PracticeUpdate: Neurology - Winter 2018

" [P]erampanel coadministered with an enzyme-inducing antiepileptic drug (carbamazepine, eslicarbazepine, oxcarbazepine, phenytoin) was associated with less efficacy than non-enzyme- inducing antiepileptic drugs due to increased clearance. " ANZAN 2018 17

In the double-blind studies, patients (≥12 years of age) with partial seizures with or without secondarily generalized seizures, who were receiving one to three antiepi- leptic drugs at baseline were randomized to placebo or 2–12 mg perampanel daily for 19 weeks. In the open-label extension, patients received perampanel ≤12 mg daily for ≤272 weeks. Efficacy assessments included median percent change in the frequency of secondarily generalized seizures in 28 days, and 50% and 75% responder and sei- zure-freedom rates, respectively. For patients with secondarily generalized seizures at baseline prior to receiving per- ampanel, 564 patients participated in the double-blind studies and 388 received per- ampanel for at least 1 year in the open-label extension study. In the double-blind studies, perampanel coadministered with an enzyme-inducing antiepileptic drug (carbamazepine, eslicar- bazepine, oxcarbazepine, phenytoin) was associated with less efficacy than non-en- zyme-inducing antiepileptic drugs due to increased clearance. This reduced efficacy

Patients may have received more than one of these baseline antiepileptic drugs. The most common reasons for discontinuing were adverse events, other, and patient choice: • Lamotrigine was discontinued due to patient choice by 6 of 34 patients receiving >4–8 mg daily and due to adverse events or other by 3 of 19 patients receiving >8–12 mg daily • Levetiracetam was discontinued due to patient choice by 5 of 27 patients receiving >4–8 mg daily and due to adverse events by 2 of 10 patients receiving >8–12 mg daily • Topiramate was discontinued due to other by 3 of 15 patients receiving >4–8 mg daily and due to adverse events or other by 1 of 6 patients who received >8–12 mg daily for both • Valproic acid was discontinued due to patient choice by 6 of 38 patients receiving >4–8 mg daily and due other by 4 of 17 patients receiving >8–12 mg daily • Zonisamide was discontinued due to patient choice or other by 2 of 10 patients receiving >4–8 mg daily for both. No discontinuations were recorded among patients who received >8–12 mg daily Patient-reported treatment-emergent adverse events ranged from: 88.2% (lamotrigine) to 93.3% (topiramate) for per- ampanel >4–8 mg daily and 70.6% (valproic acid) to 100.0% (topiramate and zonis- amide) for perampanel >8–12 mg daily. The most common treatment-emergent adverse event was dizziness. Dr. O’Brien concluded that in this post hoc analysis, the primary reasons for discontinuation and the incidence of treat- ment-emergent adverse events differed between the most common baseline antiepileptic drug subgroups and the per- ampanel dose range, though types of treatment-emergent adverse events were similar. The data provided additional information on the safety of adjunctive perampanel in patients with idiopathic generalized epi- lepsy. www.practiceupdate.com/c/68176

was particularly evident at higher doses, though the differences were still greater than placebo in the open-label extension study. Concomitant administration of both non-enzyme-inducing antiepileptic drugs and enzyme-inducing antiepileptic drugs was associated with sustained efficacy, with slightly better efficacy during the first, second, and third years of peram- panel exposure for non-enzyme-inducing antiepileptic drugs than enzyme-inducing antiepileptic drugs. Dr. Ko concluded that perampanel demon- strated good and sustained long-term efficacy against secondarily generalized seizures. Considering the recent FDA approval of perampanel as monotherapy for partial seizures, non-enzyme-inducing antiepi- leptic drugs data may be more relevant to consider when perampanel is used as a single agent (no other enzyme-inducing antiepileptic drug) while real-world data and experience are accumulated. Terence J O'Brien, MD, MB, of Monash University in Melbourne, Victoria, and col- leagues set out to assess the effect of common concomitant antiepileptic drugs during adjunctive treatment with peram- panel. They performed a post hoc analysis from the open-label extension of a phase III study in patients with idiopathic gener- alized epilepsy. The analysis assessed the effects of the most common concomitant baseline antie- pileptic drugs on discontinuation rates and treatment-emergent adverse event inci- dence during adjunctive treatment with perampanel in patients age ≥12 years with idiopathic generalized epilepsy and primary generalized tonic-clonic seizures in the open-label extension phase of study 332. Patients who completed the double-blind study were eligible to receive perampanel ≤12mg daily during the open-label exten- sion (6-week blinded conversion period; ≤136 weeks of maintenance). Dr. O’Brien reported results for perampanel >4–8 mg and >8–12 mg daily. The most common concomitant base- line antiepileptic drugs were valproic acid (n=55), lamotrigine (n=53), levetiracetam (n=37), topiramate (n=21), and zonisamide (n=12).

VOL. 3 • NO. 3 • 2018