Perampanel is a selective non-competitive AMPA receptor antagonist approved as an adjunctive therapy for focal seizures. It has rapid absorption and is extensively metabolized, with potential for drug interactions. Common side effects include dizziness and somnolence. Special populations like the elderly, adolescents, pregnant women, and those with hepatic or renal impairment require modified dosing or caution. Careful titration and monitoring is important when initiating perampanel treatment.

1. Perampanel
for
Focal Epilepsy
Ade Wijaya, MD – November 2019

2. Rudzinski LA, Vélez-Ruiz NJ, Gedzelman ER, Mauricio EA, Shih JJ, Karakis I. New antiepileptic drugs: focus on ezogabine, clobazam, and perampanel. Journal of Investigative Medicine. 2016 Aug 1;64(6):1087-101.

3. Perampanel
• A selective non-competitive AMPA (a-amino-3-hydroxy-5-methyl-4-
isoxazolepropionic acid) receptor antagonist
• Adjunctive therapy for focal seizures with or without secondarily
generalized seizures in patients >12 years with epilepsy
• Initial dose: 2 mg/day can be titrated to optimal dose with maxium dose 12
mg/day
• Once daily
Trinka E, Steinhoff BJ, Nikanorova M, Brodie MJ. Perampanel for focal epilepsy: insights from early clinical experience. Acta Neurologica Scandinavica. 2016 Mar;133(3):160-72.

4. Pharmacokinetics
• Rapid and complete absorption with negligible first-pass metabolism.
• The median time to reach peak concentration varies between 0.5 to 2.5 hours
fasting (delayed by two to three hours when taken with food).
• Peak plasma concentration is reached in approximately one hour (decreased
by 40% when taken with food).
• It is worth noting that the extent of absorption is not affected by food
Fycompa (perampanel) prescribing information. Woodcliff Lake, New Jersey: Eisai R&D Management (Eisai Ltd.); 2016.
Franco V, Crema F, Iudice A, et al. Novel treatment options for epilepsy: focus on perampanel.Pharmacol Res. 2013;70(1):35–40.

5. Pharmacokinetics
• 95% to 96% protein-bound in the concentration range of 20 ng/mL to 2,000 ng/mL
• Mediated by cytochrome P450 (CYP) 3A4/5, CYP1A2, and CYP2B6, perampanel is
metabolized extensively through oxidation followed by glucuronidation
• Approximately 30% and 70% of oxidative and conjugated metabolites being
found in urine and feces, respectively
Fycompa (perampanel) prescribing information. Woodcliff Lake, New Jersey: Eisai R&D Management (Eisai Ltd.); 2016.
Franco V, Crema F, Iudice A, et al. Novel treatment options for epilepsy: focus on perampanel.Pharmacol Res. 2013;70(1):35–40.

6. Pregnancy and Lactation
• pregnancy category C, indicating it may cause fetal harm based on animal
studies; however, due to the lack of well-controlled studies in pregnant
women, the risk is uncertain.
• Administration of perampanel during organogenesis in rats and rabbits
resulted in diverticulum of the intestine, reduced fetal body weight, and
embryo lethality
• Caution is advised when considering the use of perampanel in women who
are of child-bearing age or who may be pregnant or nursing
Fycompa (perampanel) prescribing information. Woodcliff Lake, New Jersey: Eisai R&D Management (Eisai Ltd.); 2016.
Fycompa (perampanel) product monograph. Mississauga, Ontario: Eisai Ltd; 2013

7. Adverse Effects
• Dizziness (10.0–47.9%) and somnolence (9.3–18.2%)] and were dose
dependent.
• Headache, fall, irritability, ataxia, and fatigue also occurred in ≥10% of
patients in any treatment group.
• Aggression, ataxia, blurred vision, convulsion, dizziness, dysarthria, fatigue,
headache, hypersomnia, somnolence, and vertigo most frequently resulted in
the discontinuation, reduction, or interruption of perampanel dosing
Krauss GL, perucca E, ben-Menachem E, et al. Longterm safety of perampanel and seizure outcomes in refractory partial-onset seizures and secondarily generalized seizures: results from phase III extension study 307. Epilepsia 2014;55:1058–68.

8. Perampanel and The Elderly
• The efficacy and tolerability in elderly patients was good
• Slowet titration rate (less than 2 mg per 2 weeks)
Trinka E, Steinhoff BJ, Nikanorova M, Brodie MJ. Perampanel for focal epilepsy: insights from early clinical experience. Acta Neurologica Scandinavica. 2016 Mar;133(3):160-72.

9. Perampanel and The Adolescents
• Behavioral problems
• Slower titration rate (every 3 or 4 weeks)
Trinka E, Steinhoff BJ, Nikanorova M, Brodie MJ. Perampanel for focal epilepsy: insights from early clinical experience. Acta Neurologica Scandinavica. 2016 Mar;133(3):160-72.

10. Drug Interactions
• Enzyme-inducing antiepileptic agents such as carbamazepine,
oxcarbazepine, and phenytoin – increased perampanel clearance leading to a
reduction of serum levels of up to 30%
• The concomitant use of central nervous system depressants such as alcohol,
benzodiazepines, narcotics, barbiturates, and sedating antihistamines may
cause additive central nervous system depression
• Perampanel can reduce levonorgestrel serum levels by 40%, thus rendering
contraceptives containing levonorgestrel less effective.
LAURENZA A, FERRY J, HUSSEIN Z. Population pharmacokinetics and pharmacodynamics of perampanel: a pooled analysis of three phase III trials. Epilepsy Curr 2012;12(Suppl 1):216–7
Fycompa (perampanel) prescribing information. Woodcliff Lake, New Jersey: Eisai R&D Management (Eisai Ltd.); 2016.
Fycompa (perampanel) product monograph. Mississauga, Ontario: Eisai Ltd; 2013

11. Dose Modifications
• Coadministration with enzyme inducing antiepileptic drugs: initial dose 4
mg / day oncrease by 2 mg in weekly interval
• Hepatic impairment: mild (maximum 6 mg/day), moderate (maximum 4
mg/day), severe (not recommended)
• Not recommended for patients with severe renal impairmen or hemodialysis
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12. Summary
• Safe and effective adjunctive treatment option for patients with focal epilepsy
• The most frequently reported adverse events are dizziness, fatigue, and
somnolence
• Careful monitoring of the patient’s clinical status, concomitant medications,
and comorbid conditions is essential when initiating and titrating
perampanel

13. THANK YOU