Perampanel in patients with refractory and super‐refractory status epilepticus in a neurological intensive care unit: A single‐center audit of 30 patients

Rohracher, Alexandra; Kalss, Gudrun; Neuray, Caroline; Höfler, Julia; Dobesberger, Judith; Kuchukhidze, Giorgi; Kreidenhuber, Rudolf; Florea, Cristina; Thomschewski, Aljoscha; Novak, Helmut F.; Pilz, Georg; Leitinger, Markus; Trinka, Eugen

doi:10.1111/epi.14494

Cited by 34 publications

(46 citation statements)

References 28 publications

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“…[19][20][21][22] Rohracheretalreportedtreatmentresponsein5/30(16.7%)perampanel-treated patients with RSE and SRSE, of whom two received higher doses (20 and 24 mg); however, decreased bioavailability and late administration may have diminished the potential effects of perampanel. [19][20][21][22] Rohracheretalreportedtreatmentresponsein5/30(16.7%)perampanel-treated patients with RSE and SRSE, of whom two received higher doses (20 and 24 mg); however, decreased bioavailability and late administration may have diminished the potential effects of perampanel.…”

Section: Discussionmentioning

confidence: 99%

“…Studies in the rat lithium-pilocarpine model of SE have suggested that perampanel may have efficacy in terminating prolonged seizures 17,18 while providing neuroprotection, though the level of neuroprotective effects varied by region. 15 However, while clinical cases of perampanel use for the treatment of patients with SE have been reported, [19][20][21][22] there are currently few published case reports assessing the effectiveness of perampanel in SE, as reviewed previously. Furthermore, modified expres-sionoftheAMPAsubunitsGluA1andGluA2andalteredCa 2+ permeability have been observed in animal models of SE.…”

Section: Intermsoftheunderlyingpathophysiologysemightarisefrommentioning

confidence: 99%

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Perampanel for treatment of status epilepticus in Austria, Finland, Germany, and Spain

et al. 2019

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Objective Novel treatments are needed to control treatment‐resistant status epilepticus (SE). We report a summary of clinical cases where perampanel was used in established SE, refractory SE (RSE), or super‐refractory SE (SRSE). Methods Medical records were retrospectively reviewed for perampanel administration in SE at five European hospitals between 2011 and 2015. Results Of 1319 patients identified as experiencing SE, 52 (3.9%) received perampanel. Median latency from SE onset to perampanel initiation was 10 days. Patients with SE had previously failed benzodiazepines (when received) and a median of five other antiepileptic drugs (AEDs). Median initial perampanel dose was 6 mg/d, up‐titrated to a median maximum dose of 10 mg/d. Perampanel was the last drug added in 32/52 (61.5%) patients, with response attributed to perampanel in 19/52 (36.5%) patients. A greater proportion of perampanel non‐responders had SRSE (51.5%; 17/33) vs perampanel responders (31.6%; 6/19), and had failed a higher mean number of AEDs before initiating perampanel (5.9 vs 5.1, respectively). Most commonly reported adverse effects during perampanel treatment were dizziness (n = 1 [1.9%]) and somnolence (n = 1 [1.9%]). No serious adverse effects were documented, and none led to discontinuation of perampanel. Conclusions Perampanel was administered to patients with established SE, RSE, or SRSE at greater initial doses than those administered in clinical practice to patients with epilepsy. The SE cases reported here represent a refractory and heterogeneous population, and rate of seizure cessation attributed to perampanel treatment (36.5%) represents a notable response. These data should be confirmed in a larger patient population.

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Section: Discussionmentioning

confidence: 99%

Section: Intermsoftheunderlyingpathophysiologysemightarisefrommentioning

confidence: 99%

Perampanel for treatment of status epilepticus in Austria, Finland, Germany, and Spain

et al. 2019

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“…Findings from phase III studies suggest that PER 4 mg is probably the lowest effective dose in patients with partial‐onset seizures, with increased efficacy at the 8‐mg and 12‐mg doses . Review of the literature shows five articles on the use of this agent in SE (Table ) . One study analyzed PER use in 12 patients with RSE in a single neurology ICU in Austria.…”

Section: Discussionmentioning

confidence: 99%

“…30 patients that received perampanel as add‐on treatment in refractory and super‐refractory SE from Sept 2012 and Feb 2018…”

Section: Discussionmentioning

confidence: 99%

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Use of Newer Anticonvulsants for the Treatment of Status Epilepticus

et al. 2019

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Status epilepticus (SE) has a high mortality rate and is one of the most common neurologic emergencies. Fast progression of this neurologic emergency and lack of response to traditional antiepileptic drugs (AEDs) in most cases has challenged clinicians to use new agents. This article evaluates the efficacy and safety of AEDs released to the market after 2000 for SE, refractory status epilepticus (RSE), and super‐refractory status epilepticus (SRSE). The PubMed database was searched for clinical trials published between January 2000 and July 2018 using the search terms status epilepticus, refractory status epilepticus, super refractory status epilepticus, brivaracetam, clobazam, cannabidiol, eslicarbazepine, lacosamide, perampanel, rufinamide, stiripentol, and zonisamide. Trials that evaluated these agents in adults with SE, RSE, and SRSE were included. Brivaracetam use was identified in two retrospective reviews with success rates of 27% and 57%. One unsuccessful case report of cannabidiol use in SE was found. Four clobazam studies were identified in SE and RSE with success rates ranging from 25–100%. No evidence for the use of eslicarbazepine and zonisamide was found. Using the search terms for lacosamide identified 38 articles: 1 systematic review, 5 prospective studies, 15 retrospective reviews, and 17 case reports. Success rates and dosing varied, but studies that included focal or partial types of SE showed higher success rates. Five articles were identified regarding perampanel use in this setting. Three were retrospective reviews with success rates ranging from 17–60%, and two were case reports. Only one case report regarding the use of rufinamide was found; rufinamide titrated up to 4.4 mg/day allowed discontinuation of barbiturate and clobazam. One case report and two case series of stiripentol were found with reported efficacy between 60% and 100% in SRSE. Evidence is currently insufficient to support the use of these agents in this setting.

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Perampanel in real‐world clinical care of patients with epilepsy: Interim analysis of a phase IV study

et al. 2020

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Objective To assess the retention rate, efficacy, safety, and dosing of perampanel administered to patients with epilepsy during routine clinical care in the retrospective phase IV, PROVE Study (NCT03208660). Methods Exposure, efficacy, and safety data were obtained from the medical records of patients initiating perampanel after January 1, 2014, across 29 US study sites. The cutoff date for this interim analysis was October 10, 2018. The primary efficacy endpoint was retention rate. Secondary efficacy endpoints included median percent changes in seizure frequency, seizure‐freedom rate, and overall investigator impression of seizure effect. Results All enrolled patients (N = 1121) received perampanel. Mean (standard deviation [SD]) cumulative duration of exposure to perampanel was 16.6 (14.7) months; overall mean (SD) daily perampanel dose was 5.7 (2.7) mg. Perampanel uptitration occurred weekly (21.1%), biweekly (23.8%), every 3 weeks (1.5%), other (43.3%), and unknown (10.3%). Across the Safety Analysis Set (N = 1121), retention rate on perampanel at 24 months was 49.5% (n = 319/645). At 12 months, the median reduction in seizure frequency per 28 days from baseline in the small number of patients for whom data were available was 75.0% (n = 85), and 30/85 (35.3%) patients were seizure free. Based on investigator impression at the end of treatment, improvement, no change (ie, stable), or worsening of seizures was reported in 54.3%, 33.7%, and 12.0% of patients, respectively. Treatment‐emergent adverse events occurred in 500 (44.6%) patients; the most common were dizziness (9.2%), aggression (5.4%), and irritability (4.5%). Serious treatment‐emergent adverse events occurred in 32 (2.9%) patients. Significance Favorable retention and sustained efficacy were demonstrated for ≥12 months following initiation of perampanel during routine clinical care in patients with epilepsy.

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Perampanel in patients with refractory and super‐refractory status epilepticus in a neurological intensive care unit: A single‐center audit of 30 patients

Cited by 34 publications

References 28 publications

Perampanel for treatment of status epilepticus in Austria, Finland, Germany, and Spain

Perampanel for treatment of status epilepticus in Austria, Finland, Germany, and Spain

Use of Newer Anticonvulsants for the Treatment of Status Epilepticus

Perampanel in real‐world clinical care of patients with epilepsy: Interim analysis of a phase IV study

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