What is the role of perampanel (Fycompa) in the treatment of epilepsy?

Updated: Jan 28, 2020
  • Author: Juan G Ochoa, MD; Chief Editor: Selim R Benbadis, MD  more...
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Answer

In October 2012, the US Food and Drug Administration (FDA) approved  perampanel (Fycompa) as adjunctive treatment for partial-onset seizures (with or without secondary generalized seizures) and in June 2015 for primary generalized tonic-clonic seizures in adults or children aged 12 years or older. Perampanel is a noncompetitive antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA).

The approval for partial-onset seizures was based on 3 randomized, double-blind, placebo-controlled, multicenter trials in 1,480 patients who were not adequately controlled with 1 to 3 concomitant AEDs. A dose-ranging study by Krauss et al showed statistically significant declines in partial-onset seizure frequencies for the perampanel groups compared with placebo. Mean percentage declines for perampanel were 13.6% for 2 mg/day (P = .4197), 23.3% for 4 mg/day (P = .0026), 30.8% for 8 mg/day (P< .0001), and a 10.7% decrease for placebo. [80] Additional studies of higher perampanel doses (ie, 8 mg/day and 12 mg/day) improved seizure control in patients with uncontrolled partial-onset seizures. [81, 82]

Approval for PGTC seizures was based on a Phase 3, randomized, double-blind, placebo-controlled clinical trial (n = 162) in patients taking up to 3 antiepileptic drugs. Patients treated with perampanel (n=81) achieved a 76% median reduction in PGTC seizure frequency, which was statistically significant compared to 38% with placebo (n=81). Additionally, 64% of patients in the treatment arm experienced a >50% reduction in PGTC seizure frequency compared with placebo which attained a 40% reduction. [83]

Perampanel was assigned a DEA schedule III. The prescribing information includes a boxed warning that describes serious or life-threatening psychiatric and behavioral adverse reactions, including aggression, hostility, irritability, anger, and homicidal ideation and threats. [84] Common adverse effects include dizziness (up to 43%), somnolence, headache, fatigue, and irritability.

In the absence of other AEDs that induce CYP enzymes, the initial dose is 2 mg PO at bedtime. After 1 week, the dose may be increased by at least weekly intervals to 4-8 mg/day (titrate more slowly, by at least 2-week intervals in elderly persons). The target dosage range is 8-12 mg/day for partial onset seizures and 8 mg/day for tonic-clonic seizures (may increase to 12 mg/day if needed and tolerated).

If administered with AEDs that induce CYP enzymes (or other strong CYP inducers), an increased dose may be required (not to exceed 12 mg/day).

If hepatic impairment is evident, the daily dose should not exceed 6 mg/day or 4 mg/day for mild or moderate hepatic insufficiency, respectively. Perampanel is not recommended for use with severe hepatic or renal impairment or with hemodialysis.


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