonic-clonic seizure: OR = 4.14, 95% CI 0.98-17.47, p = 0.053). In the high-dose (≥ 16mg/day) groups, although distributions of modified Rankin Scale (mRS) scores were similar between perampanel responders and non-responders at discharge, a greater proportion of perampanel responders had less change in mRS scores from baseline than did perampanel non-responders (median mRS: 0 vs 4, p = 0.064). No cardiorespiratory adverse events or laboratory abnormalities were noted with perampanel treatment. Perampanel is effective and has a satisfactory safety profile in the emergency treatment of established RSE and SRSE.

Utility and Safety of Perampanel in Pediatric FIRES and Other Drug-Resistant Epilepsies.

Perampanel is a novel antiepileptic drug, which antagonises AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) glutamate receptor. We describe perampanel as an adjunctive treatment for FIRES (febrile infection-related epilepsy syndrome) and other drug-resistant epilepsies. A single-centre, observational, retrospective study involving 20 pediatric patients was conducted. Perampanel was started for three patients with FIRES, achieving seizure cessation in two patients within a day and on days 19 and 32 of illness. Doses used ranged from 4 to 12 mg/day, without any adverse effects reported or discontinuation of therapy. Responder-rate for other drug-resistant epilepsies is 25%. Median time to achieve ≥50% seizure reduction was 80 days (range: 26-326 days). Adverse effect reported in 47% of the patients includes central nervous system-related, and thrombocytopenia. Eight patients discontinued perampanel, because of ineffectiveness or adverse effects. The median time on perampanel before discontinuation was 179 days (range: 94-345 days). Perampanel may be of benefit in pediatrics FIRES and is of utility in other drug-resistant epilepsies.

Results of the Expert Forum on the application of perampanel in routine clinical practice

In February 2020, in Moscow, Expert Forum was held on the issues of the application of perampanel in routine clinical practice. The main aim of the Forum was to discuss the tolerance and safety profile of perampanel in patients with epilepsy in different age and gender groups in the conditions of routine clinical practice. Leading experts in neurology and epileptology took part in the Forum, wherein the acute data on the efficiency and safety of perampanel and the management of potential risks were presented.

Perampanel Confirms to Be Effective and Well-Tolerated as an Add-On Treatment in Patients With Brain Tumor-Related Epilepsy (PERADET Study)

Background: Epilepsy is one of the most common symptoms of brain tumors. It is often drug resistant and generally worsen patients' quality of life (QoL). Brain tumors release glutamate among other mediators, contributing to seizures onset, and this is accompanied by an increased AMPA receptors' expression on neuronal cells' membrane. Perampanel (PER) is a relatively new antiseizure medication (ASM) that acts as a selective non-competitive AMPA receptors' antagonist. Given its mechanism of action, we aimed to evaluate through a prospective, observational study, the efficacy and safety of PER as an add-on treatment in patients with brain tumor-related epilepsy (BTRE). The study was called PERADET.Methods: Thirty-six adult patients (intention to treat population-ITT) affected by BTRE, with uncontrolled focal-onset seizures treated with 1–3 ASMs were recruited from four Italian epilepsy centers. Perampanel was added-on, titrated from 2 mg/day up to a maximum of 12 mg/day. Tumor history and therapy, type, and seizures frequency, previous ASMs were collected at 6 and 12 months. A battery of QoL tests were administered at baseline, 6 and 12 months. The primary endpoint was to assess the efficacy of PER by calculating the percent change in seizure frequency and the responder rate. The secondary endpoints were tolerability, retention rate at 12 months, and improvement in quality of life.Results: At the end of 12 months, 21 patients (per protocol population-PP) were available for evaluation. In this population the responder rate (percentage of patients who experienced a 50% or greater reduction in seizure frequency) was 90.4 with 33.3% of patients being seizure-free. In the ITT group the responder rate at the end of 12 months was 66.6 with 25% of patients being seizure free. PER was well tolerated (30.6% of patients experienced an adverse event, none was severe; three needed a treatment interruptions).Conclusions: Our study indicate that PER may be efficacious against BTRE as suggested by its mechanism of action and our current knowledge on mechanisms of brain tumor epileptogenicity.Trial Registration Number (TRN): (Prot. n° 0008872.25-06-2019); RS 919/17.

A Study to Investigate Dosage, Effectiveness, and Safety of Perampanel When Used as First Add-on Therapy in Participants >=12 Years With Partial Onset Seizures With or Without Secondary Generalization or With Primary Generalized Tonic-Clonic Seizures Associated With Idiopathic Generalized Epilepsy

A Study to Investigate Dosage, Effectiveness, and Safety of Perampanel When Used as First Add-on Therapy in Participants >=12 Years With Partial Onset Seizures With or Without Secondary Generalization or With Primary Generalized Tonic-Clonic Seizures Associated With Idiopathic Generalized Epilepsy

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)

ObjectivePerampanel (PER) has been shown to be effective as an adjunctive therapy for controlling refractory focal-onset seizures (FOS). However, the information as early add-on for the treatment of FOS in the clinical practice is still scarce and must be further assessed. MethodsAn observational prospective study was conducted to evaluate the effectiveness of early add-on PER, assessed as 50% responders (seizure frequency reduced by at least 50% during the last 3 months as compared with baseline) rate at 6 and 12 months, in patients with FOS in the routine clinical practice of Spain. ResultsOne hundred and thirteen patients (mean age: 40.3 years, 51.3% male) with FOS received PER as early add-on (1st add-on: 37.2% and 2nd: 62.8%) for a mean exposure of 11 months (mean PER dose: 6.3 mg/day at month 12). At 6 months, 50.4% and 20.4% of the patients were responders and seizure-free (respectively) relative to baseline (3 months prior to PER initiation), and at 12 months, 68.1% and 26.5% of the patients were responders and seizure-free (respectively), relative to baseline (3 months prior to PER initiation). The retention rate at 6 and 12 months was 83.2% and 80.5%, respectively. The percentage of seizure-free patients at 12 months was significantly (p = 0.033) higher when PER was added as first vs. second add-on. The number of concomitant antiepileptic drugs (AEDs) was significantly reduced from baseline to 6 and 12 months (p = 0.001). Treatment was simplified in 23.9% of patients at the end of the observation period. Drug-related adverse events (AEs), most mild or moderate, were reported in 30.1% of patients, with irritability (8%) and dizziness (7.1%) as the most frequent ones. ConclusionsThis is the first observational, prospective study to evaluate efficacy and safety of early adjunctive treatment with PER in patients with focal epilepsy at 12 months. Perampanel demonstrated a good efficacy and safety profile when used at a median dose of 6 mg/day, regardless of the combination with other AEDs. Adverse events were mild or moderate, with dizziness being the most frequent one.

Effectiveness and safety of perampanel in adults with mesial temporal epilepsy: A single-center postmarketing study in Taiwan.

Mesial temporal lobe epilepsy (MTLE) is a common epilepsy syndrome often refractory to antiepileptic drug (AED) treatment. The purpose of this study was to evaluate the effectiveness and tolerability of perampanel (PER) as add-on treatment for patients of MTLE.We pooled retrospective data from adult patients with MTLE, from a tertiary center in Taiwan, who were prescribed PER between March 2016 and December 2016. The retention, responder, and seizure-free rate as well as the treatment emergent adverse events were assessed after 6 months of PER adjunctive treatment in this single-center postmarketing study.Review of medical records revealed that adequate data were available for 44 patients who were being administered PER (mean age: 42.0 ± 13.3 years, 24 females; baseline mean seizure frequency: 5.4 per 28 days). Twelve patients exhibited hippocampal sclerosis (HS). Open-label PER was added to ongoing medications. Twelve patients withdrew because of ineffectiveness (n = 6) or adverse effects (n = 6). The retention rate was 72.7% at 6 months. On final evaluation, with a mean PER dose of 5.7 mg/day for 6 months, a ≥50% reduction in seizure frequency was observed in 46.9% of the patients, and 5 patients became seizure-free. The effectiveness was similar for patients with or without HS. Twenty-three patients (52.3%) experienced adverse effects. The most common adverse effects were dizziness, ataxia, and irritability.Our results suggest that PER, at doses of 2 to 12 mg/day, reduces seizure frequency effectively with acceptable safety profiles for adults with MTLE.

A Study to Evaluate Efficacy and Safety of Perampanel Administered as an Adjunctive Therapy in Pediatric Participants With Childhood Epilepsy

A Study to Evaluate Efficacy and Safety of Perampanel Administered as an Adjunctive Therapy in Pediatric Participants With Childhood Epilepsy

Pharmacokinetic and pharmacodynamic considerations for the clinical efficacy of perampanel in focal onset seizures

ABSTRACTIntroduction: Medical therapy is the mainstay of management of epilepsy. Despite the increasing number of available antiepileptic drugs (AEDs), approximately one-third of epileptic patients do not have adequate control of seizures. There is still a need for the development of new AEDs with enhanced effectiveness and tolerability.Areas covered: The present manuscript is based on an Internet and PubMed search (January 2005 to August 2018). It is focused on pharmacokinetic and clinical data of perampanel (PER) for the treatment of epilepsy.Expert opinion: PER has a novel mechanism of action, which opens up new options for a rational combination therapy. Phase III trials have demonstrated the efficacy and safety of PER as adjunctive therapy for the treatment of partial-onset seizures (POS) and primary generalized tonic–clonic seizures in patients aged ≥12 years. PER is also approved by FDA as monotherapy for the treatment of POS. A clinical trial is ongoing to verify the efficacy and safety of PER monotherapy in untreated patients with POS. In the future, head-to-head comparisons are needed to determine the exact position of PER relative to other AEDs. Moreover, further studies are needed to evaluate the efficacy and safety of PER in patients aged <12 years.Abbreviations: 4βOHC: 4β-hydroxycholesterol; AUC: area under the curve; CBZ: Carbamazepine; CLCr: creatinine clearance; Cmax: maximum plasma concentration; CYP: cytochrome P; EIAED: enzyme-inducing antiepileptic drug; EMA: European Medicines Agency; FDA: Food and Drug Administration; GI: gastrointestinal; OXC: oxcarbazepine; PER: perampanel; PGTC: primary generalized tonic-clonic; PHT: phenytoin; POS: partial-onset seizures; QD: once-daily; TEAE: treatment-emergent adverse event; Tmax: median time to reach peak concentration; UGT: uridine diphosphoglucose-glucuronosyltransferase; VPA: valproic acid

Efficacy and tolerability of perampanel in children and adolescents with pharmacoresistant epilepsy: The first real-world evaluation in Asian pediatric neurology clinics

AimThis study investigated the efficacy and safety of perampanel (PER) adjunctive therapy in pediatric patients with epilepsy whose seizures are pharmacoresistant to existing antiepileptic drugs. MethodsA clinical retrospective study was conducted from 2016 to 2017 in the pediatric neurology clinic at a tertiary children's hospital. We reviewed the data obtained from 66 children whose seizures were pharmacoresistant to more than two antiepileptic drugs, and could be followed up for a minimum of 3 months after PER adjunctive therapy initiation. The efficacy was estimated by the PER response rate at 3-, 6-, and 12-month follow-up evaluations, and adverse events were also recorded. ResultsThe rate of seizure reduction of >50% was 30.3%, 37.5%, and 34.7% for all seizure types at 3, 6, and 12 months, in which 7.6%, 8.9%, and 14.3% of the patients became seizure-free at these time points, respectively. No significant differences were found between enzyme-inducing and nonenzyme-inducing antiepileptic drugs in combination with PER with regard to the responder rate. Five patients with Dravet syndrome were included in the study. Four of them (80%) exhibited 50% seizure reduction at the last visit, at which point, two patients (40.0%) were seizure-free. The retention rate was 51% at 12 months. Adverse events were documented in 25 patients (35.7%) and led to PER discontinuation in eight patients (12.1%). The most common adverse events comprised irritability, skin rash, dizziness, and somnolence; however, all were transient and successfully managed after PER dose reduction or discontinuation. ConclusionThe current data support the value of adjunctive PER in child and adolescent patients with pharmacoresistant epilepsy in daily clinical practice. Perampanel was efficacious and generally well-tolerated as an add-on treatment for epilepsy.

Perampanel, an AMPA receptor antagonist: From clinical research to practice in clinical settings.

Epileptic seizures are refractory to treatment in approximately one-third of patients despite the recent introduction of many newer antiepileptic drugs (AEDs). Development of novel AEDs therefore remains a high priority. Perampanel is a first-in-class non-competitive selective AMPA receptor antagonist with a unique mechanism of action. Clinical efficacy and safety of perampanel as adjunctive treatment for focal seizures with/without secondary generalization (±SG) and primary generalized tonic-clonic (PGTC) seizures have been established in five phase 3 randomized controlled trials (RCTs), and a long-term extension study, and perampanel is approved as monotherapy for focal seizures ±SG in the USA. In patients with focal seizures ±SG, add-on perampanel resulted in median percent reduction in seizure frequency 23.3%-34.5% and ≥50% responder rate 28.5%-37.6%; in PGTC seizures, these results were 76.5% and 64.2%, respectively. Efficacy among adolescents (reduction in seizure frequency 34.8%-35.6%; ≥50% responder rate 40.9%-45.0%) and elderly people (reduction in seizure frequency 12.5%-16.9%; ≥50% responder rate 22.2%-42.9%) is similar to those in adults, and results remain comparable between Asian (reduction in seizure frequency 17.3%-38.0%) and global populations. Perampanel has been extensively studied in real-world clinical practice, with similar efficacy and safety results to the RCTs (≥50% responder rate 12.8%-75.0%; adverse events of somnolence/sedation, dizziness, ataxia, and behavioral changes). Real-world observational studies suggest that perampanel tolerability can be improved by slow titration (2mg every 2-4weeks), and bedtime administration can mitigate somnolence and dizziness. Counseling about the potential for behavioral changes and close monitoring are recommended.

Preliminary Asian experience of using perampanel in clinical practice

BackgroundTo analyze the efficacy and safety of perampanel over a 3-month period in a sample of Asian people with epilepsy. MethodsThe efficacy and safety of perampanel as an adjunctive therapy for patients with epilepsy were retrospectively reviewed and analyzed. Patients were categorized according to seizure type, concomitant antiepileptic drug usage, and perampanel dosage. ResultsA total of 210 patients were included in the study and 131 patients completed 3 months of perampanel treatment. The average dosage of perampanel was 5.31 mg/day, and the 50% responder rate (≥50% seizure frequency reduction) in all patients was 45.8%, with a 27.5% seizure-free rate. For focal seizures, focal to bilateral tonic-clonic seizures, and primary generalized seizures, the 50% responder rates were respectively 29.4%, 49.5%, and 36.4%. In total, 39.5% of patients experienced adverse events within 3 months of observation period, and the rate of drug withdrawal due to adverse events was 8.6%. Dizziness, ataxia, irritability/aggression were the most common adverse events. ConclusionsThe efficacy and safety of perampanel in a real-world setting with Asian patients is comparable to that in clinical trials that have included fewer Asian patients.

Efficacy and safety of perampanel in Parkinson's disease. A systematic review with meta-analysis.

L-Dopa represents the mainstay of therapy of Parkinson's disease (PD), but its effectiveness is reduced with continued treatment and disease progression. Accordingly, there remains a need to explore novel treatment strategies to manage the signs and symptoms of the later disease stages. The aim of the study was to evaluate the efficacy and safety of adjunctive perampanel (PER) in patients with PD through a meta-analysis of existing trials. Randomized, placebo-controlled, double- or single-blind, add-on studies of PER in patients with PD were identified through a systematic literature search. The following outcomes were assessed: changes from baseline to final efficacy visit in total daily OFF time, activities of daily living during OFF time and motor function during ON time, incidence of adverse events (AEs), and treatment withdrawal. Four trials were included involving 2266 participants, 1449 and 817 for PER and placebo treatment groups, respectively. Four PER daily doses were tested, namely 0.5, 1, 2 and 4mg. There were no significant differences in any efficacy outcome between PER and placebo treated patients. The risk ratios (RRs) for AEs, severe AEs and treatment withdrawal were similar between placebo and PER at 0.5, 1 and 2mg; the 4mg daily dose was associated with an increased risk of AEs [RR 1.118 (1.047-1.193)], and withdrawal for AEs [RR 1.345 (1.034-1.749)] and for any reason [RR 1.197 (1.020-1.406)]. In PD patients experiencing motor fluctuations, adjunctive PER did not improve the motor state and was well-tolerated at the lower doses.

Short-term efficacy and safety of perampanel in patients with drug resistant epilepsy

Short-term efficacy and safety of perampanel in patients with drug resistant epilepsy