Perampanel 8 mg Tablet, Film Coated, 30-count — NDC 0480-7066-56 (Billing 00480-7066-56)
This is a package of 30 tablets of Perampanel 8 mg Tablet, Film Coated from Teva Pharmaceuticals, Inc., marketed since May 2025 and currently FDA-listed; retail pharmacies pay about $18.38 per tablet (NADAC). It is this product's only package size.
Other active recalls for Perampanel (different manufacturers) — 1 · tap to view
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 069991
- GCN: 33274
- HICL (First Databank): 039628
- AHFS class code: 28:12.92.00
- RxCUI (RxNorm): 1356557
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Noncompetitive AMPA Glutamate Receptor Antagonist class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
Perampanel is used to treat certain types of partial onset seizures (seizures that involve only one part of the brain) in adults and children 4 years of age and older. It is also used in combination with other medications to treat certain types of primary generalized tonic-clonic seizures (formerly known as a grand mal seizure; seizure that involves the entire body) in adults and children 12 years of age or older. Perampanel is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in the brain.
Read the full MedlinePlus article ↗- It treats partial-onset seizures in people with epilepsy age 4 and older. It is also used as an add-on medicine for primary generalized tonic-clonic seizures in people 12 and older...
- Take it by mouth once a day at bedtime, as tablets or liquid suspension. If you use the liquid, measure it with the syringe and adaptor that come with it. Your dose is usually rais...
- Dizziness, sleepiness, tiredness, irritability, nausea, headache, and weight gain are common. Falls and balance trouble can also happen, especially in older adults. Many of these s...
- This medicine has a boxed warning for aggression, hostility, anger, irritability, and even threats to harm others. These can happen even if you have never had such problems. Call y...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Perampanel — tap one for details:
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $18.377 | $551.30 / 30 tablets |
| Medicaid paysCMS SDUD · 12 mo | $30.60 | $918.04 / 30 tablets |
| Medicare drug plans payPart D · Q2 2026 | $26.77 | $803.07 / 30 tablets |
Where does this data come from?
- CMS NADAC weekly file · file of Sep 30, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q1 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 00480-7066-56 You're viewing this Main listing | 30 TABLET, FILM COATED in 1 BOTTLE | 2025-05-29 | — | Active |
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Perampanel 8 mgthis 00480-7066-56 | Teva | 30 tablets | $18.377 | AB | Availability likely | — |
| Perampanel 8 mg 72205-0224-30 | Novadoz | 30 tablets | $18.377 | AB | Availability likely | — |
| Fycompa 8 mg 62856-0278-30 | Eisai | 30 tablets | $39.087 | AB | Availability likely | +113% |
| Fycompa 8 mg 69616-0278-30 | Catalyst | 30 tablets | $39.087 | AB | Availability likely | +113% |
| Perampanel 8 mg 51672-4207-02 | Sun | 10 tablets | — | AB | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Sep 3, 2026
- CMS NADAC weekly file · file of Sep 30, 2026
Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
- FDA Orange Book · refreshed Sep 3, 2026
What it looks like
Where does this data come from?
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 2S7830E561
Crospovidone is a synthetic polymer derived from povidone. It acts as a disintegrant, helping the tablet or capsule break apart quickly in the stomach so the active ingredient can be absorbed.
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UNII 4AQJ3LG584
A synthetic blue dye combined with aluminum to create a stable colorant. It's used in medicines and supplements to add blue color or create specific shades for product identification and appearance.
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UNII 1K09F3G675
Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII 2165RE0K14
A plant-based thickener made from cellulose that helps control how quickly the medicine dissolves and releases its active ingredient. It also binds ingredients together and improves the tablet's texture and handling during manufacturing.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII 4R4HFI6D95
Polyethylene glycol 4000 is a synthetic polymer derived from petroleum. It serves as a binder, filler, and lubricant in solid dosage forms, and helps control how quickly the medicine dissolves.
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UNII 532B59J990
Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.
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UNII U725QWY32X
Povidone K30 is a synthetic polymer made from petroleum. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in the stomach so the medicine can be absorbed.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
12 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 1, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
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Manufacturer & labeler
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS Serious or life-threatening psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger, and homicidal ideation and threats have been reported in patients taking perampanel tablets ( 5.1 ). These reactions occurred in patients with and without prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression ( 5.1 ). 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 while taking perampanel tablets or after discontinuing perampanel tablets ( 5.1 ).
Closely monitor patients particularly during the titration period and at higher doses ( 5.1 ). Perampanel tablets should be reduced if these symptoms occur and should be discontinued immediately if symptoms are severe or are worsening ( 5.1 ). WARNING: SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS See full prescribing information for complete boxed warning.
Serious or life-threatening psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger, and homicidal ideation and threats have been reported in patients taking perampanel tablets ( 5.1 ) Monitor patients for these reactions as well as for changes in mood, behavior, or personality that are not typical for the patient, particularly during the titration period and at higher doses ( 5.1 ) Perampanel tablets should be reduced if these symptoms occur and should be discontinued immediately if symptoms are severe or are worsening ( 5.1 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Perampanel tablets, a non-competitive AMPA glutamate receptor antagonist, are indicated for: Treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy 4 years of age and older ( 1.1 ) Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older ( 1.2 )
1.1Partial-Onset Seizures Perampanel tablets are indicated for the treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy 4 years of age and older.
1.2Primary Generalized Tonic-Clonic Seizures Perampanel tablets are indicated as adjunctive therapy for the treatment of primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Dosing in the absence of moderate or strong CYP3A4 inducers Starting dose: 2 mg once daily orally at bedtime ( 2.1 , 2.2 ) May increase dose based on clinical response and tolerability by increments of 2 mg once daily no more frequently than at weekly intervals ( 2.1 , 2.2 ) Recommended maintenance dose in monotherapy or adjunctive therapy for partial-onset seizures: 8 mg to 12 mg once daily at bedtime ( 2.1 ) Recommended maintenance dose in adjunctive therapy for primary generalized tonic-clonic seizures: 8 mg once daily at bedtime ( 2.2 ) Dosing in the presence of concomitant moderate or strong CYP3A4 inducers: See section
2.3Specific Populations Mild and Moderate Hepatic Impairment: Maximum recommended daily dose is 6 mg (mild) and 4 mg (moderate) once daily at bedtime ( 2.4 ) Severe Hepatic Impairment: Not recommended ( 2.4 ) Severe Renal Impairment or on Hemodialysis: Not recommended ( 2.5 ) Elderly: Increase dose no more frequently than every 2 weeks ( 2.6 )
2.1Dosage for Partial-Onset Seizures Monotherapy or Adjunctive Therapy The recommended starting dosage of perampanel tablets in adults and pediatric patients 4 years of age and older is 2 mg once daily taken orally at bedtime. Increase dosage no more frequently than at weekly intervals by increments of 2 mg once daily based on individual clinical response and tolerability. The recommended maintenance dose range is 8 mg to 12 mg once daily, although some patients may respond to a dose of 4 mg daily.
A dose of 12 mg once daily resulted in somewhat greater reductions in seizure rates than the dose of 8 mg once daily, but with a substantial increase in adverse reactions. Dosage adjustment is recommended with concomitant use of moderate or strong CYP3A4 enzyme inducing drugs, which include certain antiepileptic drugs (AEDs) [see Dosage and Administration ( 2.3 )] .
2.2Dosage for Primary Generalized Tonic-Clonic Seizures Adjunctive Therapy The recommended starting dosage of perampanel tablets in adults and pediatric patients 12 years of age and older is 2 mg once daily taken orally at bedtime. Increase dosage no more frequently than at weekly intervals by increments of 2 mg once daily based on individual clinical response and tolerability. The recommended maintenance dose is 8 mg once daily taken at bedtime.
Patients who are tolerating perampanel tablets at 8 mg once daily and require further reduction of seizures may benefit from a dose increase up to 12 mg once daily if tolerated. Dosage adjustment is recommended with concomitant use of moderate or strong CYP3A4 enzyme inducing drugs, which include certain AEDs [see Dosage and Administration ( 2.3 )] .
2.3Dosage Modifications with Concomitant Use of Moderate or Strong CYP3A4 Enzyme Inducers Moderate and strong CYP3A4 inducers, including enzyme-inducing AEDs such as phenytoin, carbamazepine, and oxcarbazepine, cause a reduction in perampanel plasma levels [see Drug Interactions ( 7.2 ), Clinical Pharmacology ( 12.3 )] . Therefore, in adults and pediatric patients 4 years of age and older receiving these concomitant enzyme-inducing drugs, the recommended starting dosage of perampanel tablets is 4 mg once daily taken orally at bedtime.
Increase dosage by increments of 2 mg once daily based on individual clinical response and tolerability, no more frequently than at weekly intervals. A maintenance dose has not been established in clinical trials. The highest dose studied in patients on concomitant enzyme-inducing AEDs was 12 mg once daily.
When moderate or strong CYP3A4 inducers are introduced or withdrawn from a patient’s treatment regimen, the patient should be closely monitored for clinical response and tolerability. Dose adjustment of perampanel tablets may be necessary.
2.4Dosage Adjustment in Patients with Hepatic Impairment In patients with mild and moderate hepatic impairment, the starting dose of perampanel tablets is 2 mg once daily. Increase dosage by increments of 2 mg once daily… [Excerpted — this section continues on DailyMed.]
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS 2 mg: beige, round, biconvex, film-coated tablets, debossed with “TV” on one side and with “W2” on the other side. 4 mg: pink, round, biconvex, film-coated tablets, debossed with “TV” on one side and with “W4” on the other side. 6 mg: pink, round, biconvex, film-coated tablets, debossed with “TV” on one side and with “W6” on the other side.
8 mg: purple, round, biconvex, film-coated tablets, debossed with “TV” on one side and with “W8” on the other side. 10 mg: green, round, biconvex, film-coated tablets, debossed with “TV” on one side and with “W0” on the other side. 12 mg: light blue, round, biconvex, film-coated tablets, debossed with “TV” on one side and with “W1” on the other side.
Tablets: 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Suicidal Behavior and Ideation: Monitor for suicidal thoughts or behavior ( 5.2 ) Neurologic Effects: Monitor for dizziness, gait disturbance, somnolence, and fatigue ( 5.3 ) Patients should use caution when driving or operating machinery ( 5.3 ) Falls: Monitor for falls and injuries ( 5.4 ) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ Hypersensitivity: Discontinue if no alternate etiology ( 5.5 ) Withdrawal of Antiepileptic Drugs: In patients with epilepsy, there may be an increase in seizure frequency ( 5.6 )
5.1Serious Psychiatric and Behavioral Reactions In the controlled partial-onset seizure clinical trials, hostility- and aggression-related adverse reactions occurred in 12% and 20% of patients randomized to receive perampanel at doses of 8 mg and 12 mg per day, respectively, compared to 6% of patients in the placebo group. These effects were dose-related and generally appeared within the first 6 weeks of treatment, although new events continued to be observed through more than 37 weeks. Perampanel-treated patients experienced more hostility- and aggression-related adverse reactions that were serious, severe, and led to dose reduction, interruption, and discontinuation more frequently than placebo-treated patients.
In general, in placebo-controlled partial-onset seizure clinical trials, neuropsychiatric events were reported more frequently in patients being treated with perampanel than in patients taking placebo. These events included irritability, aggression, anger, and anxiety, which occurred in 2% or greater of perampanel-treated patients and twice as frequently as in placebo-treated patients. Other symptoms that occurred with perampanel and were more common than with placebo included belligerence, affect lability, agitation, and physical assault.
Some of these events were reported as serious and life-threatening. Homicidal ideation and/or threat were exhibited in 0.1% of 4,368 perampanel-treated patients in controlled and open label trials, including non-epilepsy trials. Homicidal ideation and/or threat have also been reported postmarketing in patients treated with perampanel.
In the partial-onset seizure clinical trials, these events occurred in patients with and without prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression. Some patients experienced worsening of their preexisting psychiatric conditions. Patients with active psychotic disorders and unstable recurrent affective disorders were excluded from the clinical trials.
The combination of alcohol and perampanel significantly worsened mood and increased anger. Patients taking perampanel should avoid the use of alcohol [see Drug Interactions ( 7.3 )] . Similar serious psychiatric and behavioral events were observed in the primary generalized tonic-clonic seizure clinical trial.
In healthy volunteers taking perampanel, observed psychiatric events included paranoia, euphoric mood, agitation, anger, mental status changes, and disorientation/confusional state. In the non-epilepsy trials, psychiatric events that occurred in perampanel-treated patients more often than placebo-treated patients included disorientation, delusion, and paranoia. In the postmarketing setting, there have been reports of psychosis (acute psychosis, hallucinations, delusions, paranoia) and delirium (delirium, confusional state, disorientation, memory impairment) in patients treated with perampanel [see Adverse Reactions ( 6.2 )] .
Patients, their caregivers, and families should be informed that perampanel may increase the risk of psychiatric events. Patients should be monitored during treatment and for at least 1 month after the last dose of perampanel, and especially when taking higher doses and during the initial few weeks of drug therapy (titration period) or at other times of dose increases. Dose of perampanel should be reduced if these symptoms occur.
Permane… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: Serious Psychiatric and Behavioral Reactions [see Warnings and Precautions ( 5.1 )] Suicidal Behavior and Ideation [see Warnings and Precautions ( 5.2 )] Neurologic Effects [see Warnings and Precautions ( 5.3 )] Falls [see Warnings and Precautions ( 5.4 )] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity [see Warnings and Precautions ( 5.5 )] Most common adverse reactions (≥ 5% and ≥ 1% higher than placebo) include dizziness, somnolence, fatigue, irritability, falls, nausea, weight gain, vertigo, ataxia, headache, vomiting, contusion, abdominal pain, and anxiety ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Partial-Onset Seizures Adult and Adolescent Patients (12 years of age and older) A total of 1,038 patients receiving perampanel (2 mg, 4 mg, 8 mg, or 12 mg once daily) constituted the safety population in the pooled analysis of the placebo-controlled trials (Studies 1, 2, and 3) in patients with partial-onset seizures.
Approximately 51% of patients were female, and the mean age was 35 years. Adverse Reactions Leading to Discontinuation In controlled clinical trials (Studies 1, 2, and 3), the rate of discontinuation as a result of an adverse reaction was 3%, 8%, and 19% in patients randomized to receive perampanel at the recommended doses of 4 mg, 8 mg, and 12 mg per day, respectively, and 5% in patients randomized to receive placebo [see Clinical Studies ( 14 )] . The adverse reactions most commonly leading to discontinuation (≥1% in the 8 mg or 12 mg perampanel group and greater than placebo) were dizziness, somnolence, vertigo, aggression, anger, ataxia, blurred vision, irritability, and dysarthria [see Warnings and Precautions ( 5.1 , 5.3 )] .
Most Common Adverse Reactions Table 2 gives the incidence in the controlled clinical trials (Studies 1, 2, and 3) of the adverse reactions that occurred in ≥2% of patients with partial-onset seizures in the perampanel 12 mg dose group and more frequent than placebo (in order of decreasing frequency for the 12 mg dose group). The most common dose-related adverse reactions in patients receiving perampanel at doses of 8 mg or 12 mg (≥4% and occurring at least 1% higher than the placebo group) included dizziness (36%), somnolence (16%), fatigue (10%), irritability (9%), falls (7%), nausea (7%), ataxia (5%), balance disorder (4%), gait disturbance (4%), vertigo (4%), and weight gain (4%).
For almost every adverse reaction, rates were higher on 12 mg and more often led to dose reduction or discontinuation. Table 2. Adverse Reactions in Pooled Placebo-Controlled Trials in Adult and Adolescent Patients with Partial-Onset Seizures (Studies 1, 2, and 3) (Reactions ≥ 2% of Patients in Highest Perampanel Dose (12 mg) Group and More Frequent than Placebo) Placebo n=442 % Perampanel 4 mg n=172 % 8 mg n=431 % 12 mg n=255 % Dizziness 9 16 32 43 Somnolence 7 9 16 18 Headache 11 11 11 13 Irritability 3 4 7 12 Fatigue 5 8 8 12 Falls 3 2 5 10 Ataxia 0 1 3 8 Nausea 5 3 6 8 Vertigo 1 4 3 5 Back pain 2 2 2 5 Dysarthria 0 1 3 4 Anxiety 1 2 3 4 Blurred vision 1 1 3 4 Gait disturbance 1 1 4 4 Weight gain 1 4 4 4 Cough 3 1 1 4 Upper respiratory tract infection 3 3 3 4 Vomiting 3 2 3 4 Hypersomnia 0 1 2 3 Anger <1 0 1 3 Aggression 1 1 2 3 Balance disorder 1 0 5 3 Diplopia 1 1 1 3 Head injury 1 1 1 3 Hypoaesthesia 1 0 0 3 Pain in extremity 1 0 2 3 Constipation 2 2 2 3 Myalgia 2 1 1 3 Coordination abnormal 0 1 <1 2 Euphoric mood 0 0 <1 2 Confusional state <1 1 1 2 Hyponatremia <1 0 0… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. When moderate or strong CYP3A4 inducers are introduced or withdrawn, monitor patients closely. Dose adjustment of perampanel may be necessary ( 2.3 , 7.2 )
7.1Contraceptives With concomitant use, perampanel at a dose of 12 mg per day reduced levonorgestrel exposure by approximately 40% [see Clinical Pharmacology ( 12.3 )] . Use of perampanel with contraceptives containing levonorgestrel may render them less effective. Additional non-hormonal forms of contraception are recommended [see Use in Specific Populations (8.3)] .
7.2Moderate and Strong CYP3A4 Inducers The concomitant use of known moderate and strong CYP3A4 inducers including carbamazepine, phenytoin, or oxcarbazepine with perampanel decreased the plasma levels of perampanel by approximately 50 to 67% [see Clinical Pharmacology ( 12.3 )] . The starting doses for perampanel should be increased in the presence of moderate or strong CYP3A4 inducers [see Dosage and Administration ( 2.3 )] . When these moderate or strong CYP3A4 inducers are introduced or withdrawn from a patient’s treatment regimen, the patient should be closely monitored for clinical response and tolerability.
Dose adjustment of perampanel may be necessary [see Dosage and Administration ( 2.3 )] .
7.3Alcohol and Other CNS Depressants The concomitant use of perampanel and CNS depressants including alcohol may increase CNS depression. A pharmacodynamic interaction study in healthy subjects found that the effects of perampanel on complex tasks such as driving ability were additive or supra-additive to the impairment effects of alcohol [see Clinical Pharmacology ( 12.3 )] . Multiple dosing of perampanel 12 mg per day also enhanced the effects of alcohol to interfere with vigilance and alertness, and increased levels of anger, confusion, and depression.
These effects may also be seen when perampanel is used in combination with other CNS depressants. Care should be taken when administering perampanel with these agents. Patients should limit activity until they have experience with concomitant use of CNS depressants (e.g., benzodiazepines, narcotics, barbiturates, sedating antihistamines).
Advise patients not to drive or operate machinery until they have gained sufficient experience on perampanel to gauge whether it adversely affects these activities.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm ( 8.1 )
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as perampanel, during pregnancy. Encourage women who are taking perampanel during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org. Risk Summary 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 [see Data] . In the U.S. general population the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.
Data Animal Data Oral administration of perampanel (1, 3, or 10 mg/kg/day) to pregnant rats throughout organogenesis resulted in an increase in visceral abnormalities (diverticulum of the intestine) at all doses tested; maternal toxicity was observed at the mid and high doses. In a dose-ranging study at higher oral doses (10, 30, or 60 mg/kg/day), embryo lethality and reduced fetal body weight were observed at the mid and high doses tested. The lowest dose tested (1 mg/kg/day) is similar to a human dose of 8 mg/day based on body surface area (mg/m 2 ).
Upon oral administration of perampanel (1, 3, or 10 mg/kg/day) to pregnant rabbits throughout organogenesis, embryo lethality and maternal toxicity were observed at the mid and high doses tested; the no-effect dose for embryo-fetal developmental toxicity in rabbit (1 mg/kg/day) is approximately 2 times a human dose of 8 mg/day based on body surface area (mg/m 2 ). Oral administration of perampanel (1, 3, or 10 mg/kg/day) to rats throughout gestation and lactation resulted in fetal and pup deaths at the mid and high doses (associated with maternal toxicity) and delayed sexual maturation in males and females at the highest dose tested.
No effects were observed on measures of neurobehavioral or reproductive function in the offspring. The no-effect dose for pre- and postnatal developmental toxicity in rat (1 mg/kg/day) is similar to a human dose of 8 mg/day based on body surface area (mg/m 2 ).
8.2Lactation Risk Summary There are no data on the presence of perampanel in human milk, the effects on the breastfed child, or the effects of the drug on milk production. 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 perampanel and any potential adverse effects on the breastfed child from perampanel or from the underlying maternal condition.
8.3Females and Males of Reproductive Potential Contraception Use of perampanel may reduce the efficacy of hormonal contraceptives containing levonorgestrel. Advise women taking perampanel who are using a levonorgestrel-containing contraceptive to use an additional non-hormonal form of contraception while using perampanel and for a month after discontinuation [see Drug Interactions ( 7.1 ), Clinical Pharmacology ( 12.3 )] .
8.4Pediatric Use Safety and effectiveness of perampanel for the treatment of partial-onset seizures have been established in pediatric patients 4 years of age and older. The safety and effectiveness of perampanel in patients 12 years of age and older was established by three randomized double-blind, placebo-controlled, multicenter studies, which included 72 pediatric patients between 12 and 16 years of age exposed to perampanel [see Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14.1 )] . Use of perampanel for the treatment of par… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as perampanel, during pregnancy. Encourage women who are taking perampanel during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org. Risk Summary 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 [see Data] . In the U.S. general population the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.
Data Animal Data Oral administration of perampanel (1, 3, or 10 mg/kg/day) to pregnant rats throughout organogenesis resulted in an increase in visceral abnormalities (diverticulum of the intestine) at all doses tested; maternal toxicity was observed at the mid and high doses. In a dose-ranging study at higher oral doses (10, 30, or 60 mg/kg/day), embryo lethality and reduced fetal body weight were observed at the mid and high doses tested. The lowest dose tested (1 mg/kg/day) is similar to a human dose of 8 mg/day based on body surface area (mg/m 2 ).
Upon oral administration of perampanel (1, 3, or 10 mg/kg/day) to pregnant rabbits throughout organogenesis, embryo lethality and maternal toxicity were observed at the mid and high doses tested; the no-effect dose for embryo-fetal developmental toxicity in rabbit (1 mg/kg/day) is approximately 2 times a human dose of 8 mg/day based on body surface area (mg/m 2 ). Oral administration of perampanel (1, 3, or 10 mg/kg/day) to rats throughout gestation and lactation resulted in fetal and pup deaths at the mid and high doses (associated with maternal toxicity) and delayed sexual maturation in males and females at the highest dose tested.
No effects were observed on measures of neurobehavioral or reproductive function in the offspring. The no-effect dose for pre- and postnatal developmental toxicity in rat (1 mg/kg/day) is similar to a human dose of 8 mg/day based on body surface area (mg/m 2 ).
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of perampanel for the treatment of partial-onset seizures have been established in pediatric patients 4 years of age and older. The safety and effectiveness of perampanel in patients 12 years of age and older was established by three randomized double-blind, placebo-controlled, multicenter studies, which included 72 pediatric patients between 12 and 16 years of age exposed to perampanel [see Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14.1 )] . Use of perampanel for the treatment of partial-onset seizures in pediatric patients 4 years to less than 12 years of age is supported by evidence from adequate and well-controlled studies of perampanel in patients 12 years of age and older with partial onset seizures, pharmacokinetic data from adult and pediatric patients, and safety data in 225 pediatric patients 4 years to less than 12 years of age treated with perampanel [see Adverse Reactions ( 6.1 ) and Clinical Pharmacology ( 12.3 )] .
The safety and efficacy of perampanel for the adjunctive therapy of primary generalized tonic-clonic seizures in pediatric patients 12 years of age and older was established in a single randomized double-blind, placebo-controlled, multicenter trial (n=164), which included 11 pediatric patients 12 to 16 years of age exposed to perampanel; an additional 6 patients were treated with perampanel in the open-label extension of the study [see Clinical Studies ( 14.2 )] . The safety and effectiveness of perampanel for the treatment of partial-onset seizures in pediatric patients less than 4 years of age or for the treatment of primary generalized tonic-clonic seizures in pediatric patients less than 12 years of age have not been established.
Juvenile Animal Data Oral administration of perampanel (1, 3, 3/10/30 mg/kg/day; high dose increased on postnatal days [PND] 28 and 56) to young rats for 12 weeks starting on PND 7 resulted in reduced body weight, reduced growth, neurobehavioral impairment (water maze performance and auditory startle habituation) at the mid and high doses, and delayed sexual maturation at the high doses. CNS signs (reduced activity, incoordination, excessive grooming/scratching), pup death, decreased hindlimb splay, and decreased hindlimb grip strength were observed at all doses.
Effects on pup body weight, pup growth, hindlimb splay, impairment in the water maze performance, and auditory startle persisted after dosing was stopped. A no-effect dose for postnatal developmental toxicity was not identified in this study. Oral administration of perampanel (1, 5, 5/10 mg/kg/day; high dose increased on PND 56) to juvenile dogs for 33 weeks, starting on PND 42, resulted in CNS signs (incoordination, excessive grooming/licking/scratching, spatial disorientation, and/or ataxic gait) at all doses tested.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of perampanel did not include sufficient numbers of patients aged 65 and over to determine the safety and efficacy of perampanel in the elderly population. Because of increased likelihood for adverse reactions in the elderly, dosing titration should proceed slowly in patients aged 65 years and older [see Dosage and Administration ( 2.5 )] .
🆘 Overdosage ▾
10 OVERDOSAGE The highest reported overdose of perampanel was 300 mg. Events reported after perampanel overdose include somnolence, stupor, coma, psychiatric or behavioral reactions, altered mental status, and dizziness or gait disturbances. There is no available specific antidote to the overdose reactions of perampanel.
In the event of overdose, standard medical practice for the management of any overdose should be used. An adequate airway, oxygenation, and ventilation should be ensured; monitoring of cardiac rhythm and vital sign measurement is recommended. A certified poison control center should be contacted for updated information on the management of overdose with perampanel.
Due to its long half-life, the reactions caused by perampanel could be prolonged.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Perampanel is a non-competitive antagonist of the ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor on post-synaptic neurons. Glutamate is the primary excitatory neurotransmitter in the central nervous system and is implicated in a number of neurological disorders caused by neuronal over excitation. The precise mechanism by which perampanel exerts its antiepileptic effects in humans is unknown.
12.2Pharmacodynamics Psychomotor Performance In a healthy volunteer study to assess the effects of perampanel tablets on psychomotor performance using a standard battery of assessments including simulated driving, single and multiple daily doses of perampanel 4 mg did not impair simple psychomotor tasks, driving performance, or sensorimotor coordination. Single and multiple doses of 8 mg and 12 mg impaired psychomotor performance in a dose-related manner. Car handling ability was impaired after dosing of perampanel 12 mg, but postural stability was not significantly impaired.
Performance testing returned to baseline within 2 weeks of cessation of perampanel dosing. Interactions with Alcohol In the above study ( see Psychomotor Performance ), when administered to healthy subjects receiving alcohol to achieve a blood concentration of 80 to 100 mg/100 mL, perampanel consistently impaired simple psychomotor performance after single doses of 4 to 12 mg, and after 21 days of multiple 12 mg/day doses. The effects of perampanel on complex tasks such as driving ability were additive or supra-additive to the impairment effects of alcohol.
Perampanel enhanced the effects of alcohol on vigilance and alertness, and increased levels of anger, confusion, and depression. Potential to Prolong QT Interval In a placebo-controlled thorough QT study of perampanel in healthy subjects, there was no evidence that perampanel caused QT interval prolongation of clinical significance at doses of 6 or 12 mg (i.e., the upper bound of the 95% confidence interval for the largest placebo-adjusted baseline-corrected QTc was below 10 msec). The exposures observed with the 12 mg dose in this study will not cover the exposures expected in patients with hepatic impairment taking doses over 6 mg/day.
At the highest recommended dose (12 mg), perampanel did not prolong the QTc interval to any clinically relevant extent.
12.3Pharmacokinetics Pharmacokinetics of perampanel are similar in healthy subjects, patients with partial-onset seizures, and patients with primary generalized tonic-clonic seizures. The half-life of perampanel is about 105 hours, so that steady state is reached in about 2 to 3 weeks. AUC of perampanel increased in a dose-proportional manner after single-dose administration of 0.2 to 12 mg tablets and after multiple-dose administration of 1 to 12 mg tablets once daily.
Perampanel oral suspension has comparable bioavailability to perampanel tablets under steady state. Both formulations may be used interchangeably. The pharmacokinetics of perampanel are similar when used as monotherapy or as adjunctive therapy for the treatment of partial-onset seizures (in the absence of concomitant moderate or strong CYP3A4 inducers).
Absorption Perampanel is rapidly and completely absorbed after oral administration with negligible first-pass metabolism. Median time to reach peak concentration (t max ) ranged from 0.5 to 2.5 hours under fasted condition. Coadministration of perampanel tablet with a high fat meal had no impact on the total exposure (AUC 0-inf ) of perampanel and reduced the peak plasma concentration (C max ) of perampanel by 11% to 40%.
The t max was delayed by approximately 1 to 3 hours in fed state compared to that under fasted conditions. Distribution Data from in vitro studies indicate that, in the concentration range of 20 to 2000 ng/mL, perampanel is approximately 95 to 96% bound to plasma proteins, mainly bound to albumin and α1-acid glycoprotein. Blood to plasma… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action Perampanel is a non-competitive antagonist of the ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor on post-synaptic neurons. Glutamate is the primary excitatory neurotransmitter in the central nervous system and is implicated in a number of neurological disorders caused by neuronal over excitation. The precise mechanism by which perampanel exerts its antiepileptic effects in humans is unknown.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Perampanel tablets 2 mg are beige, round, biconvex, film-coated tablets, debossed with “TV” on one side and with “W2” on the other side. They are supplied as follows: Bottles of 30: NDC 0480-7062-56 4 mg are pink, round, biconvex, film-coated tablets, debossed with “TV” on one side and with “W4” on the other side. They are supplied as follows: Bottles of 30: NDC 0480-7063-56 6 mg are pink, round, biconvex, film-coated tablets, debossed with “TV” on one side and with “W6” on the other side.
They are supplied as follows: Bottles of 30: NDC 0480-7065-56 8 mg are purple, round, biconvex, film-coated tablets, debossed with “TV” on one side and with “W8” on the other side. They are supplied as follows: Bottles of 30: NDC 0480-7066-56 10 mg are green, round, biconvex, film-coated tablets, debossed with “TV” on one side and with “W0” on the other side. They are supplied as follows: Bottles of 30: NDC 0480-7067-56 12 mg are light blue, round, biconvex, film-coated tablets, debossed with “TV” on one side and with “W1” on the other side.
They are supplied as follows: Bottles of 30: NDC 0480-7068-56
16.2Storage Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
📋 Description ▾
11 DESCRIPTION Perampanel tablets contain perampanel, a non-competitive AMPA receptor antagonist. The chemical name of the active ingredient is 2-(1′,6′-dihydro-6′-oxo-1′-phenyl[2,3′-bipyridin]-5′-yl)-benzonitrile The molecular formula is C 23 H 15 N 3 O and the molecular weight is 349.38 (for anhydrous perampanel). It is a white to yellowish solid.
It is freely soluble in dichloromethane and N-methyl-2-pyrrolidone, sparingly soluble in acetone and acetonitrile, slightly soluble in ethanol, ethyl acetate, methanol, and toluene, very slightly soluble in 1-octanol and diethyl ether, and practically insoluble in n-hexane and water. The chemical structure is: Perampanel tablets are round, biconvex, film-coated tablets containing 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, or 12 mg of perampanel. Tablets contain the following inactive ingredients: crospovidone, lactose monohydrate, low substituted hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol – part. hydrolyzed, povidone, talc, and titanium dioxide.
Additionally, the 2 mg, 4 mg, 6 mg, and 8 mg contain iron oxide red, the 2 mg and 10 mg contain iron oxide yellow, and the 8 mg, 10 mg, and 12 mg contain FD&C Blue No. 2 (indigo carmine) Aluminum Lake. new
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Serious Psychiatric and Behavioral Reactions Counsel patients, families, and caregivers of patients of the need to monitor for the emergence of anger, aggression, hostility, hallucinations, delusions, confusion, unusual changes in mood, personality, or behavior, and other behavioral symptoms. Advise them to report any such symptoms immediately to their healthcare providers [see Warnings and Precautions ( 5.1 )] .
Suicidal Thinking and Behavior Counsel patients, their caregivers, and families that AEDs, including perampanel tablets, may increase the risk of suicidal thinking and behavior and advise them of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Instruct patients, caregivers, and families to report behaviors of concern immediately to healthcare providers [see Warnings and Precautions ( 5.2 )] .
Neurologic Effects: Dizziness, Gait Disturbance, Somnolence, and Fatigue Counsel patients that perampanel tablets may cause dizziness, gait disturbance, somnolence, and fatigue. Advise patients taking perampanel tablets not to drive, operate complex machinery, or engage in other hazardous activities until they have become accustomed to any such effects associated with perampanel tablets [see Warnings and Precautions ( 5.3 )]. Falls Counsel patients that perampanel tablets may cause falls and injuries [see Warnings and Precautions ( 5.4 )] .
DRESS/Multi-organ Hypersensitivity Instruct patients that a fever associated with signs of other organ system involvement (e.g., rash, lymphadenopathy, hepatic dysfunction) may be drug-related and should be reported to their healthcare provider immediately [see Warnings and Precautions ( 5.5 )] . Withdrawal of Antiepileptic Drugs Counsel patients that abrupt discontinuation of perampanel tablets may increase seizure frequency [see Warnings and Precautions ( 5.6 )] . Contraceptives Counsel females of reproductive potential that perampanel tablets may decrease efficacy of contraceptives containing levonorgestrel, and advise them to use an additional non-hormonal form of contraception while using perampanel tablets and for a month after discontinuation [see Drug Interactions ( 7.1 ), Use in Specific Populations ( 8.3 )] .
Alcohol and Other CNS Depressants Counsel patients that perampanel tablets may enhance the impairment effects of alcohol. These effects may also be seen if perampanel tablets are taken with other CNS depressants [see Drug Interactions ( 7.3 )] . Missed Doses Counsel patients that if they miss a dose, they should resume dosing the following day at their prescribed daily dose.
Instruct patients to contact their physician if more than one day of dosing is missed. Controlled Substance Counsel patients that perampanel tablets are a controlled substance that can be misused and abused [see Drug Abuse and Dependence ( 9.1 )] . Pregnancy Registry Advise women who are exposed to perampanel during pregnancy that there is a pregnancy exposure registry that monitors pregnancy outcomes.
Encourage these patients to enroll in the NAAED Pregnancy Registry [see Use in Specific Populations ( 8.1 )] . Dispense with Medication Guide available at: www.tevausa.com/medguides Manufactured In Croatia By: Pliva Hrvatska d.o.o. Zagreb, Croatia Manufactured For: Teva Pharmaceuticals Parsippany, NJ 07054 Iss.
9/2024
💬 Medication Guide ▾
Dispense with Medication Guide available at: www.tevausa.com/medguides MEDICATION GUIDE Perampanel (per am′ pa nel) Tablets for oral use, CIII What is the most important information I should know about perampanel tablets? 1. Perampanel tablets may cause mental (psychiatric) problems, including: new or worse aggressive behavior (including homicidal behavior), hostility, anger, anxiety, or irritability being suspicious or distrustful (believing things that are not true) seeing objects or hearing things that are not there confusion difficulty with memory other unusual or extreme changes in behavior or mood Tell your healthcare provider right away if you have any new or worsening mental problems while taking perampanel tablets.
2. Like other antiepileptic drugs, perampanel tablets may cause suicidal thoughts or actions in a very small number of people, about 1 in 500. Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you: thoughts about suicide or dying new or worse depression feeling agitated or restless trouble sleeping (insomnia) acting aggressive, being angry, or violent an extreme increase in activity and talking (mania) attempt to commit suicide new or worse anxiety panic attacks new or worse irritability acting on dangerous impulses other unusual changes in behavior or mood Suicidal thoughts or actions can be caused by things other than medicines.
If you have suicidal thoughts or actions, your healthcare provider may check for other causes. How can I watch for early symptoms of suicidal thoughts and actions? Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.
Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you are worried about symptoms. Do not stop perampanel tablets without first talking with a healthcare provider.
Stopping perampanel tablets suddenly can cause serious problems. Stopping perampanel tablets suddenly can cause you to have seizures more often. What are perampanel tablets?
Perampanel tablets are a prescription medicine used: to treat partial-onset seizures with or without secondarily generalized seizures in people with epilepsy who are 4 years of age and older with other medicines to treat primary generalized tonic-clonic seizures in people with epilepsy who are 12 years of age and older Perampanel tablets are a controlled substance (CIII) because they can be abused or lead to drug dependence. Keep your perampanel tablets in a safe place to protect them from theft. Never give your perampanel tablets to anyone else because they may harm them.
Selling or giving away this medicine is against the law. It is not known if perampanel tablets are safe and effective for partial onset seizures in children under 4 years of age or for primary generalized tonic clonic seizures in patients under 12 years of age. Before taking perampanel tablets, tell your healthcare provider about all of your medical conditions, including if you: have or have had depression, mood problems, aggressive or hostile behavior (for example, homicidal behavior), suicidal thoughts or behavior, or other psychiatric problems have liver or kidney problems drink alcohol have abused prescription medicines, street drugs, or alcohol in the past are pregnant or plan to become pregnant.
It is not known if perampanel will harm your unborn baby. If you become pregnant while taking perampanel tablets, talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334 or go to http://www.aedpregnancyregistry.org.
The purpose of this registry is to collect information about the safety of perampanel tablets and other antiepileptic medicine during pregnancy. are breastfeeding or plan to breastfeed. It is not known if perampanel passes into your breast milk.… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Pharmacokinetics of perampanel are similar in healthy subjects, patients with partial-onset seizures, and patients with primary generalized tonic-clonic seizures. The half-life of perampanel is about 105 hours, so that steady state is reached in about 2 to 3 weeks. AUC of perampanel increased in a dose-proportional manner after single-dose administration of 0.2 to 12 mg tablets and after multiple-dose administration of 1 to 12 mg tablets once daily.
Perampanel oral suspension has comparable bioavailability to perampanel tablets under steady state. Both formulations may be used interchangeably. The pharmacokinetics of perampanel are similar when used as monotherapy or as adjunctive therapy for the treatment of partial-onset seizures (in the absence of concomitant moderate or strong CYP3A4 inducers).
Absorption Perampanel is rapidly and completely absorbed after oral administration with negligible first-pass metabolism. Median time to reach peak concentration (t max ) ranged from 0.5 to 2.5 hours under fasted condition. Coadministration of perampanel tablet with a high fat meal had no impact on the total exposure (AUC 0-inf ) of perampanel and reduced the peak plasma concentration (C max ) of perampanel by 11% to 40%.
The t max was delayed by approximately 1 to 3 hours in fed state compared to that under fasted conditions. Distribution Data from in vitro studies indicate that, in the concentration range of 20 to 2000 ng/mL, perampanel is approximately 95 to 96% bound to plasma proteins, mainly bound to albumin and α1-acid glycoprotein. Blood to plasma ratio of perampanel is 0.55 to 0.59.
Metabolism Perampanel is extensively metabolized via primary oxidation and sequential glucuronidation. Oxidative metabolism is primarily mediated by CYP3A4/5 and to a lesser extent by CYP1A2 and CYP2B6, based on results of in vitro studies using recombinant human CYPs and human liver microsomes. Other CYP enzymes may also be involved.
Following administration of radiolabeled perampanel, unchanged perampanel accounted for 74 to 80% of total radioactivity in systemic circulation, whereas only trace amounts of individual perampanel metabolites were detected in plasma. Elimination Following administration of a radiolabeled perampanel tablet dose to 8 healthy elderly subjects, 22% of administered radioactivity was recovered in the urine and 48% in the feces. In urine and feces, recovered radioactivity was primarily composed of a mixture of oxidative and conjugated metabolites.
Population pharmacokinetic analysis of pooled data from 19 Phase 1 studies reported that t 1/2 of perampanel was 105 hours on average. Apparent clearance of perampanel in healthy subjects and patients was approximately 12 mL/min. Specific Populations Hepatic Impairment The pharmacokinetics of perampanel following a single 1 mg tablet dose were evaluated in 12 subjects with mild and moderate hepatic impairment (Child-Pugh A and B, respectively) compared with 12 demographically matched healthy subjects.
The total (free and protein bound) exposure (AUC 0-inf ) of perampanel was 50% greater in subjects with mild hepatic impairment and more than doubled (2.55-fold) in subjects with moderate hepatic impairment compared to their healthy controls. The AUC 0-inf of free perampanel in subjects with mild and moderate hepatic impairment was 1.8-fold and 3.3-fold, respectively, of those in matched healthy controls. The t 1/2 was prolonged in subjects with mild impairment (306 vs.
125 hours) and moderate impairment (295 vs. 139 hours). Perampanel has not been studied in subjects with severe hepatic impairment [see Dosage and Administration ( 2.4 ), Use in Specific Populations ( 8.6 )] .
Renal Impairment A dedicated study has not been conducted to evaluate the pharmacokinetics of perampanel in patients with renal impairment. Population pharmacokinetic analysis was performed on pooled data from patients with partial-onset seizures and receiving perampanel tablets up to 12… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics Psychomotor Performance In a healthy volunteer study to assess the effects of perampanel tablets on psychomotor performance using a standard battery of assessments including simulated driving, single and multiple daily doses of perampanel 4 mg did not impair simple psychomotor tasks, driving performance, or sensorimotor coordination. Single and multiple doses of 8 mg and 12 mg impaired psychomotor performance in a dose-related manner. Car handling ability was impaired after dosing of perampanel 12 mg, but postural stability was not significantly impaired.
Performance testing returned to baseline within 2 weeks of cessation of perampanel dosing. Interactions with Alcohol In the above study ( see Psychomotor Performance ), when administered to healthy subjects receiving alcohol to achieve a blood concentration of 80 to 100 mg/100 mL, perampanel consistently impaired simple psychomotor performance after single doses of 4 to 12 mg, and after 21 days of multiple 12 mg/day doses. The effects of perampanel on complex tasks such as driving ability were additive or supra-additive to the impairment effects of alcohol.
Perampanel enhanced the effects of alcohol on vigilance and alertness, and increased levels of anger, confusion, and depression. Potential to Prolong QT Interval In a placebo-controlled thorough QT study of perampanel in healthy subjects, there was no evidence that perampanel caused QT interval prolongation of clinical significance at doses of 6 or 12 mg (i.e., the upper bound of the 95% confidence interval for the largest placebo-adjusted baseline-corrected QTc was below 10 msec). The exposures observed with the 12 mg dose in this study will not cover the exposures expected in patients with hepatic impairment taking doses over 6 mg/day.
At the highest recommended dose (12 mg), perampanel did not prolong the QTc interval to any clinically relevant extent.
🔬 Clinical Studies ▾
14 CLINICAL STUDIES
14.1Partial-Onset Seizures The efficacy of perampanel in partial-onset seizures, with or without secondary generalization, was studied in patients who were not adequately controlled with 1 to 3 concomitant AEDs in 3 randomized, double-blind, placebo-controlled, multicenter trials (Studies 1, 2, and 3) in adult and pediatric patients (12 years of age and older). All trials had an initial 6 week Baseline Period, during which patients were required to have more than five seizures in order to be randomized. The Baseline Period was followed by a 19 week Treatment Period consisting of a 6 week Titration Phase and a 13 week Maintenance Phase.
Patients in these 3 trials had a mean duration of epilepsy of approximately 21 years and a median baseline seizure frequency ranging from 9 to 14 seizures per 28 days. During the trials, more than 85% of patients were taking 2 to 3 concomitant AEDs with or without concurrent vagal nerve stimulation, and approximately 50% were on at least one AED known to induce CYP3A4, an enzyme critical to the metabolism of perampanel (i.e., carbamazepine, oxcarbazepine, or phenytoin), resulting in a significant reduction in perampanel’s serum concentration [see Drug Interactions ( 7.2 ), Clinical Pharmacology ( 12.3 )] .
Each study evaluated placebo and multiple perampanel dosages (see Figure 1). During the Titration period in all 3 trials, patients on perampanel received an initial 2 mg once daily dose, which was subsequently increased in weekly increments of 2 mg per day to the final dose. Patients experiencing intolerable adverse reactions were permitted to have their dose reduced to the previously tolerated dose.
The primary endpoint in Studies 1, 2, and 3 was the percent change in seizure frequency per 28 days during the Treatment Period as compared to the Baseline Period. The criterion for statistical significance was p<0.05. A statistically significant decrease in seizure rate was observed at doses of 4 to 12 mg per day.
Dose response was apparent at 4 to 8 mg with little additional reduction in frequency at 12 mg per day. Figure 1 . Median Percent Reduction in Seizure Frequency per 28 Days from Baseline to Treatment Period Tables 4 and 5 present an analysis combining data from all 3 studies, grouping patients based upon whether or not concomitant enzyme-inducing AEDs (carbamazepine, oxcarbazepine, or phenytoin) were used.
The analysis revealed a substantially reduced effect in the presence of inducers. Table 4. Median Percent Reduction for Combined Studies (Study 1, 2 and 3) Based on the Presence or Absence of Concomitant Enzyme-Inducing AEDs (carbamazepine, oxcarbazepine, phenytoin) a Without Enzyme-Inducing AEDs With Enzyme-Inducing AEDs Placebo % Perampanel % Placebo % Perampanel % 2 mg/day 16 23 14 16 4 mg/day 16 22 14 33 8 mg/day 19 45 12 24 12 mg/day 19 54 9 22 a Patients from Latin American region are excluded because of a significant treatment-by-region interaction due to high placebo response Table 5.
Responder Rate for Combined Studies (Study 1, 2 and 3) Based on the Presence or Absence of Concomitant Enzyme-Inducing AEDs (carbamazepine, oxcarbazepine, phenytoin) a,b Without Enzyme-Inducing AEDs With Enzyme-Inducing AEDs Placebo % Perampanel % Placebo % Perampanel % 2 mg/day 19 26 18 20 4 mg/day 19 35 18 26 8 mg/day 17 45 19 32 12 mg/day 15 54 21 33 a Patients from Latin American region are excluded because of a significant treatment-by-region interaction due to high placebo response b The proportion of patients with at least a 50% decrease in seizure frequency Figure 2 shows the proportion of patients with different percent reductions during the maintenance phase over baseline across all three trials.
Patients in whom the seizure frequency increased are shown at left as “worse.” Patients in whom the seizure frequency decreased are shown in the remaining four categories. Figure 2. Proportion of Patients Exhibiting Different Percent Reductions During the Maintenance Phase… [Excerpted — this section continues on DailyMed.]
🔒 Drug Abuse and Dependence ▾
9 DRUG ABUSE AND DEPENDENCE
9.1Controlled Substance Perampanel tablets contain perampanel and are listed as a Schedule III controlled substance.
9.2Abuse Prescription drug abuse is the intentional non-therapeutic use of a drug, even once, for its rewarding psychological or physiological effects. Drug addiction, which develops after repeated drug abuse, is characterized by a strong desire to take a drug despite harmful consequences, difficulty in controlling its use, giving a higher priority to drug use than to obligations, increased tolerance, and sometimes physical withdrawal. Drug abuse and drug addiction are separate and distinct from physical dependence (for example, abuse may not be accompanied by physical dependence) [see Drug Abuse and Dependence ( 9.3 )] .
Studies of human abuse potential were performed to evaluate the abuse potential of perampanel (8 mg, 24 mg, and 36 mg) as compared to alprazolam C-IV (1.5 mg and 3 mg), and oral ketamine C-III (100 mg) in recreational polydrug users. Supra-therapeutic doses of perampanel 24 and 36 mg produced responses for “Euphoria” that were similar to ketamine 100 mg and alprazolam 3 mg. For “High,” perampanel 24 mg and 36 mg produced responses comparable to ketamine 100 mg and significantly higher than both doses of alprazolam on a visual analog scale (VAS). “Drug Liking,” “Overall Drug Liking,” and “Take Drug Again” for perampanel were each statistically lower than ketamine 100 mg.
In addition, for “Bad Drug Effects,” perampanel 24 mg and 36 mg produced responses significantly higher than ketamine 100 mg. For “Sedation,” perampanel 24 and 36 mg produced responses similar to alprazolam 3 mg and higher than ketamine 100 mg. Additionally, on VAS measures related to dissociative phenomena such as “Floating,” “Spaced Out,” and “Detached,” perampanel at supratherapeutic doses produced responses similar to ketamine 100 mg and greater than both doses of alprazolam tested.
Of note, due to somnolence a number of subjects had missing data around T max of perampanel. The above described data might represent an underestimate of perampanel’s effects. The duration of effects of higher doses of perampanel on the majority of measures was much greater than alprazolam 3 mg and ketamine 100 mg.
In this study, the incidence of euphoria following perampanel administration 8 mg, 24 mg, and 36 mg was 37%, 46%, 46%, respectively, which was higher than alprazolam 3 mg (13%) but lower than ketamine 100 mg (89%).
9.3Dependence Physical dependence is characterized by withdrawal symptoms after abrupt discontinuation or a significant dose reduction of a drug. A nonclinical dependence study in rats demonstrated withdrawal symptoms, including hyperreactivity to handling, muscle rigidity, and decreases in food consumption and body weights. Perampanel may cause dependence and withdrawal symptoms that may include anxiety, nervousness, irritability, fatigue, lethargy, asthenia, mood swings, and insomnia.
🔒 Controlled Substance ▾
9.1Controlled Substance Perampanel tablets contain perampanel and are listed as a Schedule III controlled substance.
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, and Impairment of Fertility Carcinogenesis Perampanel was administered orally to mice (1, 3, 10, or 30 mg/kg/day) and rats (10, 30, or 100 mg/kg/day in males; 3, 10, or 30 mg/kg/day in females) for up to 104 weeks. There was no evidence of drug-related tumors in either species. Plasma perampanel exposures (AUC) at the highest doses tested were less than that in humans dosed at 8 mg/day.
Mutagenesis Perampanel was negative in the in vitro Ames and mouse lymphoma tk assays, and in the in vivo rat micronucleus assay. Impairment of Fertility In male and female rats administered perampanel (oral doses of 1, 10, or 30 mg/kg/day) prior to and throughout mating and continuing in females to gestation day 6, there were no clear effects on fertility. Prolonged and/or irregular estrus cycles were observed at all doses but particularly at the highest dose tested.
Plasma perampanel exposures (AUC) at all doses were lower than that in humans dosed at 8 mg/day.
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, and Impairment of Fertility Carcinogenesis Perampanel was administered orally to mice (1, 3, 10, or 30 mg/kg/day) and rats (10, 30, or 100 mg/kg/day in males; 3, 10, or 30 mg/kg/day in females) for up to 104 weeks. There was no evidence of drug-related tumors in either species. Plasma perampanel exposures (AUC) at the highest doses tested were less than that in humans dosed at 8 mg/day.
Mutagenesis Perampanel was negative in the in vitro Ames and mouse lymphoma tk assays, and in the in vivo rat micronucleus assay. Impairment of Fertility In male and female rats administered perampanel (oral doses of 1, 10, or 30 mg/kg/day) prior to and throughout mating and continuing in females to gestation day 6, there were no clear effects on fertility. Prolonged and/or irregular estrus cycles were observed at all doses but particularly at the highest dose tested.
Plasma perampanel exposures (AUC) at all doses were lower than that in humans dosed at 8 mg/day.
📄 Package Label / Principal Display Panel ▾
Package/Label Display Panel NDC 0480-7062-56 CIII Perampanel Tablets 2 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 30 Tablets 2
Package/Label Display Panel NDC 0480-7063-56 CIII Perampanel Tablets 4 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 30 Tablets 4
Package/Label Display Panel NDC 0480-7065-56 CIII Perampanel Tablets 6 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 30 Tablets 6
Package/Label Display Panel NDC 0480-7066-56 CIII Perampanel Tablets 8 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 30 Tablets 8
Package/Label Display Panel NDC 0480-7067-56 CIII Perampanel Tablets 10 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 30 Tablets 10
Package/Label Display Panel NDC 0480-7068-56 CIII Perampanel Tablets 12 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 30 Tablets 12