Dosing and uses of Fycompa (perampanel)
Adult dosage forms and strengths
tablet: Schedule III
- 2mg
- 4mg
- 6mg
- 8mg
- 10mg
- 12mg
oral suspension
- 0.5mg/mL
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
Tonic Clonic Seizures
Indicated as adjunctive therapy for the treatment of primary generalized tonic-clonic 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 recommended maintenance dose of 8 mg qHs
If 8 mg/day is well tolerated but further control is needed, may increase up to 12 mg/day
Dosage modifications
Enzyme inducing antiepileptic drugs (AEDs): Coadministration with enzyme inducing AEDs (eg, phenytoin, carbamazepine, oxcarbazepine, phenobarbital, primidone, topiramate): 4 mg PO qHS initially; increase by 2 mg/day increments in at least weekly intervals up to 8-12 mg/day
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
Pediatric dosage forms and strengths
tablet: Schedule III
- 2mg
- 4mg
- 6mg
- 8mg
- 10mg
- 12mg
oral suspension
- 0.5mg/mL
Partial Onset Seizures
Indicated as adjunctive therapy for treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy
<12 years: Safety and efficacy not established
In absence of enzyme-inducing AEDs ≥12 years: 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
Tonic Clonic Seizures
Indicated as adjunctive therapy for the treatment of primary generalized tonic-clonic seizures in patients with epilepsy
<12 years: Safety and efficacy not established
In absence of enzyme-inducing AEDs: 2 mg PO qHS initially; increase by 2 mg/day increments in at least weekly intervals to recommended maintenance dose of 8 mg qHs
If 8 mg/day is well tolerated but further control is needed, may increase up to 12 mg/day
Dosage modifications
Coadministration with enzyme inducing AEDs (eg, phenytoin, carbamazepine, oxcarbazepine, phenobarbital, primidone, topiramate): 4 mg PO qHS initially; increase by 2 mg/day increments in at least weekly intervals up to 8-12 mg/day
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
Fycompa (perampanel) adverse (side) 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%)
Warnings
Black box warnings
Serious or life-threatening psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger, and homicidal ideation, and threats reported
May occur with and without prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression
Advise patients and caregivers to contact a healthcare provider immediately if any of these reactions or changes in mood, behavior, or personality that are not typical for the patient are observed
Closely monitor patients particularly during the titration period and at higher doses
Contraindications
None
Cautions
Serious psychiatric and behavioral reactions (eg, hostility, aggression) may emerge and appear to be dose related
Antiepileptic drugs increase risk of suicidal thoughts or behavior; monitor for emergence or worsening of depression, suicidal thoughts or behavior, and unusual mood/behavior changes
Dizziness, vertigo, and gait disturbances reported
Somnolence and fatigue reported; caution patients against engaging in hazardous activities that require mental alertness
Increased risk of falls
CYP inducers (eg, carbamazepine, oxcarbazepine, phenytoin, phenobarbital, primidone, topiramate) may greatly increase clearance, resulting in reduced perampanel plasma concentrations (see Dosage modifications)
Additive CNS depression likely when coadministered with alcohol or other CNS depressants
Pregnancy and lactation
Pregnancy category: C; Administration to pregnant rats throughout organogenesis resulted in an increase in visceral abnormalities
North American Antiepileptic Drug (NAAED) Pregnancy Registry: 1-888-233-2334
Lactation: Unknown whether distributed in human breast milk; caution advised
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Fycompa (perampanel)
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
Bioavailability: Oral suspension has comparable bioavailability to tablets under steady state; both formulations may be used interchangeably
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%)
Administration
Oral Administration
May take tablet or oral suspension with or without food
Tablet and oral suspension may be used interchangeably on a mg-per-mg basis
Oral suspension
- Shake well before measuring dose for each administrations
- Use provided adapter and graduated oral dosing syringe to accurately administer the oral suspension; household teaspoons or tablespoons are not an adequate measuring device
- The adapter, which is supplied in the product carton, should be inserted firmly into the neck of the bottle before use and remain in place for the duration of the usage of the bottle
- The dosing syringe should be inserted into the adapter and the dose withdrawn from the inverted bottle
- The cap should be replaced after each use; the cap fits properly when the adapter is in place
