Perampanel efficacy and tolerability with enzyme-inducing AEDs in patients with
epilepsy.
Author(s): Gidal BE(1), Laurenza A(2), Hussein Z(2), Yang H(2), Fain R(2), Edelstein J(2),
Kumar D(2), Ferry J(2).
Affiliation(s): Author information:
(1)From the School of Pharmacy (B.E.G.), University of Wisconsin, Madison; Eisai
Neuroscience Product Creation Unit (A.L., J.F., H.Y., D.K.), Woodcliff Lake, NJ;
Eisai Ltd. (Z.H.), Hatfield, UK; Eisai Medical and Scientific Affairs (R.F.),
Woodcliff Lake, NJ; and formerly of Sui Generis Health (J.E.), New York, NY.
barry.gidal@wisc.edu. (2)From the School of Pharmacy (B.E.G.), University of
Wisconsin, Madison; Eisai Neuroscience Product Creation Unit (A.L., J.F., H.Y.,
D.K.), Woodcliff Lake, NJ; Eisai Ltd. (Z.H.), Hatfield, UK; Eisai Medical and
Scientific Affairs (R.F.), Woodcliff Lake, NJ; and formerly of Sui Generis Health
(J.E.), New York, NY.
Publication date & source: 2015, Neurology. , 84(19):1972-80
OBJECTIVE: Evaluate the impact of concomitant enzyme (CYP3A4)-inducer
antiepileptic drugs (EIAEDs) on the efficacy and safety of perampanel in patients
from the 3 phase-III clinical trials.
METHODS: Patients with pharmacoresistant partial-onset seizures in the 3
phase-III clinical studies were aged 12 years and older and receiving 1 to 3
concomitant antiepileptic drugs. Following 6-week baseline, patients were
randomized to once-daily, double-blind treatment with placebo or perampanel 8 or
12 mg (studies 304 and 305) or placebo or perampanel 2, 4, or 8 mg (study 306).
RESULTS: Treatment response assessed by median percent reduction in seizure
frequency and responder rates improved with perampanel compared with placebo.
However, at 8 and 12 mg, the treatment response was significantly greater in
patients receiving non-EIAEDs. The treatment effect (perampanel-placebo) also
demonstrated a dose-dependent increase in all patients. The overall incidence of
treatment-emergent adverse events was similar regardless of the presence of
EIAEDs. Occurrence of some adverse events, such as fatigue, somnolence,
dizziness, irritability, was greater in patients receiving non-EIAEDs, as was
discontinuation because of adverse events.
CONCLUSIONS: Perampanel shows efficacy and safety in the presence and absence of
EIAEDs. As systemic exposure to perampanel increases, so does efficacy. Given the
extensive metabolism of perampanel, systemic exposure is clearly reduced with
concomitant administration of CYP3A4 inducers. This supports the strategy of
dosing perampanel to clinical effect. Recognition of these pharmacokinetic
interactions will be important in the optimization of this novel medication.
CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that 2 to 12
mg/d doses of perampanel reduced seizure frequency and improved responder rate in
the presence and absence of EIAEDs.
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