Perampanel for focal epilepsy: insights from early clinical experience

Abstract

Perampanel is approved for adjunctive therapy of focal epilepsy with or without secondarily generalized seizures in patients aged >12 years. This narrative review uses real‐world and clinical trial data to elucidate perampanel's role in the clinic. Audit data show good tolerability with perampanel and higher freedom‐from‐seizure rates in elderly vs younger patients. When using perampanel in elderly patients, special attention should be given to comorbidities and co‐medication to avoid potential interactions or adverse events. Slower titration is generally recommended, and seizure control should be reassessed at a dose of 4 mg before further dose increases. Perampanel efficacy is similar in adolescents and adults; however, somnolence, nasopharyngitis, and aggression are more frequent in adolescents vs the overall population. Individualized and slow‐dose titration can minimize adverse events. Low serum concentrations of perampanel may occur in patients also receiving some enzyme‐inducing anti‐epileptic drugs; a perampanel dose increase may be required. Adverse events of importance with perampanel include dizziness; anger, aggression, and hostile behavior (particularly in adolescents); and falls (particularly in patients >65 years). An individualized approach to dosing, including slower up‐titration and bedtime dosing, reduces dizziness risk. Other drugs may cause or aggravate dizziness; reducing concomitant drugs may be necessary when up‐titrating perampanel. It would seem clinically appropriate to give due consideration to avoiding use in patients with a history of anger or hostile/aggressive behavior. The possibility of such behaviors should be discussed with patients before starting perampanel, with monitoring during up‐titration. Slower up‐titration of perampanel in older patients helps reduce fall risk.

Reflections on the Use of Perampanel in Epilepsy – Lessons from the Clinic and Real-world Evidence

“…In the Salzburg prospective audit, the efficacy and tolerability of perampanel in 20 elderly patients (mean age 69.8 years) were compared with that in 65 younger patients (mean age 36.8 years). 33 Over 57 months, 35% (7/20) of elderly patients were seizure free compared with 13.8% (9/65) of younger patients (p=0.009). In the same line, in a multicentre, retrospective observational study with an overall cohort of 464 patients with refractory focal epilepsy of whom 25 were aged ≥65 years, age ≥65 was a predictor of seizure freedom at 12 months.…”

“…33 However, few treatment options are available for patients with PGTC seizures and more real-world evidence is needed. A recent retrospective, single-centre post-marketing study review of medical records includ patients with focal, secondarily generalised, PGTC, and other seizures, 34 including data for 101 patients taking perampanel.…”

Successful treatment of epilepsia partialis continua due to Rassmussen encephalitis with perampanel

“…In a recent narrative review on real world clinical data of PER response rates ranging from 9% to 89% in focal epilepsies were reported (Trinka et al, 2015b). We previously published two other treatment episodes of EPC due to stroke (Rösche et al, 2014) and vascular dementia with a possible effect of PER.…”

Analysis of the clinical experience with perampanel in the Moscow Region: Efficacy, tolerability, individual choice priorities

“…Несомненно, данные исследований зависят от особенно-стей выборки больных, и вопрос о выборе дозы должен ре-шаться индивидуально, а основу решения будет составлять баланс клинической эффективности и переносимости. В соответствии с данными литературы, осторожность тит- рования ПЕР продиктована в основном стремлением ниве-лировать дозозависимые НЯ, прежде всего -аффективного ряда (агрессия, тревога, психоз) [16]. В нашем исследовании подобная симптоматика стала причиной отмены ПЕР у 5 (17,8%) больных, принимавших невысокие дозы ПЕР: 2 мг/сут (n=2), 4 мг/сут (n=1) и 6 мг/сут (n=2).…”