Optimal Use of Perampanel in Elderly Asian Patients with Epilepsy: Expert Opinion

Perampanel belongs to a novel class of antiseizure medications (ASMs). Studies examining the effect of hemodialysis on perampanel serum levels in clinical settings are lacking. We aimed to evaluate the changes in serum perampanel levels during hemodialysis. We studied patients with seizures who received oral perampanel between April 2020 and March 2023 and whose serum concentration of perampanel was measured before and after hemodialysis. We analyzed the serum concentrations of levetiracetam and lacosamide for comparison. Fourteen patients, with a mean age of 76.1 ± 7.88 years, were included. The dose of perampanel was 2.14 ± 1.27 mg. The hemodialysis clearance rate of perampanel, levetiracetam, and lacosamide was 0 ± 13%, 69 ± 11%, and 59.6 ± 8.2%, respectively. The post‐dialysis CD ratio decreased significantly with levetiracetam but not with perampanel. Adverse but acceptable effects of perampanel were observed in two patients. The serum concentrations of several ASMs have been shown to be reduced during hemodialysis. Our study revealed that the serum perampanel concentration does not decrease during hemodialysis. Owing to the low rate of adverse effects and the stability of perampanel serum concentration during hemodialysis, perampanel could be a favorable choice as an ASM for patients with seizures undergoing hemodialysis.Plain Language summaryOur study looked at how hemodialysis affects the serum levels of perampanel, a new type of medication for seizures. In 14 patients who started treatment between April 2020 and March 2023, perampanel serum levels did not decrease during hemodialysis, unlike other seizure medications. This shows that perampanel can be a good option for patients with seizures who need hemodialysis, with fewer side effects compared to other medications.

Section: Discussionmentioning

confidence: 52%

Serum perampanel levels in patients with seizures are not affected by hemodialysis

Nakazawa,

Shiraishi,

Matsuyoshi

et al. 2024

“…This trend of better seizure control in elderly Asians with perampanel has also been observed by epilepsy experts across Asia such that an expert opinion article was published in 2022. 23 Regarding tolerability, mean retention time in WRAPPER was 44.5 weeks (SD 1.7, 95% CI 41.2-47.8) comparable to that of PERMIT at 43.2 weeks (95% CI 42.4-43.6). Seizure exacerbation was the most common adverse effect at 35.7% (25/70) at 16 weeks.…”

Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

WRAPPER study: Real‐world effectiveness and tolerability of adjunctive perampanel for people with drug–resistant epilepsy in Hong Kong

Chan,

Leung

2023

ObjectiveThe Prince of Wales Hospital (PWH) Real‐world Analysis of People with Drug‐Resistant Epilepsy (DRE) on PERampanel (WRAPPER) study assessed effectiveness and tolerability of adjunctive perampanel in people with DRE attending PWH.MethodsThis was a prospective single‐center real‐world observational study involving 70 people with DRE between July 2016 and June 2021. A post hoc analysis after the initial study period of 16 weeks assessed outcomes for an extended period up to 52 weeks.ResultsAfter 16 weeks, median dose of perampanel was 2 mg (IQR 24 mg). 50% responder rates were 40.0%, 41.5%, and 48.7% at 16, 26, and 52 weeks. Seizure freedom was 12.9%, 20.7%, and 25.6% at 16, 26, and 52 weeks. Monthly seizure frequency reduced from 3.0 (IQR 3.0–6.6) at baseline to 2.0 (IQR 2.0–6.0, p = 0.005) at 16 weeks; 2.0 (IQR 2.0–5.0, p = 0.01) at 26 weeks; and 2.0 (IQR 0.0–4.0, p = 0.018) at 52 weeks. Older age predicted 50% responders (OR 1.08, 95% CI 1.01–1.14, p = 0.048).At 16 weeks, 51.4% (36/70) had treatment‐emergent adverse effects (TEAEs). Most common was seizure exacerbation at 35.7% (25/70) followed by fatigue at 15.7% (11/70). NPI‐12 and ZBI scores indicated no increase in neuropsychiatric symptoms on perampanel.SignificanceLow‐dose 2–4 mg adjunctive perampanel for people with DRE conferred appreciable improvements in seizure reduction without significant neuropsychiatric adverse effects in the real‐world setting at a tertiary center in Hong Kong and had better antiseizure effect with advancing age.Plain Language SummaryThis real‐world study from Hong Kong found low‐dose perampanel was effective and tolerable for people with drug‐resistant epilepsy. Furthermore, perampanel was also potentially more effective with advancing age.

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

Nakai,

Nishimoto,

Higashibeppu

et al. 2024

ObjectiveTo 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.MethodsThe 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.ResultsOverall, 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%).SignificanceIn real‐world clinical conditions, efficacy and tolerability for PER combination therapy were observed at low PER doses for the PSE, BTRE, and PTE subpopulations.Plain Language SummaryTo 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.