We review our content at regular intervals and update it whenever new research or a change in clinical guidelines requires it.
| FIELD OF APPLICATION | DETAILS |
|---|---|
| Generic Name | Perampanel |
| Active Ingredient | Perampanel hydrate |
| Brand Names | Fycompa, Taro-perampanel |
| Drug Category | Neurology |
| Drug Class | Adjunct therapy, Palliative treatment, Immunosuppressive therapy, Targeted therapy |
| Dosage Forms | Kit, Suspension, Tablet, Tablet, coated, Tablet, film coated |
| Route of Administration | Oral |
| FDA Approval Status | FDA Approved (October 2012) Approved |
Perampanel: Overview
Perampanel is an antiepileptic medication that belongs to the class of organic compounds known as bipyridines and oligopyridines, characterized by two linked pyridine rings. It serves as a first-in-class, non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist. The medication is used both as a monotherapy and as an adjunctive treatment to control partial-onset seizures and primary generalized tonic-clonic seizures in patients with epilepsy.
What Is Perampanel & How Does It Work?
Perampanel is classified chemically as a bipyridine derivative featuring a complex heterotricyclic framework. It is a small-molecule central nervous system depressant designed to target post-synaptic glutamate signaling pathways.
The primary mechanism of action of perampanel involves the non-competitive inhibition of post-synaptic AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) ionotropic glutamate receptors. Glutamate is the principal excitatory neurotransmitter in the human central nervous system, and overactivation of AMPA receptors leads to excessive neuronal excitation and seizure activity. By binding selectively as an antagonist to AMPA receptors (specifically glutamate receptor 1, 2, 3, and 4 subunits), perampanel blocks glutamate-mediated post-synaptic excitation, thereby reducing hyper-synchronous neuronal firing and suppressing seizure activity.
Is Perampanel FDA Approved?
Perampanel is FDA Approved. It received its initial approval from the U.S. Food and Drug Administration in October 2012 under the trade name Fycompa.
The drug is indicated for the treatment of partial-onset seizures (with or without secondarily generalized seizures) in epileptic patients 4 years of age and older. Additionally, it is FDA approved as an adjunctive treatment for primary generalized tonic-clonic (PGTC) seizures in patients aged 12 years and older.
What Is Perampanel Used For?
Perampanel is indicated for managing specific seizure types in pediatric and adult epilepsy populations.
- Partial-Onset Seizures: Indicated as monotherapy or adjunctive therapy for the treatment of partial-onset seizures with or without secondarily generalized seizures in patients 4 years of age and older .
- Primary Generalized Tonic-Clonic (PGTC) Seizures: Indicated as an adjunctive treatment for primary generalized tonic-clonic seizures in epileptic patients aged 12 years and older .
Before Taking Perampanel: Contraindications & Precautions
Clinicians must perform a thorough psychiatric and neurological risk assessment before prescribing perampanel. Due to its profound effects on central neurotransmission, specific precautions are mandatory.
Who Should Not Take Perampanel?
Perampanel is contraindicated in patients with a documented hypersensitivity to perampanel or any excipients in the oral tablets or suspension. It is not recommended in patients with severe hepatic impairment or severe renal impairment/end-stage renal disease on hemodialysis due to altered drug clearance.
Perampanel: Pregnancy & Fertility
Data regarding the use of perampanel in pregnant women are limited. Animal reproduction studies have shown developmental toxicity at clinically relevant doses. It should be used during pregnancy only if the potential maternal benefit outweighs the potential fetal risk. Women of childbearing potential should be aware that perampanel may decrease the efficacy of hormonal contraceptives containing levonorgestrel.
Tell Your Doctor Before Taking Perampanel
Inform your healthcare provider if you have a history of depression, mood disorders, violent behavior, suicidal ideation, or substance abuse. Disclose all concurrent medications, particularly liver enzyme-inducing antiepileptic drugs (such as carbamazepine, oxcarbazepine, or phenytoin) and oral contraceptives.
Perampanel: Dosage & Administration
Dosing protocols for perampanel require gradual titration to achieve therapeutic effect while minimizing central nervous system adverse events.
Standard Perampanel Dosing
For partial-onset seizures or primary generalized tonic-clonic seizures, the recommended starting oral dose in adults and adolescents is 2 mg once daily at bedtime. The dosage may be titrated by increments of 2 mg daily no more frequently than weekly intervals based on clinical response and tolerability, up to a target dose of 8 mg to 12 mg once daily at bedtime. When co-administered with strong CYP3A4-inducing antiepileptic drugs, higher starting doses or faster titration schedules may be necessary.
How Perampanel Is Administered
Perampanel is administered orally once daily at bedtime. Film-coated tablets should be swallowed whole with water and should not be chewed or crushed. Oral suspension formulations must be shaken thoroughly before each dose using the provided calibrated oral syringe.
Perampanel: Clinical Efficacy & Research
Randomized, double-blind, placebo-controlled clinical trials have confirmed the clinical efficacy of perampanel in reducing seizure frequency. Studies in patients with refractory partial-onset seizures demonstrated that once-daily bedtime administration of 8 mg or 12 mg perampanel significantly increased 50% responder rates and decreased median seizure frequency compared to placebo. Similarly, in trials evaluating primary generalized tonic-clonic seizures, adjunctive perampanel resulted in a marked reduction in PGTC seizure frequency and a higher proportion of seizure-free patients during the maintenance phase.
Perampanel: Side Effects & Safety Profile
Perampanel carries an FDA Black Box Warning for serious or life-threatening psychiatric and behavioral reactions. These reactions include hostility, aggression, agitation, anger, homicidal ideation, and severe mood changes, which can occur in patients with or without a prior psychiatric history.
Perampanel carries significant warnings regarding central nervous system depression and severe behavioral alterations.
Common Perampanel Side Effects
Common adverse reactions include dizziness, somnolence, fatigue, irritability, gait disturbance (ataxia), vertigo, weight gain, and nausea.
Serious Perampanel Adverse Events
Serious adverse events include severe psychiatric reactions (aggression and homicidal ideation), severe falls secondary to dizziness and gait impairment, drug reaction with eosinophilia and systemic symptoms (DRESS), and suicidal behavior.
Managing Perampanel Side Effects
Patients and caregivers must continuously monitor for changes in mood, anger, or aggressive behavior. If severe psychiatric symptoms develop, clinicians should immediately evaluate the patient and consider dose reduction or gradual discontinuation under close supervision.
Perampanel: Interactions & What to Avoid
Perampanel undergoes extensive hepatic metabolism, making its plasma concentrations sensitive to cytochrome P450 activity.
Perampanel: Interactions
Perampanel is a substrate of CYP3A4, CYP3A5, and CYP1A2 enzymes. Strong CYP3A4 inducers (such as carbamazepine, phenytoin, and oxcarbazepine) significantly increase perampanel clearance, reducing its blood levels by up to 50%. Strong CYP3A4 inhibitors (such as ketoconazole or itraconazole) increase perampanel exposure and prolong its elimination half-life. Additionally, high-dose perampanel (12 mg daily) decreases the exposure of levonorgestrel-containing hormonal contraceptives, which may reduce contraceptive efficacy.
Perampanel: Food & Alcohol
Perampanel can be taken with or without food, though taking it with a high-fat meal slightly delays absorption without altering total exposure. Alcohol consumption must be strictly avoided, as alcohol synergistically increases central nervous system depression and significantly worsens anger, confusion, and motor impairment.
Perampanel: Missed Dose, Overdose & Storage
Proper handling and adherence to bedtime dosing schedules maintain consistent anticonvulsant cover.
Missed Dose of Perampanel
If a single dose is missed, take the missed dose at bedtime the following day. Do not take a double dose to make up for a missed application. If multiple consecutive doses are missed, consult your physician to determine if re-titration from a lower starting dose is necessary.
Perampanel: Overdose & Emergency
An overdose of perampanel causes severe central nervous system depression, altered mental status, severe confusion, gait ataxia, respiratory depression, and potential coma. Emergency management involves immediate supportive care, airway protection, cardiac monitoring, and contact with a Poison Control Center.
How to Store Perampanel
Store oral tablets and oral suspension at controlled room temperature between 20°C and 25°C (68°F to 77°F). Do not freeze the oral suspension, and discard any unused oral suspension 90 days after opening the bottle.
Perampanel: Patient Management & Monitoring
Clinical vigilance ensures that seizure reduction is achieved without compromising patient safety or psychiatric stability.
Tests Before Starting Perampanel
Prior to initiating perampanel, healthcare providers should obtain baseline liver function tests, renal function panels, and evaluate psychiatric history.
Monitoring During Perampanel Treatment
Routine monitoring includes tracking seizure frequency, evaluating cognitive and motor side effects (such as dizziness and gait disturbance), and checking for signs of emerging depression or aggressive behavior.
Perampanel: Do’s and Don’ts
Do take your dose once daily at bedtime to minimize daytime somnolence and dizziness. Don’t consume alcohol or abruptly stop taking perampanel, as rapid withdrawal can trigger rebound seizures.
Frequently Asked Questions
What is Perampanel used for?
Perampanel is an antiepileptic drug used to treat partial-onset seizures in patients 4 years and older and primary generalized tonic-clonic seizures in patients 12 years and older.
Is Perampanel FDA approved?
Yes, Perampanel was FDA approved in October 2012.
How does Perampanel work in epilepsy?
It acts as a non-competitive AMPA glutamate receptor antagonist, blocking excitatory post-synaptic signals to reduce excessive brain activity.
Does Perampanel have an FDA Black Box Warning?
Yes, the FDA label includes an important black-boxed warning of serious or life-threatening behavioral and psychiatric reactions.
What brand name is Perampanel sold under?
Perampanel is marketed under the brand names Fycompa and Taro-perampanel.
What chemical class does Perampanel belong to?
It belongs to the class of organic compounds known as bipyridines and oligopyridines, which contain two pyridine rings linked to each other.
What are the available dosage forms for Perampanel?
Perampanel is available as an oral suspension, various film-coated tablets, standard tablets, and as a combination kit.
References
- DrugBank Online. Perampanel (DB08883).
- U.S. Food and Drug Administration (FDA). Fycompa (perampanel) Prescribing Information.
- National Center for Biotechnology Information (NCBI). PubChem Compound Summary: Perampanel.
Legal Disclaimer
The information provided is for educational and informational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider at any hospital or any local clinic before starting or stopping any medication.
