Safety Of Perampanel Research Articles

Effectiveness and safety of Perampanel in refractory status epilepticus: a case series.

Perampanel is a selective non-competitive antagonist of AMPA receptors, and the first agent of this class to become available for the treatment of epilepsy. It could be a useful tool for treatment of refractory status epilepticus (RSE). We describe a series of eight RSE cases treated with Perampanel. Perampanel was successful in terminating SE in all the described cases. Only in one patient a severe psychomotor agitation occurred, but without needing PER discontinuation. No other adverse events were observed. Our case series of eight patients, albeit small, broadens the clinical experiences on the efficacy and safety of PER as a treatment for RSE. It may also support the early use of PER, considering the role of AMPA receptors in sustaining epileptic firing in SE. Further studies are warranted to clarify the potential of Perampanel in the treatment of status epilepticus and, in particular, in RSE.

Efficacy of perampanel by etiology in Japanese patients with epilepsy-subpopulation analysis of a prospective post-marketing observational study.

To examine the efficacy and safety of perampanel (PER) in patients with post-stroke epilepsy (PSE), brain tumor-related epilepsy (BTRE), and post-traumatic epilepsy (PTE) using Japanese real-world data. The prospective post-marketing observational study included patients with focal seizures with or without focal to bilateral tonic-clonic seizures who received PER combination therapy. The observation period was 24 or 52 weeks after the initial PER administration. The safety and efficacy analysis included 3716 and 3272 patients, respectively. This post hoc analysis examined responder rate (50% reduction in seizure frequency), seizure-free rate (proportion of patients who achieved seizure-free), and safety in patients included in the post-marketing study who had PSE, BTRE, and PTE in the 4 weeks prior to the last observation. Overall, 402, 272, and 186 patients were included in the PSE, BTRE, and PTE subpopulations, and 2867 controls in the "Other" population (etiologies other than PSE, BTRE, or PTE). Mean modal dose (the most frequently administered dose) values at 52 weeks were 3.38, 3.36, 3.64, and 4.04 mg/day for PSE, BTRE, PTE, and "Other," respectively; PER retention rates were 56.2%, 54.0%, 52.6%, and 59.7%, respectively. Responder rates (% [95% confidence interval]) were 82% (76.3%-86.5%), 78% (70.8%-83.7%), 67% (56.8%-75.6%), and 50% (47.9%-52.7%) for PSE, BTRE, PTE, and "Other," respectively, and seizure-free rates were 71% (64.5%-76.5%), 62% (54.1%-69.0%), 50% (40.6%-60.4%), and 28% (25.8%-30.1%), respectively. Adverse drug reactions tended to occur less frequently in the PSE (14.7%), BTRE (16.5%), and PTE (16.7%) subpopulations than in the "Other" population (26.3%). In real-world clinical conditions, efficacy and tolerability for PER combination therapy were observed at low PER doses for the PSE, BTRE, and PTE subpopulations. To find out how well the medication perampanel works and whether it is safe for people who have epilepsy after having had a stroke, brain tumor, or head injury, we used information from real-life medical situations in Japan. We looked at the data of about 3700 Japanese patients with epilepsy who were treated with perampanel. We found that perampanel was used at lower doses and better at controlling seizures, and had fewer side effects for patients with epilepsy caused by these etiologies than the control group.

Perampanel as monotherapy or first adjunctive therapy in pediatric and adult patients with epilepsy: the first United States-based phase IV open-label ELEVATE study

ELEVATE (Study 410; NCT03288129) is the first prospective, multicenter, open-label, Phase IV study of perampanel as monotherapy or first adjunctive therapy in patients aged ≥ 4 years with focal-onset seizures or generalized tonic–clonic seizures in the United States. The study included Screening, Titration (≤ 13 weeks), Maintenance (39 weeks), and Follow-up (4 weeks) Periods. During Titration, perampanel was initiated at 2 mg/day and up-titrated to 4 mg/day at Week 3. Depending on response and tolerability, optional up-titrations to a maximum of 12 mg/day occurred. The primary endpoint was retention rate; additional endpoints included seizure-freedom rate, 50% responder rate, and incidence of treatment-emergent adverse events (TEAEs). At baseline, 10 (18.5%) patients were assigned to the monotherapy group and 44 (81.5%) patients to the first adjunctive therapy group. However, due to the addition of an anti-seizure medication along with perampanel on the first day of treatment, one patient was excluded from the monotherapy subgroup analyses. The mean perampanel exposure duration was 39.8 weeks and 32 (59.3%) patients completed the study. Retention rate at 12 months (or study completion) was 63.0% (monotherapy, 77.8%; first adjunctive therapy, 59.1%). Seizure-freedom rate during the Maintenance Period was 32.7% (monotherapy, 44.4%; first adjunctive therapy, 29.5%) and the 50% responder rate was 78.7% (monotherapy, 85.7%; first adjunctive therapy, 76.9%). TEAEs and serious TEAEs were reported by 88.9% (n = 48/54) and 7.4% (n = 4/54) of patients, respectively. Overall, the efficacy and safety of perampanel as monotherapy or first adjunctive therapy support the use of perampanel as early-line treatment for epilepsy.

Efficacy and safety of adjunctive perampanel treatment in pediatric patients with epilepsy aged 4-12years: a real-world study.

To determine the efficacy and safety of perampanel (PER) as an adjunctive therapy in children aged 4-12years with epilepsy. We performed a non-randomized, open-label, placebo-uncontrolled, real-world self-controlled study that included 216 young children (aged 4-12years) with epilepsy who received PER as adjunctive therapy at the children's hospital affiliated with Chongqing Medical University from July 4, 2020, to September 20, 2023. (1) The efficacy rates of adjunctive PER therapy at 3, 6, 9, and 12months were 62.8%, 67.8%, 65.3%, and 61.2%, respectively. PER showed efficacy in alleviating focal seizures, generalized tonic-clonic seizures, myoclonic seizures, and absence seizures. The efficacy rates for variants of self-limited epilepsy with centrotemporal spikes (SeLECTS) and Lennox-Gastaut syndrome (LGS) were 89.5% and 66.7%, respectively. (2) Focal non-motor onset seizures with or without impaired awareness, focal to bilateral tonic-clonic seizures (FBTCS), LGS, variants of SeLECTS, the number of concomitant antiseizure medications (ASMs), a family history of epilepsy, and focal lesions on cranial magnetic resonance imaging were independent factors affecting efficacy. The order of PER addition did not affect efficacy. The retention rates at 3, 6, 9, and 12months were 90.7%, 84.7%, 74.7%, 64.9%, respectively. (3) Adverse reactions occurred in 45 patients (45/216, 20.8%), with irritability/aggressive behavior (18/216, 8.3%) and somnolence (14/216, 6.5%) being the most common. Twelve patients (12/216, 5.6%) withdrew from the study because of adverse reactions. In young Chinese children with epilepsy, PER is effective, safe, and well-tolerated as an adjunctive therapy, making it a viable option for use with broad-spectrum ASMs.

Efficacy and safety of Perampanel in the treatment of post stroke epilepsy: A multicenter, real-world study

BackgroundSince 2019, Perampanel (PER) has been endorsed in China as an adjunctive treatment for focal seizures, both with and without impaired awareness, and for the transition from focal to bilateral tonic-clonic seizures. Limited research exists regarding the efficacy of PER in treating post-stroke epilepsy (PSE) in China. Empirical studies are essential to guide treatment protocols. We conducted a retrospective study to assess the efficacy and tolerability of PER in 58 PSE patients treated between October 2019 and July 2023. MethodThis study encompassed 58 patients with PSE, treated with PER either as monotherapy or as part of adjunctive therapy, and underwent follow-up for a minimum duration of 6 months. The study assessed changes in seizure frequency, adverse events (AEs), drug retention rate, maintenance dose, and adverse reactions following PER treatment. ResultsThe study included 58 PSE patients, with 60.3% males and 39.7% females, ranging in age from 18 to 89, mostly within the 61–70 age group. Ischemic strokes constituted 58.6% of cases, while hemorrhagic strokes accounted for 41.4%. Focal seizures, either with or without impaired awareness, were noted in 62.1% of patients, and a transition from focal to bilateral tonic-clonic seizures was seen in 32.8%. The retention rates for PER at 3 and 6 months stood at 94.8% and 84.5% respectively, and the most commonly administered maintenance dose was 4 mg/day (41.28%). In the adjunctive therapy group, efficacy rates were 66.7% at 3 months and 78.6% at 6 months, compared to 80.0% at 3 months and 85.7% at 6 months in the monotherapy group. In the efficacy analysis, with a criterion of ≥50% reduction in seizure frequency, the overall efficacy rates at 3 and 6 months were 69.1% and 79.6%, respectively. Adverse reactions occurred in 46.6% of patients, primarily involving irritability and somnolence (both 27.6%), with no marked difference in incidence between the adjunctive and monotherapy groups (P > 0.05). ConclusionPER exhibits favorable efficacy and tolerability in Chinese PSE patients, possibly at lower doses.

Long-term efficacy and safety of perampanel as an add-on therapy in patients with epilepsy

BackgroundPerampanel (PER) is a newly developed amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist that has been globally approved for the treatment of both focal and generalized seizures. The efficacy and safety of PER have only been reported over short periods of treatment so far. This study aims to clarify the long-term efficacy and safety of PER as an add-on therapy. MethodThis retrospective observational study investigated 176 epilepsy patients who received PER as add-on medical therapy in two Japanese epilepsy centers between June 2016 and July 2022. The adherence, seizure frequency, and plasma concentration of PER were evaluated at three time points: 6 months, 12 months, and 24 months or longer after the start of adjunctive PER treatment. Results112 patients undergoing PER treatment were evaluated at 6 months, 86 were evaluated at 12 months, and 52 were evaluated at 24 months or longer. Overall, 42.9 % (48/112), 45.4 % (40/86), and 44.2 % (23/52) of the patients were seizure-free at 6, 12, and 24 months or longer, respectively. The rate of PER tolerance was 78.3 %, 69.9 %, and 54.7 % at 6, 12, and 24 months or longer, respectively. At the latest timepoint, the seizure-free group was taking a significantly lower dose of PER than the seizure-remnant group, and the number of anti-seizure medications (ASMs) was associated with seizure outcomes. In addition, the seizure-free rate was significantly higher in patients who received PER as a first add-on than in those who received it as a late add-on. No significant difference was found in the plasma concentration of PER between the seizure-free and seizure-remnant groups at 24 months or longer. Among the patients receiving PER at dose of 2 mg, however, the plasma concentrations were significantly higher in the seizure-free group than in the seizure-remnant group (282.7 ± 109.8 μg/ml vs 94.7 ± 54.9 μg/ml, p = 0.0024). ConclusionThis long-term retrospective observational study provides evidence of the efficacy and safety of PER over 2 years treatment period in Japan. Notably, patients who started on PER as the first add-on showed a better seizure outcome than those who received it as a late add-on over the long term. Measured plasma concentrations may provide valuable guidance for the management of patients. Higher plasma concentration at low dose PER may suggest the better seizure control.

Efficacy and safety of perampanel as the first add-on therapy for children with epilepsy: A real-world multicenter prospective observational study

ObjectivePerampanel (PER) is a new anti-seizure medication (ASM) with a novel mechanism of action. This study aimed to determine the efficacy and safety of PER when added to monotherapy in children and adolescents (age, 4–18 years) with epilepsy. MethodA multicenter prospective observational study was performed on children and adolescents (age, 4–18 years) with epilepsy who did not respond to ASM monotherapy between July 2021 and October 2022. PER was used as the first add-on therapy for the enrolled patients. Seizure-free rate, response rate, inefficacy rate, and drug retention rate were the main observation indicators during the 6 months of treatment. The patients were grouped based on treatment efficacy, and factors affecting efficacy were statistically analyzed. Adverse reactions were also recorded. ResultsIn this study, 93 patients with epilepsy were enrolled; among them, 9 patients were lost to follow-up (attrition rate, 9.7 %), and 84 were included in the analysis. Five patients with unknown efficacy discontinued taking PER early due to intolerable adverse reactions, and 79 patients (48 males, 31 females; mean age, 11.0 ± 3.9 years) finally remained. Genetic epilepsy and structural epilepsy were found in 22 patients and 36 patients, respectively. The mean duration of epilepsy history at the time of PER initiation was 4.0 ± 3.8 years, and the mean maintenance dosage of add-on PER was 4.5 ± 1.8 mg/day (equivalent to 0.14 ± 0.07 mg/kg/day). Among the 79 patients, 28 patients were diagnosed with epilepsy syndrome, including 13 patients having self-limited epilepsy with centrotemporal spikes, among whom 9 patients were seizure-free after adding PER during the 6-month follow-up (seizure-free rate, 69.2 %). For these 79 patients, the seizure-free, response, and retention rates at the end of follow-up were 45.6 %, 74.7 %, and 82.1 %, respectively. Among the 84 patients included in the analyses, adverse reactions occurred in 20 patients, mainly dizziness (8 patients), somnolence (6 patients), and irritability (4 patients), and 4 patients developed two adverse reactions simultaneously. Univariate analyses revealed statistically significant differences in efficacy between groups with structural and non-structural epilepsy and between groups with different baseline concomitant ASMs, suggesting that these factors affected the efficacy of PER as the first add-on therapy. ConclusionThe overall response rate of PER as the first add-on therapy for children and adolescents with epilepsy who were followed up for 6 months was 74.7 %, indicating a relatively favorable safety and tolerability profile. The group of the baseline concomitant ASM administered and the etiological classification of epilepsy as either structural or non-structural were the factors influencing the efficacy of PER as the first add-on therapy.

Efficacy and safety of perampanel in a randomized, placebo-controlled trial with an open-label extension in patients with seizures associated with Lennox-Gastaut syndrome (LGS)

Efficacy and safety of perampanel in a randomized, placebo-controlled trial with an open-label extension in patients with seizures associated with Lennox-Gastaut syndrome (LGS)

Plasma Concentration, Efficacy, and Tolerability of Perampanel in Chinese Pediatric Patients with Epilepsy: Real-World Clinical Experience.

Information on the efficacy and plasma concentration of perampanel (PER) in Chinese pediatric patients with epilepsy is limited. Therefore, this real-world retrospective study aimed to assess the efficacy, tolerability, and plasma concentration of the maximum dose of PER for epilepsy treatment in Chinese pediatric patients. A total of 107 pediatric patients from 2 hospitals in China were enrolled in this study. The plasma concentration of PER was determined using ultrahigh-performance liquid chromatography. The primary efficacy endpoint was the seizure reduction rate after PER treatment at the last follow-up. The response rate to PER therapy was 59.8% (64/107). The authors observed that patients younger than 6 years of age (n = 49) showed a significantly lower concentration-to-dose ratio than patients with ages between 6 and 14 years (n = 58) (2.2 ± 1.7 vs. 3.0 ± 1.8 mcg·mL -1 ·kg·mg -1 , respectively; P < 0.05). Patients who received enzyme-inducing antiseizure medication had significantly lower concentration-to-dose ratios than those who did not receive enzyme-inducing antiseizure medication (EIASM) (2.1 ± 1.8 vs. 3.1 ± 2.0 mcg·mL -1 ·kg·mg -1 , P < 0.05). A total of 37 patients (34.6%) reported treatment adverse events. Patients with somnolence and irritability had a significantly higher PER plasma concentration than the "no treatment-emergent adverse effect" groups ( P < 0.05). PER is an effective and well-tolerated treatment option for patients with epilepsy. To ensure the clinical efficacy and safety of PER in pediatric patients, it is necessary to monitor its plasma concentrations.

Comparison of the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children and adolescents with newly diagnosed focal epilepsy.

Objective: This study aims to compare the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children with focal epilepsy (FE). Methods: This is an ambispective, single-center, non-inferiority study comparing the effectiveness and safety of perampanel (PER) monotherapy and oxcarbazepine (OXC) monotherapy in children with newly diagnosed FE. The primary endpoint was a six-month seizure freedom rate. The secondary endpoints included retention, responder, and seizure freedom rates at 3, 6, and 12 months, respectively. Adverse events (AEs) were also recorded for both groups. Results: One hundred and thirty children and adolescents aged from 4 to 18years newly diagnosed with FE between May 2020 and November 2022 in Wuhan Children's Hospital were included. There were 71 patients in the PER group and 59 patients in the OXC group. In the per protocol set (PPS), 50 (78.1%) in the PER group and 43 (78.2%) in the OXC group completed six months of treatment without seizures. The lower 95% CI (66.0%-87.5%) limit of PER was higher than the non-inferiority margin of 62.4% (80% of the 6-month seizure freedom rate in the OXC group); PER was non-inferior to OXC. The 3-month and 12-month seizure freedom rates were 77.1% and 82.9% for the PER group, respectively, while they were 80.4% and 75.8% for the OXC group. There were no serious adverse events in both groups. Conclusion: PER showed comparable effectiveness and safety compared with OXC in children with newly diagnosed focal epilepsy, which might be an effective and safe treatment for children and adolescents with newly diagnosed FE. Clinical Trial Registration: Identifier ChiCTR2300074696.

Efficacy and safety of perampanel as early add-on therapy in Chinese patients with focal-onset seizures: a multicenter, open-label, single-arm study.

No interventional study has been conducted in China to assess efficacy and safety of perampanel in treating Chinese patients with epilepsy, nor has there been any study on perampanel early add-on therapy in China. This interventional study aimed to assess efficacy and safety of perampanel as an early add-on treatment of focal-onset seizures (FOS) with or without focal-to-bilateral tonic-clonic seizures (FBTCS) in Chinese patients. In this multicenter, open-label, single-arm, phase 4 interventional study, Chinese patients ≥ 12 years old with FOS with or without FBTCS who failed anti-seizure medication (ASM) monotherapy from 15 hospitals in China were enrolled and treated with perampanel add-on therapy (8-week titration followed by 24-week maintenance). The primary endpoint was 50% responder rate. Secondary endpoints included seizure-freedom rate and changes in seizure frequency from baseline. Treatment-emergent adverse events (TEAEs) and drug-related TEAEs were recorded. The full analysis set included 150 patients. The mean maintenance perampanel dose was 5.9 ± 1.5 mg/day and the 8-month retention rate was 72%. The 50% responder rate and seizure-freedom rate for all patients during maintenance were 67.9 and 30.5%, respectively. Patients with FBTCS had higher 50% responder rate (96.0%) and seizure-freedom rate (76.0%) during maintenance. Patients on concomitant sodium valproate had a significantly higher seizure-freedom rate than those on concomitant oxcarbazepine. Eight-six (55.1%) patients experienced treatment-related TEAEs, and the most common TEAEs were dizziness (36.5%), hypersomnia (11.5%), headache (3.9%), somnolence (3.2%), and irritability (3.2%). Withdrawal due to TEAEs occurred to 14.7% of the patients. Perampanel early add-on was effective and safe in treating Chinese patients≥12 years old with FOS with or without FBTCS.Clinical trial registrationwww.chictr.org.cn, Identifier ChiCTR2000039510.

Perioperative perampanel administration for early seizure prophylaxis in brain tumor patients.

The efficacy of perioperative prophylactic antiepileptic drug therapy in "seizure-naïve" patients with brain tumor, including glioblastoma (GBM), remains controversial. This study investigated whether perampanel (PER) is effective and safe for preventing perioperative onset of epileptic seizures, so-called early seizure, in patients with brain tumors. Forty-five patients underwent tumor resection through craniotomy for a primary supratentorial brain tumor at Ehime University Hospital between April 2021 and July 2022. PER was administered from the 1st to the 6th day after surgery for seizure prophylaxis. Occurrence of early seizure, hematological toxicities, and various side effects were recorded on postoperative days 7 and 14. In addition, the clinical course of these patients was compared with 42 brain tumor patients under the same treatment protocol who received levetiracetam (LEV) for seizure prophylaxis between April 2017 and October 2018. In 45 patients with brain tumor, including GBM, who received PER administration, no early seizures were identified within 7 days postoperatively. No adverse drug reactions such as hematological toxicity, liver or kidney dysfunction, or exanthematous drug eruption were observed in any cases. As side effects, somnolence was reported in 14 patients (31.1%), vertigo in 3 patients (6.7%), and headache in 3 patients (6.7%). Although somnolence and vertigo were difficult to assess in the case of intraparenchymal tumors, particularly GBM, these side effects were not identified in patients with extraparenchymal tumors such as meningiomas, epidermoid cysts, and pituitary adenomas. In addition, no significant differences were identified compared to patients who received LEV. The efficacy and safety of PER in preventing early seizures among patients with brain tumors were retrospectively evaluated. Perioperative administration of PER to patients with brain tumors may reduce the risk of early seizures without incurring serious side effects, showing no significant differences compared to patients who received LEV.

Efficacy and Safety of Perampanel in Children with Drug-Resistant Focal-Onset Seizures: A Retrospective Review

Background: Epilepsy is one of the most common neurological disorders. Existing antiseizure medications (ASMs) are still unable to control seizures in one-third of these patients, making the discovery of antiseizure therapies with novel mechanisms of action a necessity. Aim of the Study: This study aimed to determine the safety and efficacy of perampanel (PER) as an adjuvant treatment for children with drug-resistant focal-onset seizures with or without focal to bilateral tonic-clonic seizures. Patients and methods: This is a single-center retrospective study of 38 epileptic pediatric patients, aged 2 to 14, at King Faisal Specialist Hospital and Research Center whose seizures were pharmaco-resistant to more than two antiseizure medications and followed for at least three months after PER adjuvant therapy initiation. Efficacy was assessed by the PER response rate at 3-, 6-, and 12-month follow-up evaluations, and side effects were also reported. Results: Multiple seizure types were reported. Myoclonic seizures were the predominant type of epilepsy in 17 children (44.7%). At 3 months, 6 months, and 12 months of follow-up, approximately 23.4%, 23.4%, and 18.4% of the patients were seizure-free at these time points, respectively. Adverse events were documented in 14 patients (35.7%) and led to the discontinuation of PER in 26.3%, 31.6%, and 36.8% of the studied group at the 3-, 6-, and 12-month follow-ups, respectively. The most common adverse events included dizziness or drowsiness, irritability, gait disturbance, and confusion; however, all were transient, and no serious adverse effects occurred. Conclusion: Our findings confirm the therapeutic efficacy of adjunctive PER in the treatment of drug-resistant epilepsy in children. As an adjunctive treatment for epilepsy, perampanel demonstrated sufficient effectiveness and tolerability.

The Efficacy and Cognitive Impact of Perampanel Monotherapy in Patients with Self-Limited Epilepsy with Centrotemporal Spikes: A Retrospective Analysis.

The third generation of antiepileptic medication (ASM) perampanel (PER), is mostly used as an add-on treatment for refractory epilepsy patients, and rarely used as a monotherapy. This study aims to observe the efficacy and assess the cognitive effects of PER monotherapy in patients with self-limited epilepsy with centrotemporal spikes (SeLECTS). Through screening, 86 patients who were first diagnosed with SeLECTS and treated with PER monotherapy were included in this study. All patients were followed up at least 12 months, and Evaluated the efficacy and safety of PER by observing the seizures of patients. At the same time, we used the P300 event-related potential (ERP) component and Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) to evaluate the cognitive changes in children before and after treatment with PER. Ten percent of the children experienced adverse effects, such as dizziness, gait instability, and irritability. The drug retention rate at the last follow-up was 98.83%. Further more, the P300 ERP component and WISC-IV tests were performed no significant difference before and 12 months after PER monotherapy in SeLECTS children. The third-generation of ASM PER monotherapy had a clear effect in children with SeLECTS. A small dose of PER can control seizures well and has no obvious effect on cognitive development.

Effects of low-dose titration on the tolerability and safety of perampanel

PurposeTo evaluate the effects of low-dose titration on the tolerability and safety of perampanel. MethodsWe retrospectively reviewed the records of 1065 patients who started perampanel therapy and compared the incidence of adverse events after standard titration (Group A: starting dose, 2 mg/day; titration speed, 2 mg/2 weeks or longer) and low-dose titration (Group B: starting dose, < 1 mg/day; titration speed, < 1 mg/2 weeks or longer). ResultsAdverse events were reported in 158 patients (14.8%) within the initial first 90 days of starting perampanel (mean concentration, 331 ng/mL). At 90 days, the cumulative incidence of adverse events was significantly higher in Group A than in Group B (24.5% vs. 16.3%, respectively; log-rank test p < 0.001). A Cox proportional hazards model also showed that low-dose titration decreased the incidence risk of adverse events (adjusted hazard ratio, 0.49; 95% confidence interval, 0.35–0.69). When the groups were stratified by use of enzyme-inducing antiseizure medications (inducers), Group A patients without inducers had a significantly higher cumulative incidence of adverse events than the other three subgroups (26.7%, p < 0.001). In patients taking 2 mg of perampanel, median concentrations in patients with or without inducers were 43 ng/mL and 204 ng/mL, respectively. ConclusionPerampanel is generally initiated at 2 mg, but serum perampanel concentrations show substantial interindividual variation. Our study suggests that care must be taken when setting the starting dose of perampanel. In particular, low-dose titration is recommended in patients not taking inducers.

Perampanel in adjunctive therapy of patients with brain tumor-related epilepsy: real-world data

Background. Brain tumor-related epilepsy (BTRE) is an important and insufficiently studied interdisciplinary problem. In a significant part of brain tumor patients, the disease onsets with epileptic seizures. The course of tumor-associated epilepsy is often pharmacoresistant and requires rational polytherapy. To date, there are no uniform recommendations on the choice of an antiepileptic drug (AED) for the initial therapy of BTRE.Objective: retrospective analysis of the efficacy/tolerability of adjunctive therapy with perampanel in relation to epileptic seizures in patients with epilepsy associated with glial brain tumors and metastases.Material and methods. The analysis included 51 patients with glial tumors and brain metastases who were prescribed perampanel as part of adjunctive therapy. Its effectiveness against focal seizures (FS) and bilateral tonic-clonic seizures (BTCS) was evaluated at follow-up periods of &gt;1≥3≥6 months. A decrease in the frequency of seizures by 50% or more (responders) or by 100% (seizure freedom) was analyzed. An analysis of the influence of intervening factors in a multifactorial model, an assessment of the effectiveness of perampanel as a whole and a stratified assessment of intervening factors were carried out. The frequency and profile of adverse events (AEs) were also evaluated, including their possible association with the use of other AED.Results. In the multifactorial model, independent predictors of the clinical effect were the onset of the disease in the form of FS at &gt;1≥3≥6 months follow-up. None of AEDs used in the first line of therapy demonstrated an impact on the clinical effect. There were no predictors of clinical effect in patients with BTCS during the entire follow-up period. Out of 51 patients, 48 (94.1%) were responders, and in 36 of them (70.6%) the seizure freedom was registered. Among patients with FS, the proportion of responders was 83.3–90.9% at different follow-up periods, including 31.2–50.0% who showed seizure freedom. Among patients with BTCS, 86.7–92.3% became responders, including 56.1–88.5% who achieved seizure freedom. AEs were noted in 7 (13.7%) patients, the most common was aggression – 4 patients (7.8%). There were no cases required reduction the dose or discontinuation the treatment with perampanel due to AEs. In most patients at &gt;1≥3≥6 months follow-up, the median was 6 mg/day.Conclusion. The study performed in real-world practice confirmed the high efficiency and safety of perampanel in the adjunctive therapy of epileptic seizures associated with glial brain tumors and metastases, which together with the low potential of drug interactions allow us recommend the drug to this contingent of patients.

Therapeutic drug monitoring of perampanel in children diagnosed with epilepsy: Focus on influencing factors on the plasma concentration-to-dose ratio.

This study aimed to investigate the efficacy and tolerability of perampanel (PER) therapy and to optimize a specific plasma reference range for PER in children. Another major aim was to evaluate the potential determinators of PER concentration. Concentrations obtained from 80 children were analyzed for routine therapeutic drug monitoring (TDM) between 2021 and 2022. We retrospectively reviewed the clinical data of these patients and assessed the efficacy at 3 months after treatment initiation. Trough concentration-to-dose ratio (C0 /Dose ratio) of PER was compared among patients on various potential influencing factors. A 3-month PER therapy produced a ≥50% reduction in seizure frequency in 58.8% of patients. Twelve patients reported at least one adverse effect (AE), mainly dizziness. The monitoring data showed that the median C0 was 325.5ng/mL. Under maintenance dosages, approximately 75% of the C0 values were 180.0-610.0ng/mL. The C0 /Dose ratio in patients aged 1 to <4 was significantly lower by twofold than in those aged 4 to ≤12 years (P= 0.001). Enzyme-inducing ASMs (EIASMs) decreased the C0 /Dose ratio of PER by 25.9% (P= 0.165). In addition, seizure frequency reduction in responders was achieved at a median PER C0 value of 357 ng/mL, which was similar to the value of 314 ng/mL found in nonresponders (P= 0.288). No significant difference was found in PER C0 values between patients with and without AEs (P= 0.082). In this study, PER treatment showed acceptable efficacy and tolerance in Chinese children with epilepsy. Contributing factors like age to variable C0 /Dose ratios were identified, and complex PER-ASMs interactions were observed. Notably, the reference range, that is, 180.0-610.0ng/mL, for routine PER monitoring may be more applicable for them. Routine TDM should be considered a positive attempt to manage the effectiveness and safety of PER.

Effectiveness and safety of perampanel as adjunctive therapy among Chinese patients with focal-onset epilepsy: A real-world prospective observational study

ObjectivePerampanel (PER) has previously been shown to be effective and tolerable when used as an adjunctive therapy for patients with focal-onset seizures (FOS). This study aimed to evaluate the effect of PER as adjunctive therapy for patients with FOS in the Chinese population under real-world conditions for 1 year. MethodsA prospective, single-center, 1-year observational study was conducted at Huashan Hospital, enrolling both under age (≥4 years old) and adult patients with FOS. Response to PER was assessed at 3-, 6-, and 12-month checkpoints by analyzing the 50 % responder rate, the seizure-free rate, and reduction in seizure frequency. ResultsOne hundred and eight patients (mean age: 26.6 years, 56.5 % males) with FOS were included, with seventy-six patients finishing the 1-year follow-up (retention rate: 70.4 %, mean PER dose: 4.3 mg/day). The seizure frequency was reduced significantly at 3, 6, and 12 months relative to baseline (p < 0.001 for each seizure type). At 12 months, the responder rate was 65.8 %, and the seizure-free rate was 39.5 %. A significantly higher responder rate was found in patients with focal to bilateral tonic–clonic seizures (p = 0.024), among which the percentage of patients with sleep-related epilepsy was significantly high (p = 0.045). Responders had a lower number of concomitant anti-seizure medications (ASMs) than the non-responders (p = 0.009). Drug-related adverse events (AEs) were reported in 37 % of patients, mostly mild or moderate, and the patients who experienced AEs had a higher daily dose of PER than those who did not (p = 0.026). ConclusionPerampanel, an add-on therapy for focal-onset seizures, was found to be effective and tolerable in Chinese patients at 12 months.

Safety evaluation of perampanel as monotherapy or first adjunctive therapy in patients with epilepsy

ABSTRACT Introduction There is a need for anti-seizure medications (ASMs) that are well tolerated and effective as monotherapy or first adjunctive therapy to reduce the need for adjunctive ASMs to treat newly diagnosed epilepsy, and to reduce the number of concomitant ASMs in patients with refractory epilepsy. Although the pivotal trials of perampanel evaluated its adjunctive use in patients with refractory seizures, open-label/real-world studies support its use in first/second-line settings. Areas covered This paper reviews the pharmacology, efficacy, and safety/tolerability of perampanel, focusing on its use as monotherapy or first adjunctive therapy. The safety of perampanel in special populations and its safety/tolerability compared with that of other ASMs is also discussed. Expert opinion Perampanel is a favorable candidate for initial or first adjunctive therapy due to its favorable efficacy and safety/tolerability as monotherapy and adjunctive therapy, its long half-life and ease of use, and its limited drug–drug interactions. The proposed mitigation strategies for managing the risk of serious psychiatric adverse events are appropriate patient selection, use of low doses, and slow titration. The growing body of evidence might shift current treatment strategies toward the early use of perampanel and its use at a low dose (4 mg/day).

Effectiveness of Perampanel as the Only Add-on: Retrospective, Multicenter, Observational Real Life Study on epilepsy patients.

Perampanel (PER) is indicated as adjunctive antiseizure medication (ASM) in adolescents and adults with epilepsy. Data from clinical trials show good efficacy and tolerability, while limited information is available on the routine clinical use of PER, especially when used as only add-on treatment. we performed an observational, retrospective, multicenter study on people with focal or generalized epilepsy aged >12 years, consecutively recruited from 52 Italian epilepsy centers. All patients received PER as the only add-on treatment to a background ASM according to standard clinical practice. Retention rate, seizure frequency and adverse events were recorded at 3, 6 and 12 months after PER introduction. Sub-analyses by early or late use of PER and by concomitant ASM were also conducted. 503 patients were included (age 36.5±19.9 years). Eighty-one per cent had focal epilepsy. Overall, the retention rate was very high in the whole group (89% at 12 months) according with efficacy measures. No major differences were observed in the sub-analyses, although patients who used PER as early add-on, as compared with late add-on, more often reached early seizure freedom at 3 months follow-up (66% vs. 53%, p=0.05). Treatment-emergent adverse events occurred in 25%, far less commonly than in PER randomized trials. this study confirms the good efficacy and safety of PER for focal or generalized epilepsy in real-life conditions. We provide robust data about its effectiveness as only add-on treatment even in patients with a long-standing history of epilepsy and previously treated with many ASMs.