<p>An Evidence-Based Review On The Use Of Perampanel For The Treatment Of Focal-Onset Seizures In Pediatric Patients</p>

Abstract

Perampanel, a non-competitive AMPA receptor antagonist, is a once-daily oral antiepileptic drug approved for the treatment of focal seizures and primary generalized tonicclonic seizures in children 12 years of age and over. We conducted a systematic review of the data on perampanel in children and adolescents with focal-onset seizures. We found 21 published papers on the pediatric use of perampanel for focal-onset seizures, including 9 papers on clinical trials and ancillary studies of these trials, of which 2 focused on pharmacokinetics, 1 was a metaanalysis, and 9 were real-life studies (1 was prospective). Perampanel, as an adjunctive treatment for uncontrolled focal-onset seizures, results in an improvement of seizure control with a generally good safety profile. Evidence-based data are currently available for children 12 years of age and over. Higher amounts of perampanel might be required in patients taking enzymeinducing antiepileptic drugs. The most common adverse events are somnolence, dizziness and behavioral adverse events. The latter seems more frequent in adolescents than in adults and in adolescents with preexisting behavioral comorbidities. Current studies did not identify any shortterm impact of perampanel on cognitive functions. Its long half-life allows once-daily administration. Real-life studies further established that a decrease of the dose frequently resolves adverse events, as demonstrated in pivotal studies. Pharmacokinetic and safety studies are still ongoing in the younger population, down to 4 years of age, in order to apply for approval in this age group.

Src/CK2/PTEN-Mediated GluN2B and CREB Dephosphorylations Regulate the Responsiveness to AMPA Receptor Antagonists in Chronic Epilepsy Rats

“…In addition, perampanel (a non-competitive AMPA receptor antagonist) results in an improvement of uncontrolled focal-onset seizure control as an add-on treatment. Thus, perampanel is an AED approved for the treatment of focal seizures and primary generalized tonic-clonic seizures in patients >12 years old [ 28 ]. In animal study, perampanel (2 mg/kg) effectively increases the after-discharge threshold in a rapid kindling model using immature rats, although it shows no effect on the number of stage 4–5 seizures in mature rats (postnatal 60 days) [ 29 ].…”

Young children with multidrug-resistant epilepsy and vagus nerve stimulation responding to perampanel: A case report

“…PER is the first AED targeting AMPA receptors, which was approved by the United States Food and Drug Administration (FDA) to treat partial-onset seizures with or without secondarily generalized seizures for adult patients with epilepsy in September 2018[ 2 , 3 ]. Its great cognitive profile, ease of use of the titration scheme and the once-daily oral regimen give it advantages over other AEDs.…”

“…The AEs of PER mainly include dizziness, irritability, fatigue, aggressiveness, suicide, nausea and weight gain[ 2 ]. Dizziness and somnolence are the most common AEs[ 3 ]. Because of some severe mental and behavioral adverse reactions, including aggressiveness, irritability, homicidal behavior, and threats, PER was given a black box warning by the FDA when it was first approved[ 12 ].…”

Psychobehavioural and Cognitive Adverse Events of Anti-Seizure Medications for the Treatment of Developmental and Epileptic Encephalopathies

“…Although it has been suggested that PBAEs may be affected by dose [ 132 , 187 ], other studies have reported the occurrence of PBAEs over a wide range of doses [ 188 ]. In addition, PER-associated aggressive behaviour may be more frequent in adolescents than adults [ 189 , 190 ]. Of note, aggressive behaviour has been reported to occur months or even years after initiating PER [ 191 ].…”