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Perampanel

Class: Anticonvulsants, Miscellaneous
VA Class: CN400
Chemical Name: 2 - (1′,6′ - Dihydro - 6′ - oxo - 1′ - phenyl[2,3′ - bipyridin] - 5′ - yl) - benzonitrile
Molecular Formula: C23H15N3O
CAS Number: 380917-97-5
Brands: Fycompa

Warning(s)

  • Serious Psychiatric and Behavioral Reactions
  • Risk of serious, potentially life-threatening, psychiatric and behavioral reactions (e.g., aggression, hostility, irritability, anger, homicidal ideation and threats).1 5 6 8 20 (See Serious Psychiatric and Behavioral Reactions under Cautions.)

  • Reactions have occurred in patients with and without underlying risk factors (e.g., prior psychiatric history, concomitant use of other drugs known to cause hostility and aggression).1 8

  • Monitor patients for adverse psychiatric effects, particularly during initial dosage titration, subsequent dosage increases, and when higher dosages of the drug are used.1

  • Reduce dosage if any such manifestations occur; permanently discontinue drug if symptoms are severe or worsen.1

Introduction

Anticonvulsant; a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor antagonist.1 2 3 4 14 15 16 19 22 23

Uses for Perampanel

Seizure Disorders

Management (in combination with other anticonvulsants) of partial-onset seizures in patients ≥12 years of age with epilepsy.1 2 3 4 5 6 17 23

Management (in combination with other anticonvulsants) of primary generalized tonic-clonic seizures in patients ≥12 years of age with epilepsy.1

Designated an orphan drug by FDA for treatment of Lennox-Gastaut syndrome; not FDA-labeled for this orphan indication.24

Perampanel Dosage and Administration

General

  • When discontinuing anticonvulsant therapy, gradual withdrawal is recommended to minimize potential for increased seizure frequency.1 (See Discontinuance of Anticonvulsants under Cautions.)

  • Closely monitor for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.1 10 11 12 (See Suicidality Risk under Cautions.)

Administration

Oral Administration

Administer orally once daily at bedtime; may be given without regard to food.1 25 (See Absorption under Pharmacokinetics.)

Dosage

Initial dosage recommendations vary based on whether a CYP enzyme-inducing anticonvulsant agent (e.g., carbamazepine, oxcarbazepine, phenytoin) is administered concomitantly.1 6 Such CYP-inducing anticonvulsants can reduce plasma concentrations and thus efficacy of perampanel.1 6 8 (See Interactions.)

Monitor for adverse neuropsychiatric effects, particularly during initial titration period (or any other time dosage is increased) and when high dosages (e.g., 12 mg daily) are used.1 If neuropsychiatric manifestations occur, reduce dosage of perampanel or discontinue therapy depending on severity of the reaction.1 (See Serious Psychiatric and Behavioral Reactions under Cautions.)

Pediatric Patients

Seizure Disorders
Partial Seizures
Oral

Children ≥12 years of age not concomitantly receiving a CYP-inducing anticonvulsant: Initially, 2 mg once daily.1 Increase dosage by increments of 2 mg daily no more frequently than once a week up to the recommended dosage range of 4–12 mg once daily; individualize dosage based on clinical response and tolerability.1

Children ≥12 years of age concomitantly receiving a CYP-inducing anticonvulsant: Initially, 4 mg once daily.1 Increase dosage by increments of 2 mg daily no more frequently than once a week up to the recommended dosage range of 4–12 mg once daily; individualize dosage based on clinical response and tolerability.1

In principal efficacy studies, a dosage of 12 mg daily provided little additional benefit over 8 mg daily and was associated with an increased incidence of adverse effects (e.g., neuropsychiatric effects).2 3 6 15 In general, increase dosage to 12 mg daily only if tolerated and clinically indicated.2 3 6 15

Dosage adjustment may be necessary when CYP-inducing anticonvulsants are added to, or discontinued from, a patient's anticonvulsant regimen; closely monitor for clinical response and tolerability in such cases.1 (See Interactions.)

Primary Generalized Tonic-Clonic Seizures
Oral

Children ≥12 years of age not concomitantly receiving a CYP-inducing anticonvulsant: Initially, 2 mg once daily.1 Increase dosage by increments of 2 mg daily no more frequently than once a week up to a dosage of 8 mg once daily.1 Patients tolerating a dosage of 8 mg daily and who require further seizure control may benefit from a dosage increase to 12 mg once daily.1 Adjust dosage based on clinical response and tolerability.1

Children ≥12 years of age concomitantly receiving a CYP-inducing anticonvulsant: Initially, 4 mg once daily.1 Increase dosage by increments of 2 mg daily no more frequently than once a week up to a dosage of 12 mg once daily.1 Adjust dosage based on clinical response and tolerability.1

Dosage adjustment may be necessary when CYP-inducing anticonvulsants are added to, or discontinued from, a patient's anticonvulsant regimen; closely monitor for clinical response and tolerability in such cases.1 (See Interactions.)

Adults

Seizure Disorders
Partial Seizures
Oral

Patients not concomitantly receiving a CYP-inducing anticonvulsant: Initially, 2 mg once daily.1 Increase dosage by increments of 2 mg daily no more frequently than once a week up to the recommended dosage range of 4–12 mg once daily; individualize dosage based on clinical response and tolerability.1

Patients concomitantly receiving a CYP-inducing anticonvulsant: Initially, 4 mg once daily.1 Increase dosage by increments of 2 mg daily no more frequently than once a week up to the recommended dosage range of 4–12 mg once daily; individualize dosage based on clinical response and tolerability.1

In principal efficacy studies, a dosage of 12 mg daily provided little additional benefit over 8 mg daily and was associated with an increased incidence of adverse effects (e.g., neuropsychiatric effects).2 3 6 15 In general, increase dosage to 12 mg daily only if tolerated and clinically indicated.2 3 6 15

Dosage adjustment may be necessary when CYP-inducing anticonvulsants are added to, or discontinued from, a patient's anticonvulsant regimen; closely monitor for clinical response and tolerability in such cases.1 (See Interactions.)

Primary Generalized Tonic-Clonic Seizures
Oral

Patients not concomitantly receiving a CYP-inducing anticonvulsant: Initially, 2 mg once daily.1 Increase dosage by increments of 2 mg daily no more frequently than once a week up to a dosage of 8 mg once daily.1 Patients tolerating a dosage of 8 mg daily and who require further seizure control may benefit from a dosage increase to 12 mg once daily.1 Adjust dosage based on clinical response and tolerability.1

Patients concomitantly receiving a CYP-inducing anticonvulsant: Initially, 4 mg once daily.1 Increase dosage by increments of 2 mg daily no more frequently than once a week up to a dosage of 12 mg once daily.1 Adjust dosage based on clinical response and tolerability.1

Dosage adjustment may be necessary when CYP-inducing anticonvulsants are added to, or discontinued from, a patient's anticonvulsant regimen; closely monitor for clinical response and tolerability in such cases.1 (See Interactions.)

Prescribing Limits

Pediatric Patients

Seizure Disorders
Partial Seizures
Oral

Pediatric patients ≥12 years of age: Maximum 12 mg once daily.1

Primary Generalized Tonic-Clonic Seizures
Oral

Pediatric patients ≥12 years of age: Maximum 12 mg once daily.1

Adults

Seizure Disorders
Partial Seizures
Oral

Maximum 12 mg once daily.1

Primary Generalized Tonic-Clonic Seizures
Oral

Maximum 12 mg once daily.1

Special Populations

Hepatic Impairment

Mild hepatic impairment: Initially, 2 mg once daily; may increase by increments of 2 mg daily no more frequently than once every 2 weeks up to a maximum of 6 mg once daily.1 Individualize dosage based on patient response and tolerability.1

Moderate hepatic impairment: Initially, 2 mg once daily; may increase by increments of 2 mg daily no more frequently than once every 2 weeks up to a maximum of 4 mg once daily.1 Individualize dosage based on patient response and tolerability.1

Severe hepatic impairment: Use not recommended.1 (See Hepatic Impairment under Cautions.)

Renal Impairment

Mild renal impairment: No dosage adjustment necessary.1

Moderate renal impairment: Consider a slower titration schedule based on patient response and tolerability; monitor closely.1

Severe renal impairment and patients undergoing hemodialysis: Use not recommended.1 (See Renal Impairment under Cautions.)

Geriatric Patients

Patients ≥65 years of age: Titrate more slowly than usual, increasing dosage no more frequently than once every 2 weeks.1 (See Geriatric Use under Cautions.)

Gender or Race

Dosage adjustment not required.1

Cautions for Perampanel

Contraindications

  • None.1

Warnings/Precautions

Warnings

Serious Psychiatric and Behavioral Reactions

Serious, sometimes life-threatening, psychiatric and behavioral reactions reported.1 5 6 8 20

Adverse neuropsychiatric events include irritability, anger, agitation, anxiety, labile affect, belligerence, hostility, aggression, homicidal ideation and/or threats, and physical assaults.1 5 6 8 20 (See Boxed Warning.) Effects are dose related, generally occurring within the first 6 weeks of therapy.1 5

Some patients may experience worsening of their preexisting psychiatric condition.1

Suicidal ideation and suicide attempts also reported.2 4 6 8 26 (See Suicidality Risk under Cautions.)

Other neuropsychiatric effects such as disorientation/confusional state, delusion, paranoia, euphoric mood, and mental status changes also observed.1 6 (See Abuse Potential and Dependence under Cautions.)

Concomitant use of alcohol may substantially worsen mood and increase anger; avoid alcohol use during therapy.1 (See Specific Drugs under Interactions and also see Advice to Patients.)

Monitor for psychiatric and behavioral reactions as well as for unusual changes in mood, behavior, or personality during and for at least 1 month following discontinuance of therapy.1 (See Advice to Patients.) Monitoring is particularly important during the first few weeks of therapy (titration period), following dosage increases, and when higher dosages are used.1

If any such manifestations occur, reduce dosage; if symptoms are persistently severe or worsening, immediately and permanently discontinue perampanel and refer patient for psychiatric evaluation.1

Other Warnings and Precautions

Suicidality Risk

Increased risk of suicidality (suicidal behavior or ideation) observed in an analysis of studies using various anticonvulsants in patients with epilepsy, psychiatric disorders (e.g., bipolar disorder, depression, anxiety), and other conditions (e.g., migraine, neuropathic pain); risk in patients receiving anticonvulsants (0.43%) was approximately twice that in patients receiving placebo (0.24%).1 10 11 12 Increased suicidality risk was observed ≥1 week after initiation of anticonvulsant therapy and continued through 24 weeks.1 10 11 Risk was higher for patients with epilepsy compared with those receiving anticonvulsants for other conditions.1 10

Closely monitor all patients currently receiving or beginning anticonvulsant therapy for changes in behavior that may indicate emergence or worsening of suicidal thoughts or behavior or depression.1 10 11 12 Anxiety, agitation, hostility, hypomania, and mania may be precursors to emerging suicidality.10

Balance risk of suicidality with risk of untreated illness.1 10 Epilepsy and other illnesses treated with anticonvulsants are themselves associated with morbidity and mortality and an increased risk of suicidality.1 12 If suicidal thoughts or behavior emerges during anticonvulsant therapy, consider whether these symptoms may be related to the illness itself.1 12 (See Advice to Patients.)

Neurologic Effects

Risk of dose-related adverse neurologic effects (e.g., dizziness, vertigo, disturbances in gait or coordination, somnolence, fatigue); generally observed during dosage titration period.1 4 13 20 (See Advice to Patients.)

CNS-related events were among the most common adverse effects associated with perampanel in clinical studies;1 2 3 4 13 20 risk appears to be increased in geriatric patients and with concomitant use of alcohol and/or other CNS depressants.1 (See Geriatric Use under Cautions and also see Specific Drugs under Interactions.)

Falls and Injuries

Falls (both with and without concurrent seizures), sometimes resulting in serious injuries (e.g., head injuries, bone fractures, lacerations), reported.1 3 Falls sometimes occurred in association with other CNS-related effects (e.g., gait disturbance, ataxia, dizziness, slurred speech).3 Risk appears to be greater in geriatric patients.1 8 (See Geriatric Use under Cautions.)

Discontinuance of Anticonvulsants

Abrupt withdrawal of anticonvulsants may increase seizure frequency in patients with seizure disorders.1 In general, gradual withdrawal is recommended whenever any anticonvulsant agent is discontinued.1 However, manufacturer states that insufficient data are available to make specific recommendations regarding withdrawing perampanel.1 Because of its prolonged half-life (approximately 105 hours), plasma concentrations are expected to decline gradually even after abrupt discontinuance.1 If discontinuance of perampanel is necessary because of adverse effects, may consider prompt withdrawal of the drug.1

Abuse Potential and Dependence

Subject to control as a schedule III (C-III) drug.1 7 Abuse potential may result in moderate to low physical dependence or high psychological dependence.7

Potential to produce withdrawal symptoms not adequately evaluated to date.1 (See Discontinuance of Anticonvulsants under Cautions.)

Specific Populations

Pregnancy

Category C.1

North American Antiepileptic Drug (NAAED) Pregnancy Registry (for patients) at 888-233-2334 or .1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Caution advised when used in nursing women.1

Pediatric Use

Safety and efficacy not established in children <12 years of age.1

In controlled studies in patients with partial-onset seizures, aggression observed more frequently in adolescents than in adults.1 (See Serious Psychiatric and Behavioral Reactions under Cautions.)

No evidence of an overall negative effect on cognitive function in a short-term controlled study in adolescent patients.1

Geriatric Use

Insufficient experience in patients ≥65 years of age to establish efficacy and safety in this population.1

Because of a greater likelihood of adverse effects (e.g., dizziness, gait disturbances, falls, somnolence, fatigue), titrate dosage gradually in patients ≥65 years of age.1 (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Systemic exposure and half-life of perampanel are increased in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment; dosage adjustments recommended.1 (See Hepatic Impairment under Dosage and Administration and also see Pharmacokinetics.)

Not studied in patients with severe hepatic impairment; use not recommended.1

Renal Impairment

Not specifically evaluated to date in patients with renal impairment, but population pharmacokinetic analyses indicate that clearance may be reduced.1 (See Elimination: Special Populations, under Pharmacokinetics.)

Use with close monitoring in patients with moderate renal impairment; consider more gradual dosage titration.1 (See Renal Impairment under Dosage and Administration.)

Not studied in patients with severe renal impairment and in those undergoing hemodialysis; use not recommended.1

Common Adverse Effects

Partial-onset seizures: Dizziness,1 2 3 4 somnolence,1 2 3 4 fatigue,1 3 4 irritability,1 2 3 falls,1 2 3 nausea,1 3 weight gain,1 3 vertigo,1 ataxia,1 2 gait disturbance,1 4 balance disorder.1

Primary generalized tonic-clonic seizures: Dizziness,1 fatigue,1 headache,1 somnolence,1 irritability.1

Interactions for Perampanel

Principally metabolized by CYP3A4/5 and, to a lesser extent, by CYP1A2 and CYP2B6; other CYP-mediated pathways also may be involved.1

Weak inhibitor of CYP2C8 and 3A4; weak inducer of CYP2B6 and 3A4/5 in vitro.1 Does not inhibit CYP1A2, 2A6, 2C9, 2C19, 2D6, and 2E1 nor induce CYP1A2.1

Neither a substrate nor substantial inhibitor of the efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); organic anion transport proteins (OATP) 1B1 and 1B3; organic anion transporters 1, 2, 3, and 4; and organic cation transporters 1, 2, and 3.1

Weak inhibitor of UGT1A9 and 2B7; does not appear to inhibit UGT1A1, 1A4, and 1A6.1 Induces UGT1A1 and 1A4.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

CYP inducers: Potential pharmacokinetic interaction (e.g., decreased perampanel concentrations).1 When used concomitantly with CYP-inducing anticonvulsants, dosage adjustment of perampanel is necessary.1 (See Dosage under Dosage and Administration.) Avoid use with other potent CYP3A inducers.1

CYP3A4 inhibitors: Potential pharmacokinetic interaction (e.g., increased perampanel concentrations).1

CYP3A4 substrates: Pharmacokinetic interactions possible.1

Specific Drugs

Drug

Interaction

Comments

Alcohol

Perampanel enhances impairing effects of alcohol (e.g., inability to carry out complex tasks such as driving; decreased vigilance and alertness); increased anger, confusion, and depression1

Avoid concomitant use1

Anticonvulsants, CYP-inducing (e.g., carbamazepine, oxcarbazepine, phenytoin, phenobarbital, primidone, topiramate)

Possible decreased concentrations of perampanel by up to 67%1 9

Carbamazepine: Decreased peak concentrations and AUC of perampanel by 26 and 67%, respectively; substantially decreased half-life of perampanel1

Oxcarbazepine: Decreased perampanel AUC by 48%; oxcarbazepine clearance decreased by 26%1

Phenytoin: Decreased perampanel AUC by 43%1

Phenobarbital and primidone: Perampanel AUC not substantially affected; however, modest effect on perampanel concentrations cannot be excluded1

Topiramate: Decreased perampanel AUC by approximately 19%1

Known CYP-inducing anticonvulsants (e.g., carbamazepine, oxcarbazepine, phenytoin): Increase initial perampanel dosage in presence of such anticonvulsants; subsequent perampanel dosage adjustment may be required when CYP-inducing anticonvulsants are added to or discontinued from therapy1 (see Dosage under Dosage and Administration)

Monitor patients receiving CYP-inducing anticonvulsants closely for response1

Anticonvulsants, other (e.g., clobazam, clonazepam, lamotrigine, levetiracetam, valproic acid, zonisamide)

Clobazam, lamotrigine, valproic acid: Clearance of perampanel not affected1

Clobazam, lamotrigine, valproic acid: Clearance of these anticonvulsants increased by <10%1

Clonazepam, levetiracetam, zonisamide: Clearance of either anticonvulsant not affected1

CNS depressants (e.g., benzodiazepines, opiate analgesics, barbiturates, sedating antihistamines)

Increased risk of CNS-related adverse effects1

Use concomitantly with caution1

Contraceptives, hormonal (e.g., ethinyl estradiol with levonorgestrel)

Possible reduced contraceptive efficacy1

Substantially decreased peak concentrations and systemic exposure of levonorgestrel observed with perampanel dosage of 12 mg daily, but not 4 or 8 mg daily; systemic exposure of ethinyl estradiol not affected1

Levonorgestrel-containing contraceptives (oral or implanted): Additional nonhormonal methods of contraception recommended1

Ketoconazole

Ketoconazole (potent CYP3A4 inhibitor) increased systemic exposure and half-life of perampanel by 20 and 15%, respectively1

Levodopa

No effect on levodopa concentrations and AUC1

Midazolam

Slightly decreased peak concentrations and AUC of midazolam (CYP3A4 substrate)1

Rifampin

Rifampin (potent CYP3A inducer) may substantially reduce perampanel concentrations1

Avoid concomitant use1

St. John's wort (Hypericum perforatum)

St. John's wort (potent CYP3A inducer) may substantially reduce perampanel concentrations1

Avoid concomitant use1

Perampanel Pharmacokinetics

Absorption

Bioavailability

Rapidly and completely absorbed following oral administration; peak plasma concentrations attained within approximately 0.5–2.5 hours under fasting conditions.1 19

Food

Food slows rate, but does not affect extent, of absorption.1

Special Populations

In patients with mild hepatic impairment, total (free and protein-bound) exposure increased by 50% and AUC of free (unbound) perampanel increased by 1.8-fold.1 In patients with moderate hepatic impairment, total exposure increased by 2.55-fold and AUC of free perampanel increased by 3.3-fold.1

Distribution

Extent

Blood to plasma ratio is 0.55–0.59.1

Perampanel and/or its metabolites are distributed into milk in rats at concentrations higher than those in maternal plasma; not known whether distributed into human milk.1

Plasma Protein Binding

Approximately 95–96% (mainly to albumin and α1-acid glycoprotein).1

Elimination

Metabolism

Extensively metabolized in liver, principally by oxidation followed by glucuronidation.1 In vitro, oxidative metabolism is principally mediated by CYP3A4/5 and, to a lesser extent, by CYP1A2 and CYP2B6, although other CYP-mediated pathways may be involved.1

Elimination Route

Recovered in urine (22%) and feces (48%), mainly as oxidative and conjugated metabolites, following administration of radiolabeled dose in healthy geriatric individuals.1

Half-life

Approximately 105 hours.1

Special Populations

Hepatic impairment: Half-life is prolonged by more than twofold in patients with mild or moderate hepatic impairment.1

Renal impairment: In a population pharmacokinetic analysis in patients with partial-onset seizures, mild renal impairment (Clcr 50–80 mL/minute) reduced clearance by 27%.1 In such analysis in patients with primary generalized tonic-clonic seizures, baseline Clcr did not influence clearance.1

Ethnicity: Clearance not substantially different among patients of different ethnic origins (Caucasian, Blacks, American Indians/Alaska Natives, Chinese, Japanese, other Asians).1

Gender: Clearance slightly decreased (18%) in females versus males.1

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).1

Actions

  • Exact mechanism of anticonvulsant action not fully elucidated; however, the drug inhibits AMPA-type glutamate receptors, a class of ionotropic glutamate receptors that mediate fast excitatory neurotransmission and play a role in the generation and spread of epileptic seizures.1 14 15 16 22 23

  • Selectively and noncompetitively inhibits AMPA glutamate receptors on postsynaptic neurons, thereby reducing excessive glutamatergic activity and neuronal excitation.1 5 16

  • Highly selective for AMPA glutamate receptors; little or no inhibitory effect on N-methyl-d-aspartate (NMDA) or kainate glutamate receptors.14 22

  • Demonstrates a broad spectrum of anticonvulsant activity in various animal models.16 19

Advice to Patients

  • Importance of providing patient with a copy of manufacturer's patient information (medication guide) when perampanel therapy is begun and each time the drug is dispensed.1

  • Importance of taking perampanel only as prescribed.1

  • Risk of serious psychiatric and behavioral reactions.1 Importance of advising patients and their families and caregivers of the need to monitor for the emergence of anger; aggression; hostility; unusual changes in mood, personality, or behavior; and other behavioral symptoms during therapy and for at least 1 month following discontinuance of therapy.1 Advise patients, family members, and caregivers to immediately contact the responsible clinician if such symptoms occur.1 10

  • Risk of suicidality (anticonvulsants, including perampanel, may increase risk of suicidal thoughts or actions in about 1 in 500 people).1 10 12 Importance of patients, family members, and caregivers being alert to day-to-day changes in mood, behavior, and actions and immediately informing clinician of any new or worrisome behaviors (e.g., talking or thinking about wanting to hurt oneself or end one's life, withdrawing from friends and family, becoming depressed or experiencing worsening of existing depression, becoming preoccupied with death and dying, giving away prized possessions).1 10

  • Risk of neurologic effects such as dizziness, gait disturbance, somnolence, and fatigue.1 Importance of advising patients not to drive, operate complex machinery, or engage in other hazardous activities until they have become accustomed to any such effects.1 Importance of also advising patients that concomitant use of CNS depressants (e.g., benzodiazepines, opiate analgesics, barbiturates, sedating antihistamines) can increase risk of CNS-related adverse effects; patients should limit activity until the effects of such concomitant therapy are known.1

  • Risk of potentiated CNS impairment with concurrent use of alcohol or other CNS depressants.1 Importance of advising patients to avoid alcohol during perampanel therapy.1

  • Importance of advising patients that perampanel may increase the risk of falls (particularly in elderly patients), which can cause serious injuries.1

  • Importance of informing patients that sudden discontinuance of perampanel may increase seizure frequency.1

  • Importance of advising patients that if a dose is missed, to administer the prescribed daily dose at the regularly scheduled time the following day; if more than one day of dosing is missed, patients should contact their clinician.1

  • Importance of counseling patients that perampanel is a controlled substance that can be misused or abused.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Importance of clinicians informing women about the existence of and encouraging enrollment in the pregnancy registry (see Pregnancy under Cautions).1

  • Importance of informing women that perampanel may reduce the efficacy of levonorgestrel-containing contraceptives.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., kidney disease, liver disease, depression or other psychiatric disorders, aggressive or hostile behavior, suicidality) or family history of suicidality or bipolar disorder.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule III (C-III) drug.1 7

Perampanel

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

2 mg

Fycompa (C-III)

Eisai

4 mg

Fycompa (C-III)

Eisai

6 mg

Fycompa (C-III)

Eisai

8 mg

Fycompa (C-III)

Eisai

10 mg

Fycompa (C-III)

Eisai

12 mg

Fycompa (C-III)

Eisai

AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

Date modified: November 09, 2016
Last reviewed: March 09, 2015
Date published: March 09, 2015

References

1. Eisai Inc. Fycompa (perampanel) tablets prescribing information. Woodcliff Lake, NJ; 2014 Sep.

2. French JA, Krauss GL, Biton V et al. Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. Neurology. 2012; 79:589-96. [PubMed 22843280]

3. French JA, Krauss GL, Steinhoff BJ et al. Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: results of randomized global phase III study 305. Epilepsia. 2013; 54:117-25. [PubMed 22905857]

4. Krauss GL, Serratosa JM, Villanueva V et al. Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures. Neurology. 2012; 78:1408-15. [PubMed 22517103]

5. Krauss GL, Perucca E, Ben-Menachem E et al. Long-term 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. [PubMed 24867391]

6. Steinhoff BJ, Ben-Menachem E, Ryvlin P et al. Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: a pooled analysis of three phase III studies. Epilepsia. 2013; 54:1481-9. [PubMed 23663001]

7. Drug Enforcement Administration (DEA), Department of Justice. Schedules of controlled substances: placement of perampanel into schedule III. 21 CFR Part 1308. Final Rule. [Docket No. DEA-374]. Fed Regist. 2013; 78 (231): 72013-16.

8. Food and Drug Administration. Center for Drug Evaluation and Research: Application number 202834Orig1s000: Summary Review. From FDA website.

9. Eisai, Woodcliff Lake, NJ: Personal communication.

10. Food and Drug Administration. FDA Alert: Information for healthcare professionals: suicidal behavior and ideation and antiepileptic drugs. Rockville, MD; 2008 Jan 31; updated 2008 Dec 16. From the FDA website.

11. Food and Drug Administration. FDA News: FDA alerts health care providers to risk of suicidal thoughts and behavior with antiepileptic medications. Rockville, MD; 2008 Jan 31. From the FDA website.

12. Food and Drug Administration. Suicidal behavior and ideation and antiepileptic drugs: update 5/5/2009. Rockville, MD; 2009 May 5. From the FDA website. Accessed 2012 May 4.

13. Krauss GL, Bar M, Biton V et al. Tolerability and safety of perampanel: two randomized dose-escalation studies. Acta Neurol Scand. 2012; 125:8-15. [PubMed 21883097]

14. Plosker GL. Perampanel: as adjunctive therapy in patients with partial-onset seizures. CNS Drugs. 2012; 26:1085-96. [PubMed 23179642]

15. Zaccara G, Giovannelli F, Cincotta M et al. AMPA receptor inhibitors for the treatment of epilepsy: the role of perampanel. Expert Rev Neurother. 2013; 13:647-55. [PubMed 23739002]

16. Shih JJ, Tatum WO, Rudzinski LA. New drug classes for the treatment of partial onset epilepsy: focus on perampanel. Ther Clin Risk Manag. 2013; 9:285-93. [PubMed 23874099]

17. Ko D, Ramsay RE. Perampanel: expanding therapeutic options for patients with medically refractory secondary generalized convulsive seizures. Acta Neurol Scand Suppl. 2013; :36-43. [PubMed 23480155]

18. Hsu WW, Sing CW, He Y et al. Systematic review and meta-analysis of the efficacy and safety of perampanel in the treatment of partial-onset epilepsy. CNS Drugs. 2013; 27:817-27. [PubMed 23918722]

19. Rogawski MA, Hanada T. Preclinical pharmacology of perampanel, a selective non-competitive AMPA receptor antagonist. Acta Neurol Scand Suppl. 2013; :19-24. [PubMed 23480152]

20. Zaccara G, Giovannelli F, Cincotta M et al. The adverse event profile of perampanel: meta-analysis of randomized controlled trials. Eur J Neurol. 2013; 20:1204-11. [PubMed 23607817]

21. Gidal BE, Ferry J, Majid O et al. Concentration-effect relationships with perampanel in patients with pharmacoresistant partial-onset seizures. Epilepsia. 2013; 54:1490-7. [PubMed 23772853]

22. Rogawski MA. Revisiting AMPA receptors as an antiepileptic drug target. Epilepsy Curr. 2011; 11:56-63. [PubMed 21686307]

23. . Perampanel (Fycompa) for epilepsy. Med Lett Drugs Ther. 2014; 56:9-10. [PubMed 24662975]

24. Food and Drug Administration. FDA Application: Search Orphan Drug Designations and Approvals. Rockville, MD. From FDA website. Accessed 2014 Nov 9.

25. US Food and Drug Administration. Center for Drug Evaluation and Research. NDA number 202834: Clinical pharmacology review. From FDA website. Accessed 2014 Oct 24.

26. Hoppner AC, Fauser S, Kerling F. Clinical course of intoxication with the new anticonvulsant drug perampanel. Epileptic Disord. 2013; 15:362-4.

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