Clinical profiles associated with serum perampanel concentrations in children with refractory epilepsy

Ishikawa, Nobutsune; Tateishi, Yuichi; Tani, Hiroo; Kobayashi, Yoshiyuki; Kobayashi, Masao

doi:10.1016/j.yebeh.2019.02.004

Cited by 27 publications

(46 citation statements)

References 16 publications

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“…13 observational studies N = 3 [38]; N = 8 [21]; N = 8 [15]; N = 4 [40]; N = 115 [14]; N = 18 [45]; N = 17 [18]; N = 6 [35]; N = 9 [39]; N = 4 [46]; N = 4 [16]; in refractory childhood epilepsy [15] to 100% in refractory JME [16] PGTCS-free rates from 0% in Dravet syndrome [21] and refractory childhood epilepsy [40] to 88% and 100% in JME [16] Not extractable in 8 studies No worsening in 2 studies [38,46] Reported in 1/7 and 2/4 children with refractory epilepsy [15,40] ≥ 10% increase from baseline reported in 6/115 patients with IGE (5.2%) at…”

Section: Absence Seizuresmentioning

confidence: 99%

“…The median frequency of absence seizures at baseline was 13.0 in the perampanel group (range 0. [11] and in 70% (7/10) with Lafora disease [12] Reduction in myoclonus severity in PME [11] Subjective myoclonic seizure worsening in at least 1 patient (and ≤ 4) led to discontinuation [11] AE rates 45-80% [11,12] Discontinuation due to AEs in 22% and 30% [11,12] 14 observational studies reported outcomes in patients or subgroups with myoclonic seizures N = 48 IGE [14]; N = 31 [18]; N = 18 [35]; N = 12 PME [19]; N = 11 [45]; 39]; N = 5 JME [16]; N = 3 Dravet [21]; [20]; N = 3 [38]; N = 3 [46]; N = 2 [40]; N = 1 [51] [45]; [46]; N = 4 [15]; N = 4 [40]; N = 3 Dravet [21]; [38]; N = 3 JME [16]; S1, see ESM 4). Results from smaller studies were broadly consistent, with high rates of seizure freedom (Table 4).…”

Section: Absence Seizuresmentioning

confidence: 99%

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Exploring the Evidence for Broad-Spectrum Effectiveness of Perampanel: A Systematic Review of Clinical Data in Generalised Seizures

et al. 2021

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Background The effectiveness of adjunctive perampanel has not been systematically assessed in seizure types other than its approved indications of focal seizures and primary generalised tonic-clonic seizures (PGTCS) in idiopathic generalised epilepsies (IGEs). Objective We aimed to identify and review available evidence on outcomes with perampanel in generalised seizures and epilepsies to examine its potential as a broad-spectrum anti-seizure medication. Methods Bibliographic databases of publications, clinical trials, and conference abstracts were searched up to August 2020 to identify studies reporting seizure or safety outcomes in patients of any age, with any type of epilepsy-associated generalised seizures treated with perampanel. Data extracted from selected records were tabulated by seizure type and syndrome, and analysed qualitatively (PROSPERO protocol CRD42020201564). Results Ninety-one reports met inclusion criteria and were selected: 15 reports of 1 randomised controlled trial (RCT), 8 reports of 4 non-randomised interventional studies, 37 reports of observational studies, 21 case reports and 10 systematic reviews and meta-analyses. Extracted data included 359 patients with PGTCS of any aetiology, 251 with myoclonic seizures, 112 with absence seizures, 50 with tonic seizures and 32 children with epileptic spasms. The most commonly reported epilepsy type was IGE (N = 378) and the most common syndromes were juvenile myoclonic epilepsy (N = 92), progressive myoclonic epilepsies (N = 59) and absence epilepsies (N = 43). The RCT provided Class I evidence of the efficacy and tolerability of adjunctive perampanel for PGTCS in patients aged ≥ 12 years with IGE. Data from other studies provides weaker (observational) evidence of its effectiveness in multiple generalised seizure types, including myoclonic, absence and tonic seizures. There were no patterns suggesting seizure worsening or aggravation in any seizure or epilepsy type. Conclusions The identified studies suggest the potential of perampanel as a broad-spectrum antiseizure medication. Much of the available data, however, come from non-randomised, non-controlled studies and are open to high risk of bias. Further studies are warranted to provide more robust evidence.

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Section: Absence Seizuresmentioning

confidence: 99%

Section: Absence Seizuresmentioning

confidence: 99%

Exploring the Evidence for Broad-Spectrum Effectiveness of Perampanel: A Systematic Review of Clinical Data in Generalised Seizures

et al. 2021

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“…PER is known to be extensively metabolized by the hepatic CY-P3A4. Concomitant drugs that modulate CYP3A4 activity can reduce the half-life of PER by 50% to 70%, resulting in lower PER serum concentrations [13,29,35]. However, EIAEDs had no significant effects on the efficacy and adverse event rate in this study.…”

Section: Discussionmentioning

confidence: 57%

“…Overexpression of AMPA receptors is also observed in the hippocampal and neocortical tissue of patients with epilepsy [11,12]. PER is mainly metabolized in the liver by cytochrome P450 (CYP3A4/6); therefore, enzyme-inducing antiepileptic drugs (EIAEDs), such as carbamazepine (CBZ), oxcarbazepine (OXC), and phenytoin (PHT), can reduce its concentrations up to 50% to 60% [13] and concomitant use of EIAEDs has been reported as a clinical factor for poor response to PER and concomitant use of EIAEDs has been reported as a clinical factor for poor response to PER [14]. PER was initially approved for adjunctive treatment of focal seizures (with or without secondarily generalized seizures) in patients with epilepsy aged ≥12 years [15].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Tolerability of Low-Dose Perampanel in Patients with Childhood-Onset Intractable Epilepsy

et al. 2019

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The aim of this study was to evaluate the efficacy and tolerability of perampanel as adjunctive therapy in childhood-onset refractory epilepsy. Methods: We retrospectively reviewed the medical records of 110 patients who were treated with perampanel in Asan Medical Center children's hospital. Two patients with poor compliance were excluded and 108 patients were enrolled. The clinical characteristics were reviewed, and the total seizure frequency before and after the add-on of perampanel was analyzed. Results: The mean age of the patients (64 males) was 20.2 years (range, 10.5 to 35.6). The mean maintenance dose was 4.8 mg/day (2 to 10 mg). Eight patients (7.4%) achieved seizure freedom and 35 (32.4%) achieved a seizure reduction of ≥50%. Among them, three patients achieved seizure freedom with only 2 mg/day of perampanel. There was no significant difference in sex, age at seizure onset, duration of epilepsy, use of concomitant enzyme-inducing antiepileptic drugs, number of concomitant antiepileptic drugs, and adverse events between responders and non-responders. The retention rate was up to 68.0% in the first year and 59.5% in the second year of the study. Thirty-four patients (31.5%) reported adverse events: violence, somnolence, dizziness, drooling, weight gain, insomnia, and vomiting. There was no contributing factor for the adverse events, including sex, age, and the number of concomitant antiepileptic drugs and enzyme-inducing antiepileptic drugs when comparing the adverse event present group with the adverse event absent group. Conclusion: Low-dose perampanel showed reasonable efficacy and tolerability in patients with refractory childhood-onset epilepsy. Further validation with pharmacokinetic studies is needed.

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“…Missing are serum levels of ASDs applied [5]. In addition, knowing the family history is crucial to assess if the variant occurred de novo or was inherited.…”

mentioning

confidence: 99%

Polypharmacy with perampanel for drug-resistant, focal non-convulsive status epilepticus as a manifestation of a stroke-like episode in MELAS

Finsterer

2019

Epilepsy & Behavior Reports

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Clinical profiles associated with serum perampanel concentrations in children with refractory epilepsy

Cited by 27 publications

References 16 publications

Exploring the Evidence for Broad-Spectrum Effectiveness of Perampanel: A Systematic Review of Clinical Data in Generalised Seizures

Exploring the Evidence for Broad-Spectrum Effectiveness of Perampanel: A Systematic Review of Clinical Data in Generalised Seizures

Efficacy and Tolerability of Low-Dose Perampanel in Patients with Childhood-Onset Intractable Epilepsy

Polypharmacy with perampanel for drug-resistant, focal non-convulsive status epilepticus as a manifestation of a stroke-like episode in MELAS

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