Perampanel is available by the brand name of "Fycompa" - developed by Eisai Co. It is used in the treatment of partial and generalized seizures.

Indications of Perampanel:

• Partial-onset seizures:

  • It is indicated for the treatment of partial-onset seizures with or without secondarily generalized seizures as adjunct or single agent in patients with epilepsy who are ≥4 years of age.

• Primary generalized tonic-clonic seizures:

  • It is prescribed for the treatment of primary generalized tonic-clonic seizures as adjunct therapy in patients with epilepsy who are ≥12 years of age.

Perampanel (Fycompa) dose in adults:

Note:

Dose reduction is required in serious psychiatric or behavioral reactions and should be stopped with severe or worsening symptoms. Tablets and oral suspension may be used interchangeably.

Perampanel (Fycompa) dose in the treatment of Partial-onset seizures:

• Patients not receiving enzyme-inducing AED regimens:

  • Initial: 2 mg per oral once daily at bedtime;
  • The dose may be increased daily dose by 2 mg once daily no more frequently than at weekly intervals based on response and tolerability.

  • Recommended maintenance dose:

    • 8 to 12 mg once daily at bedtime; some patients may respond to 4 mg once daily;
    • 12 mg once daily has resulted in somewhat greater reductions in seizure rates in some patients but with a substantial increase in side effects.

• Patients receiving enzyme-inducing AED regimens (eg, phenytoin, carbamazepine, oxcarbazepine):

  • Initial: 4 mg per oral once daily at bedtime;
  • The dose may be increased daily dose by 2 mg once daily no more frequently than at weekly intervals based on response and tolerability.
  • Maintenance dose has not been established;
  • The highest dose used in clinical trials was 12 mg once daily.

Perampanel (Fycompa) dose in the treatment of primary generalized tonic-clonic seizures (adjunct): 

• Patients not receiving enzyme-inducing AED regimens:

  • Initial: 2 mg per oral once daily at bedtime;
  • The dose may be increased dose by 2 mg once daily no more frequently than at weekly intervals based on response and tolerability.

  • Recommended maintenance dose:

    • 8 mg once daily at bedtime; if tolerated and further seizure control is needed, may increase up to 12 mg once daily .
    • The maximum dose: 12 mg once daily.

• Patients receiving enzyme-inducing AED regimens (eg, phenytoin, carbamazepine, oxcarbazepine):

  • Initial 4 mg per oral once daily at bedtime;
  • The dose may be increased daily dose by 2 mg once daily no more frequently than at weekly intervals based on response and tolerability.
  • Maintenance dose has not been established; highest dose used in clinical trials was 12 mg once daily.

Perampanel (Fycompa) dose in children:

Note:

Dosing should be individualized based upon response and tolerability.

Perampanel (Fycompa) dose in the treatment of Partial seizures (adjunct or monotherapy):

• Children ≥4 years and Adolescents:

  • Patients not receiving moderate or strong CYP3A4 inducers:

    • Initial: 2 mg per oral once daily at bedtime;
    • The dose may be increased daily dose by 2 mg increments no more frequently than at weekly intervals.
    • The recommended maintenance dose range:
      • 8 to 12 mg once daily at bedtime; some patients may respond to doses of 4 mg/day.
      • Although 12 mg doses showed somewhat greater efficacy (reduction in seizure rate) in some patients, the 12 mg dose was associated with substantially higher adverse effects.
    • The maximum daily dose: 12 mg/day.

  • Patients receiving moderate or strong CYP3A4 inducers (eg, phenytoin, carbamazepine, oxcarbazepine):

    • Initial: 4 mg once daily at bedtime;
    • The dose may be increased daily dose by 2 mg increments no more frequently than at weekly intervals;
    • The target maintenance dose range not established.
    • The maximum reported dose is 12 mg/day.
    • Monitor patients closely for response and tolerability when inducer is being introduced or withdrawn from therapeutic regimen; perampanel dosing adjustment may be necessary.

Perampanel (Fycompa) dose in the treatment of primary generalized tonic-clonic seizures (adjunct):

• Children ≥12 years and Adolescents:

  • Patients not receiving moderate or strong CYP3A4 inducers:

    • Initial: 2 mg per oral once daily at bedtime;
    • The dose may be increased by 2 mg once daily no more frequently than at weekly intervals based on response and tolerability.
    • The recommended maintenance dose:
      • 8 mg once daily at bedtime; some patients may require 12 mg once daily at bedtime for further seizure control and if tolerated. maximum daily dose: 12 mg/day.

  • Patients receiving moderate or strong CYP3A4 inducers (eg, phenytoin, carbamazepine, oxcarbazepine):

    • Initial: 4 mg per oral once daily at bedtime; may increase daily dose by 2 mg once daily no more frequently than at weekly intervals; individualize dose based on response and tolerability.
    • The maximum reported dose was 12 mg/day.
    • Monitor patients closely for response and tolerability when inducer is being introduced or withdrawn from therapeutic regimen; perampanel dosing adjustment may be necessary.

Pregnancy Risk Category: C

• Studies on animal reproduction showed adverse effects at doses that were equivalent to human doses (based upon BSA).
• Perampanel therapy is not recommended for non-hormonal contraception.
• This recommendation applies to the first month of therapy. However, levonorgestrel contraception may prove less effective.

Use of Perampanel during lactation

• It is not known if breast milk contains perampanel.
• Perampanel should not be administered to nursing women unless it is indicated by the manufacturer.

Perampanel (Fycompa) dose adjustment in renal disease:

• CrCl ≥50 mL/minute:

  • No dosage adjustment necessary.

• CrCl 30 to 49 mL/minute:

  • No dosage adjustment necessary; monitor closely and consider slower titration based on response and tolerability.

• CrCl <30 mL/minute:

  • Use not recommended.

• Hemodialysis:

  • Use not recommended.

Perampanel (Fycompa) dose adjustment in liver disease:

• Mild impairment (Child Puugh class A)

  • Initial dose of 2 mg daily. May increase daily dose by 2 mg daily if needed.
  • Maximum 6 mg daily

• Moderate impairment (Child Puugh class B)

  • Initial dose of 2 mg daily. May increase daily dose by 2 mg daily if needed.
  • Maximum 4 mg daily

• Severe impairment (Child Puugh class C).

  • Not recommended.

Side effects of Perampanel (Fycompa):

• Cardiovascular:

  • Peripheral Edema

• Central Nervous System:

  • Dizziness
  • Vertigo
  • Hostility
  • Aggressive Behavior
  • Drowsiness
  • Abnormal gait
  • Fatigue
  • Headache
  • Irritability
  • Falling
  • Ataxia
  • Equilibrium Disturbance
  • Anxiety
  • Dysarthria
  • Hypoesthesia
  • Hypersomnia
  • Anger
  • Memory Impaired
  • Paresthesia
  • Confusion
  • Euphoria
  • Mood Changes
  • Agitation
  • Altered Mental Status
  • Delusion
  • Disorientation
  • Emotional Lability
  • Homicidal Ideation
  • Paranoia
  • Psychiatric Disturbance

• Dermatologic:

  • Skin Rash

• Endocrine & Metabolic:

  • Weight Gain
  • Hyponatremia

• Gastrointestinal:

  • Vomiting
  • Nausea
  • Abdominal Pain
  • Constipation

• Genitourinary:

  • Urinary Tract Infection

• Hematologic & Oncologic:

  • Bruise

• Neuromuscular & Skeletal:

  • Back Pain
  • Sprain
  • Myalgia
  • Arthralgia
  • Limb Pain
  • Musculoskeletal Pain
  • Weakness

• Ophthalmic:

  • Blurred Vision
  • Diplopia

• Respiratory:

  • Cough
  • Upper Respiratory Tract Infection
  • Oropharyngeal Pain

• Miscellaneous:

  • Head Trauma
  • Laceration
  • Limb Injury

Contraindications to Perampanel (Fycompa):

The US labeling of the manufacturer does not list any contraindications. Canadian labeling

• Hypersensitivity to perampanel and any other component of the formulation

Warnings and precautions

• CNS effects

  • The effects of therapy can include fatigue, dizziness, gait disorders (including ataxia, abnormal coordination, and balance disorder), as well as somnolence.

• Multiorgan hypersensitivity reactions

  • Fatal drug reaction presenting as eosinophilia or systemic symptoms (DRESS), accompanied by fever, rash and lymphadenopathy.
  • You should look out for signs and symptoms that indicate organ involvement.
  • Although lymphadenopathy and fever can develop early, it is possible to avoid rash by switching to other agents.

• Neuropsychiatric disorders [US Boxed Warning]

  • Therapy can lead to life-threatening neuropsychiatric events like aggression, anger and homicidal ideas and threats, hostility and irritability.
  • Patients with a history of aggression, psychiatric disorders, or a combination of drugs associated with aggression and hostility will need to be closely monitored.
  • If you have persistent, severe or worsening mental symptoms, it is important to stop therapy immediately.
  • It is important to avoid concurrent alcohol consumption as it can lead to a worsening of moods and anger.

• Suicidal thoughts:

  • Anti epileptics increase the risk of suicidal behavior/thoughts.
  • Suicidal thoughts and depression can be detected by monitoring behavior changes.

• Hepatic impairment

  • Patients with severe impairment should not use this medication. For mild to moderate hepatic impairment, dosage adjustments are recommended.

• Renal impairment

  • Patients with severe impairments or on hemodialysis should not use this product.

Perampanel: Drug Interaction

Monitoring parameters:

• Weight
• Seizure frequency/duration
• Suicidal thoughts, depression, behavioral changes during therapy and for at least 1 month after discontinuation.

How to administer Perampanel (Fycompa)?

Tablets

• Do not eat at bedtime.

Oral suspension

• Before each administration, shake well. 
• To measure the dose, a calibrated measuring device is required.
• Before you use the adapter, insert it into the neck of your bottle.
• The adapter should stay in place for as long as possible.
• The adapter should be inserted with the dosing needle.
• Once the adapter is in place, the dose can be taken from the inverted glass. 
• After each use, the cap must be replaced and properly fitted.

Mechanism of action of Perampanel (Fycompa):

• It is unclear what mechanism perampanel uses to exert anti-seizure power.
• It is an antagonist noncompetitive to the ionotropic alpha–amino-3–hydroxy-5–methyl-4–isoxazolepropionic Acid (AMPA) glutamate receiver on postsynaptic neuronal neurons.
• Glutamate is the primary excitatory neurotransmitter of the central nervous system. It causes neuronal overload, leading to many neurological disorders.

Notice:

• Pediatric patients aged >=4 years are subject to the same pharmacokinetic data as adults.

Absorption:

• Complete and rapid; fast food slows down the rate of absorption

Protein binding

• 95% to 96%, primarily albumin and alpha-acid glycoprotein 1.

Metabolism:

• Extensive via primary oxidation mediated CYP3A4/5 and to a lesser degree by CYP1A2 or CYP2B6, as well as sequential glucuronidation

Half-life elimination:

• 105 hours

Time to peak:

• 0.5 to 2.5 hours; delayed 1 to 3 hours with food

Excretion:

• Tablet: Feces (48%); urine (22%)

International Brands of Perampanel:

• Fycompa
• Glutablock
• Panelitic
• Perampalepsy

Perampanel Brand Names in Pakistan:

No Brands Available in Pakistan.