perampanel (Rx)

Brand and Other Names:Fycompa
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet: Schedule III

  • 2mg
  • 4mg
  • 6mg
  • 8mg
  • 10mg
  • 12mg

oral suspension

  • 0.5mg/mL

Partial Onset Seizures

Initial

  • In absence of concomitant enzyme-inducing antiepileptic drugs (AEDs): 2 mg PO qHS initially; increase by 2 mg/day increments in at least weekly intervals based on clinical response and tolerability to 4-8 mg qHS

Maintenance

  • Dosage range: 8-12 mg/day
  • Response may occur with 4 mg/day; 12 mg/day resulted in greater seizure rate reductions and greater substantial increase in side effects

Tonic Clonic Seizures

Indicated as adjunctive therapy for primary generalized tonic-clonic seizures in patients with epilepsy

Initial

  • In absence of enzyme-inducing AEDs: 2 mg PO qHS initially; increase by 2 mg/day increments in at least weekly intervals based on clinical response and tolerability

Maintenance

  • 8 mg PO 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
  • Maintenance dose has not been studied or established

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

Geriatric Dosing

  • ≥65 years: Increase dosage no more frequently than q2weeks to target dose

Dosing considerations

Psychiatric or behavioral adverse events (eg, aggression, hostility, irritability, anger) occurs reduce dosage; discontinue immediately if symptoms are severe or worsening

Dosage Forms & Strengths

tablet: Schedule III

  • 2mg
  • 4mg
  • 6mg
  • 8mg
  • 10mg
  • 12mg

oral suspension

  • 0.5mg/mL

Partial Onset Seizures

Indicated as monotherapy or adjunctive therapy for partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy

<12 years: Safety and efficacy not established

≥12 years

  • Initial
    • In absence of enzyme-inducing AEDs: 2 mg PO qHS; increase by 2 mg/day increments in at least weekly intervals to 4-8 mg qHS based on clinical response and tolerability
  • Maintenance
    • Dosage range: 8-12 mg/day
    • Response may occur with 4mg/day; 12 mg/day resulted in greater seizure rate reductions and greater substantial increase in side effects

Tonic Clonic Seizures

Indicated as adjunctive therapy of primary generalized tonic-clonic seizures in patients with epilepsy

<12 years: Safety and efficacy not established

≥12 years

  • Initial
    • In absence of enzyme-inducing AEDs: 2 mg PO qHS initially; increase by 2 mg/day increments in at least weekly intervals based on clinical response and tolerability
  • Maintenance
    • 8 mg PO qHS
    • If 8 mg/day is well tolerated but further seizure 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
  • Maintenance dose has not been studied or established

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
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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%)

Postmarketing Reports

Acute psychosis, hallucinations, delusions, paranoia, delirium, disorientation

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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

Reduce dose if psychiatric and behavioral reactions occur and discontinue if symptoms are severe or worsen

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; monitor

Somnolence and fatigue reported; caution patients against engaging in hazardous activities that require mental alertness

Increased risk of falls

Reports of drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity; presents with hypersensitivity reactions (eg, lymphadenopathy, fever, rash, and/or facial swelling) in association with other systemic organ involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis); monitor early manifestations of hypersensitivity; discontinue therapy if alternative etiology is not established

Moderate to strong CYP3A4 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

Abrupt withdrawal should be avoided unless in response to adverse event; increased risk of seizure frequency

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Pregnancy & Lactation

Pregnancy

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs); encourage women to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org

There are no adequate data on the developmental risk associated with use in pregnant women; in animal studies, perampanel induced developmental toxicity in pregnant rat and rabbit at clinically relevant doses

Contraception

  • Advise women who are using a levonorgestrel-containing contraceptive to use an additional non-hormonal form (eg, condoms) of contraception while in therapy and for a month after discontinuation

Lactation

Perampanel and/or its metabolites are present in rat milk, and are detected at concentrations higher than that in maternal plasma

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed child from therapy or from the underlying maternal condition

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.

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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

The mechanism for its antiepileptic effects in humans is still unknown

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 11-40% and Tmax delayed by 1-3 hr compared to fasted conditions

Distribution

Protein Bound: 95-96% (mainly albumin and alfa1-acid glycoprotein)

Blood to plasma ratio: 0.55-0.59

Metabolism

Extensively metabolized in liver via primary oxidation and sequential glucuronidation

In vitro studies indicated, oxidative metabolism mediated mainly by CYP3A4 and/or CYP3A5; lesser extent by CYP1A2 and CYP2B6

Elimination

Half-life: 105 hr

Renal clearance: 12 mL/min

Excretion: Feces (48%); urine (22%)

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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
  • Discard any unused oral suspension remaing 90 days after first opening the bottle

Storage

Tablet

  • Store at room temperature: 68 - 77°F (20- 25°C); excursions permitted to 59-86°F (15-30°C)

Oral Suspension

  • Do not store above 86°F (30°C). Do not freeze. Use within 90 days after the first opening of the bottle.
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Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
  • Manage and view all your plans together – even plans in different states.
  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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