Pediatric adverse reactions to antiseizure medications – An analysis of data from the Italian spontaneous reporting system (2001–2019)

Franco, Valentina; Cutroneo, Paola Maria; Arena, Ignazio Giuseppe; Cicala, Giuseppe; Marchione, Pasquale; Spina, Edoardo; Perucca, Emilio

doi:10.1016/j.yebeh.2021.107989

Cited by 16 publications

(10 citation statements)

References 30 publications

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“…Overall, the comparison of the treatment regimens of patients carrying a KCNA1 mutation confirms the need of a patient-centric approach and supports the use of sodium channel blockers, such as carbamazepine, lacosamide, lamotrigine, to improve the course of the disease [ 34 , 38 ]. Caution must be taken when using sodium valproate in children due to possible seizure aggravation and clonazepam and oxcarbazepine due to motor coordination disturbances [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical and Functional Study of a De Novo Variant in the PVP Motif of Kv1.1 Channel Associated with Epilepsy, Developmental Delay and Ataxia

Dinoi

Morin

Conte

et al. 2022

IJMS

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Mutations in the KCNA1 gene, encoding the voltage-gated potassium channel Kv1.1, have been associated with a spectrum of neurological phenotypes, including episodic ataxia type 1 and developmental and epileptic encephalopathy. We have recently identified a de novo variant in KCNA1 in the highly conserved Pro-Val-Pro motif within the pore of the Kv1.1 channel in a girl affected by early onset epilepsy, ataxia and developmental delay. Other mutations causing severe epilepsy are located in Kv1.1 pore domain. The patient was initially treated with a combination of antiepileptic drugs with limited benefit. Finally, seizures and ataxia control were achieved with lacosamide and acetazolamide. The aim of this study was to functionally characterize Kv1.1 mutant channel to provide a genotype–phenotype correlation and discuss therapeutic options for KCNA1-related epilepsy. To this aim, we transfected HEK 293 cells with Kv1.1 or P403A cDNAs and recorded potassium currents through whole-cell patch-clamp. P403A channels showed smaller potassium currents, voltage-dependent activation shifted by +30 mV towards positive potentials and slower kinetics of activation compared with Kv1.1 wild-type. Heteromeric Kv1.1+P403A channels, resembling the condition of the heterozygous patient, confirmed a loss-of-function biophysical phenotype. Overall, the functional characterization of P403A channels correlates with the clinical symptoms of the patient and supports the observation that mutations associated with severe epileptic phenotype cluster in a highly conserved stretch of residues in Kv1.1 pore domain. This study also strengthens the beneficial effect of acetazolamide and sodium channel blockers in KCNA1 channelopathies.

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Section: Discussionmentioning

confidence: 99%

Clinical and Functional Study of a De Novo Variant in the PVP Motif of Kv1.1 Channel Associated with Epilepsy, Developmental Delay and Ataxia

Dinoi

Morin

Conte

et al. 2022

IJMS

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“…Thus, pharmacokinetic or pharmacodynamic interactions between perampanel and levetiracetam may account for the better outcome observed in levetiracetam-treated patients, however, further studies are needed to confirm this. • 861 disorders, including irritability, aggression, agitation, anxiety, and hyperactivity disorder compared with other AEDs in paediatric patients with epilepsy [35]. Thus, the risk of AEs, such as irritability and aggression, is likely to be increased in cases of concomitant perampanel and levetiracetam.…”

Section: Discussionmentioning

confidence: 99%

“…The packaging of perampanel warns of serious psychiatric and behavioural reactions, including aggression, hostility, irritability, anger, and homicidal ideation, as required by the Food and Drug Administration [4]. Levetiracetam demonstrates a distinct pattern of association with mood and behavioural disorders, including irritability, aggression, agitation, anxiety, and hyperactivity disorder compared with other AEDs in paediatric patients with epilepsy [35]. Thus, the risk of AEs, such as irritability and aggression, is likely to be increased in cases of concomitant perampanel and levetiracetam.…”

Section: Discussionmentioning

confidence: 99%

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

Qu¹,

Dai²,

Chen³

et al. 2021

Epileptic Disorders

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Objective. 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. Methods. 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. Results. 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 4 mg (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. Significance. 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.

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“…They used a case–control study approach to compare the Parkinson disease and control groups in the UK Biobank database, and found that ASMs (valproate, lamotrigine, carbamazepine and levetiracetam) were associated with an 80% increased risk of developing Parkinson disease 5 . A postmarketing study based on the Italian spontaneous reporting system showed that 6.6% of children with ASMs developed MDs 6 . However, evidence of new first‐ or second‐line ASM‐related MDs is currently scarce, with most limited to case reports.…”

Section: Introductionmentioning

confidence: 99%

“…5 A postmarketing study based on the Italian spontaneous reporting system showed that 6.6% of children with ASMs developed MDs. 6 However, evidence of new first-or secondline ASM-related MDs is currently scarce, with most limited to case reports. Therefore, there is a need to conduct more pharmacovigilance on more ASMs to raise greater public awareness of MDs related to ASMs.…”

mentioning

confidence: 99%

Movement disorders associated with antiseizure medications: A real‐world disproportionality analysis of the Food and Drug Administration Adverse Event Reporting System

Zhou

Wei

Chen

et al. 2023

Brit J Clinical Pharma

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AimsPatients with epilepsy often require long‐term use of antiseizure medications (ASMs) to control their seizures. However, movement disorders (MDs) related to ASMs can significantly impact their quality of life. This study aims to analyse MDs related to ASMs in the Food and Drug Administration Adverse Event Reporting System database to provide recommendations for safe medication.MethodsAll adverse drug reactions associated with 26 marketed ASMs in Food and Drug Administration Adverse Event Reporting System were extracted for analysis. Disproportionality analyses were used to assess the association between ASMs and MDs, and signal colour scale maps were created to identify potential ASM–MD safety signals.ResultsA total of 1921 cases experienced MDs while taking ASMs were included. A higher prevalence of MDs was observed in females compared to males. The association between specific MDs with ASMs was revealed, including known and unknown MDs such as tremors, Parkinson and paralysis. Lamotrigine and carbamazepine exhibited multiple significant MDs, while levetiracetam and pregabalin were linked to the earlier onset of MDs. Generally, higher doses were linked to a higher incidence of MDs.ConclusionMDs were the most obvious adverse drug reactions in the nervous system triggered by using ASMs. Fourteen drugs exhibited positive signals for MDs, including some not previously reported. Conversely, 12 ASMs were deemed to have a lower possibility of inducing MDs. The incidence of MDs can be mitigated by selecting appropriate ASMs for epileptic patients. These findings enhance our understanding of the relationship between ASMs and MDs.

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Pediatric adverse reactions to antiseizure medications – An analysis of data from the Italian spontaneous reporting system (2001–2019)

Cited by 16 publications

References 30 publications

Clinical and Functional Study of a De Novo Variant in the PVP Motif of Kv1.1 Channel Associated with Epilepsy, Developmental Delay and Ataxia

Clinical and Functional Study of a De Novo Variant in the PVP Motif of Kv1.1 Channel Associated with Epilepsy, Developmental Delay and Ataxia

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

Movement disorders associated with antiseizure medications: A real‐world disproportionality analysis of the Food and Drug Administration Adverse Event Reporting System

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