Perampanel – Fycompa R
Partial Onset Seizures
Indicated as adjunctive therapy for treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy
In absence of enzyme-inducing AEDs: 2 mg PO qHS initially; increase by 2 mg/day increments in at least weekly intervals to 4-8 mg qHS
Dosage range: 8-12 mg/day
Dosing Modifications
Hepatic impairment
- Mild-to-moderate: 2 mg PO qHS initially; increase by 2 mg/day increments no more frequently than q2weeks to target dose
- Mild (maximum dose): Not to exceed 6 mg/day
- Moderate (maximum dose): Not to exceed 4 mg/day
- Severe: Not recommended
Renal impairment
- Moderate: May be used with close monitoring and slower titration
- Severe or hemodialysis: Not recommended
Pharmacology
Mechanism of Action
Noncompetitive antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor on post-synaptic neurons; glutamate is a primary excitatory neurotransmitter in the CNS and is implicated in various neurological disorders caused by neuronal over excitation
Absorption
Rapid and complete absorption
Peak Plasma Time: 0.5-2.5 hr (fasting)
Food does not affect extent of absorption, but slows rate of absorption; Cmax decreased by 28-40% and Tmax delayed by 2-3 hr compared to fasted conditions
Distribution
Protein Bound: 95-96% (mainly albumin and alfa1-acid glycoprotein)
Metabolism
Extensively metabolized in liver via primary oxidation and sequential glucuronidation
Oxidative metabolism mediated by CYP3A4 and/or CYP3A5
Elimination
Half-life: 105 hr
Renal clearance: 12 mL/min
Excretion: Feces (48%); urine (22%)
Adverse Effects
>10%
Dizziness (16-43%)
Somnolence (9-18%)
Headache (11-13%)
Fatigue (8-12%)
Irritability (4-12%)
1-10%
Falls (2-10%)
Nausea (6-8%)
Ataxia (1-8%)
Vertigo (3-5%)
Balance disorder (3-5%)
Back pain (2-5%)
Weight gain (4%)
Vomiting (2-4%)
Anxiety (3-4%)
Blurred vision (1-4%)
Dysarthria (1-4%)
Cough (1-4%)
Hypoaesthesia (3%)
Constipation (2-3%)
Arthralgia (2-3%)
Extremity pain (2-3%)
Aggression (1-3%)
Anger (1-3%)
Myalgia (1-3%)
Diplopia (1-3%)
Injuries due to falls (1-3%)
Hypersomnia (1-3%)
Hyponatremia (2%)
Contusions (2%)
Oropharyngeal pain (2%)
Asthenia (1-2%)
Confusional state (1-2%)
Euphoric mood (1-2%)
Altered mood (1-2%)
Abnormal coordination (1-2%)
Musculoskeletal pain (1-2%)
Peripheral edema (1-2%)
Memory impairment (1-2%)
Paraesthesia (1-2%)