title: Perampanel efficacy and tolerability with enzyme-inducing AEDs in patients with epilepsy.
abstract: 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.
  
  
  METHODS
  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.
authors: 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.
authors: Barry E
authors: BE
authors: Gidal
authors: 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.
authors: Antonio
authors: A
authors: Laurenza
authors: 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.
authors: Ziad
authors: Z
authors: Hussein
authors: 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.
authors: Haichen
authors: H
authors: Yang
authors: 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.
authors: Randi
authors: R
authors: Fain
authors: 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.
authors: Jacob
authors: J
authors: Edelstein
authors: 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.
authors: Dinesh
authors: D
authors: Kumar
authors: 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.
authors: Jim
authors: J
authors: Ferry
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects; D065701:Cytochrome P-450 CYP3A Inducers / Q000008:administration & dosage* / Q000009:adverse effects; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced / Q000175:diagnosis; D004244:Dizziness / Q000139:chemically induced / Q000175:diagnosis; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004347:Drug Interactions; D004827:Epilepsy / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D005221:Fatigue / Q000139:chemically induced / Q000175:diagnosis; D005260:Female; D006801:Humans; D038622:Internationality; D008297:Male; D001523:Mental Disorders / Q000139:chemically induced / Q000175:diagnosis; D009570:Nitriles; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D065701:Cytochrome P-450 CYP3A Inducers; D004338:Drug Combinations; D009570:Nitriles; D011728:Pyridones; C551441:perampanel