# Perampanel
**Perampanel** (brand name Fycompa; code name E2007) is an orally active, non-competitive, and selective antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of the glutamate receptor, used as an antiseizure medication for epilepsy.[1](https://www.cancer.gov/publications/dictionaries/cancer-drug/def/perampanel) It was the first AMPA glutamate receptor antagonist approved for any indication, receiving United States approval on October 22, 2012 under the trade name Fycompa.[2](https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208277Orig1s000OtherR.pdf) It is indicated for partial-onset seizures with or without secondarily generalized seizures and, as adjunctive therapy, for primary generalized tonic-clonic (PGTC) seizures.[3](https://www.drugs.com/history/fycompa.html)
| Key fact | Detail |
|---|---|
| Drug class | Non-competitive, selective AMPA glutamate receptor antagonist; ATC code N03AX22[1](https://www.cancer.gov/publications/dictionaries/cancer-drug/def/perampanel) • [4](https://precision.fda.gov/ginas/app/ui/browse-substance?search=root_codes_comments%3A%22Noncompetitive+AMPA+Glutamate+Receptor+Antagonist+%5BEPC%5D%22) |
| First approvals | EU marketing authorization 23 July 2012; US FDA approval 22 October 2012 for partial-onset seizures in patients 12 years and older[2](https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208277Orig1s000OtherR.pdf) • [5](https://www.ema.europa.eu/en/medicines/human/EPAR/fycompa) |
| Later indications | Adjunctive PGTC seizures (June 2015); oral suspension (May 2016); monotherapy for partial-onset seizures (July 2017); pediatric patients as young as 4 years (September 2018)[3](https://www.drugs.com/history/fycompa.html) |
| Dosing | 2 mg once daily at bedtime, increased by 2 mg increments at weekly intervals; maintenance 8 to 12 mg once daily for partial-onset seizures, 8 mg for PGTC seizures[6](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=bc8f7cf2-c19c-4235-859f-9ff1dd21908e) |
| Half-life | Approximately 105 hours, falling to about 24 hours in the presence of enzyme-inducing antiepileptic drugs; 95% protein bound[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC3854741/) |
| Controlled-substance status | US DEA Schedule III (final ruling 2 December 2013)[2](https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208277Orig1s000OtherR.pdf) |
| Most common adverse effects | Dizziness and somnolence, seen in more than 1 patient in 10[5](https://www.ema.europa.eu/en/medicines/human/EPAR/fycompa) |
## Mechanism of action
Perampanel is a non-competitive antagonist at the ionotropic AMPA glutamate receptor on postsynaptic neurons.[1](https://www.cancer.gov/publications/dictionaries/cancer-drug/def/perampanel) [In vitro](https://www.edgepedia.org/in-vitro), it did not compete with AMPA for receptor binding, but its binding was displaced by noncompetitive [AMPA receptor](https://www.edgepedia.org/ampa-receptor) antagonists, supporting its classification as a noncompetitive antagonist.[8](https://www.ema.europa.eu/en/documents/product-information/fycompa-epar-product-information_en.pdf) Glutamate is the primary excitatory neurotransmitter in the central nervous system and can trigger and maintain seizures; by blocking AMPA receptor activation, perampanel inhibits neuronal excitation, repetitive neuronal firing, and stabilizes hyper-excited neural membranes.[1](https://www.cancer.gov/publications/dictionaries/cancer-drug/def/perampanel) • [5](https://www.ema.europa.eu/en/medicines/human/EPAR/fycompa)
The precise mechanism by which perampanel exerts its antiepileptic effects in humans is unknown, a statement that appears in both the FDA label and the European product information.[6](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=bc8f7cf2-c19c-4235-859f-9ff1dd21908e) • [8](https://www.ema.europa.eu/en/documents/product-information/fycompa-epar-product-information_en.pdf) Studies suggest that AMPA receptor antagonism can reduce overstimulation, produce anticonvulsant effects, inhibit seizure generation and spread, and may prevent neuronal death.[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC5083075/)
## Pharmacokinetics and dosing
Administration produces rapid and complete absorption with negligible first-pass metabolism; the median time to peak concentration is 0.5 to 2.5 hours when fasting, delayed by two to three hours when taken with food.[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC5083075/) The drug is 95% protein bound, and its long half-life of approximately 105 hours permits once-daily bedtime dosing, which alleviates its most common adverse event of postdose sedation.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC3854741/) In the presence of enzyme-inducing antiepileptic drugs, the half-life falls to about 24 hours.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC3854741/)
The recommended starting dosage in adults and pediatric patients 4 years and older is 2 mg once daily at bedtime, increased no more frequently than weekly in 2 mg increments. The maintenance dose is 8 to 12 mg once daily for partial-onset seizures (monotherapy or adjunctive) and 8 mg once daily for adjunctive treatment of PGTC seizures.[6](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=bc8f7cf2-c19c-4235-859f-9ff1dd21908e) Moderate and strong CYP3A4 inducers, including the antiepileptic drugs carbamazepine, oxcarbazepine, and phenytoin, increase clearance and reduce perampanel plasma concentrations, so dose adjustment is recommended with these drugs.[6](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=bc8f7cf2-c19c-4235-859f-9ff1dd21908e) Maximum recommended daily doses are lower in hepatic impairment (6 mg for mild, 4 mg for moderate impairment), and the drug is not recommended in severe hepatic impairment, severe renal impairment, or hemodialysis.[6](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=bc8f7cf2-c19c-4235-859f-9ff1dd21908e)
## Regulatory history
The European Union approved perampanel on July 23, 2012, and the FDA approved it on October 22, 2012 as adjunctive therapy for partial-onset seizures with or without secondarily generalized seizures in patients 12 years of age and older.[2](https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208277Orig1s000OtherR.pdf) On December 2, 2013, the US Drug Enforcement Agency placed perampanel under Schedule III of the [Controlled Substances Act](https://www.edgepedia.org/controlled-substances-act), and the drug became commercially available in the US on January 2, 2014.[2](https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208277Orig1s000OtherR.pdf)
Subsequent FDA actions extended the label: adjunctive treatment of PGTC seizures (June 2015), an oral suspension (May 2016), monotherapy for partial-onset seizures (July 2017), and treatment of partial-onset seizures in pediatric patients as young as 4 years old (September 2018).[3](https://www.drugs.com/history/fycompa.html) The FDA also granted perampanel orphan drug designation on 12 July 2012 for treatment of Lennox-Gastaut syndrome, without approval for that condition.[10](https://ptacts.uspto.gov/ptacts/public-informations/petitions/1462749/download-documents?artifactId=L6sHg9RGykR5guVa0-aZ_-VYUHWhDmeJ-oT6RAfL3m8Vgn3SLzEunb0) From first launch in September 2012 through late 2015, cumulative worldwide exposure was estimated at approximately 6.9 million patient-days.[2](https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208277Orig1s000OtherR.pdf)
## Clinical efficacy
In three primary trials covering 1,491 participants aged 12 or above, Fycompa proved better than a placebo at lowering how often partial seizures occurred.[5](https://www.ema.europa.eu/en/medicines/human/EPAR/fycompa) In a meta-analysis of eight randomized controlled trials, the 50% responder rate and seizure-free rate were significantly higher with perampanel than with placebo, with risk ratios of 1.57 (95% CI 1.35 to 1.82) and 2.79 (95% CI 1.58 to 4.93), respectively; the 50% responder rates for the 8 mg and 12 mg doses were similar.[11](https://pubmed.ncbi.nlm.nih.gov/36206645/) In a meta-analysis of seven double-blind randomized trials in pharmacoresistant focal seizures, risk ratios for 50% responder rates versus placebo were 1.39 (95% CI 1.08 to 1.79) for 4 mg, 1.83 (95% CI 1.51 to 2.22) for 8 mg, and 1.81 (95% CI 1.45 to 2.27) for 12 mg once daily, with tolerability better at lower doses.[12](https://pubmed.ncbi.nlm.nih.gov/35305446/)
**Real-world evidence.** A systematic review of 56 observational studies including 10,688 patients aged 12 and older found pooled 50% responder rates of 50.0% (95% CI 0.41 to 0.60), 44.0% (95% CI 0.38 to 0.50), and 39.0% (95% CI 0.31 to 0.48) after 3, 6, and 12 months of treatment, and pooled seizure-free rates of 24.0%, 21.0%, and 20.0% at the same time points.[13](https://pmc.ncbi.nlm.nih.gov/articles/PMC10086234/) Efficacy was higher when perampanel was used as the first add-on, as primary monotherapy, or combined with non-enzyme-inducing antiepileptic drugs, compared with late add-on, conversion therapy, or combination with enzyme-inducing drugs.[13](https://pmc.ncbi.nlm.nih.gov/articles/PMC10086234/)
**Generalized seizures.** A systematic review of 91 reports examining perampanel in generalized seizures found Class I evidence of efficacy and tolerability as adjunctive therapy for primary generalized tonic-clonic seizures in patients aged 12 and older with idiopathic generalized epilepsy, and weaker observational evidence in myoclonic, absence, and tonic seizures, with no patterns suggesting seizure worsening.[14](https://pmc.ncbi.nlm.nih.gov/articles/PMC8354889/) In a network meta-analysis of 28 randomized trials (4,282 patients) of antiseizure medications for idiopathic generalized epilepsies, perampanel ranked best for safety as measured by any treatment-emergent adverse event, and recent unblinded controlled studies showed it reduced generalized seizures by a median of 90% over 52-week follow-up.[15](https://pubmed.ncbi.nlm.nih.gov/37378757/) • [16](https://pmc.ncbi.nlm.nih.gov/articles/PMC10511599/)
## Safety and tolerability
The most common adverse reactions (5% or more and at least 1% higher than placebo) are dizziness, somnolence, fatigue, irritability, falls, nausea, weight gain, vertigo, ataxia, headache, vomiting, contusion, abdominal pain, and anxiety.[6](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=bc8f7cf2-c19c-4235-859f-9ff1dd21908e) A pooled-data review identified dizziness, somnolence, fatigue, irritability, nausea, and falls as the most common adverse drug reactions.[17](https://onlinelibrary.wiley.com/doi/10.1111/epi.12504)
**Boxed warning.** The US label carries a boxed warning for serious or life-threatening psychiatric and behavioral adverse reactions, including aggression, hostility, irritability, anger, and homicidal ideation and threats. In controlled partial-onset seizure trials, hostility- and aggression-related reactions occurred in 12% of patients at 8 mg per day and 20% at 12 mg per day, compared with 6% on placebo; these dose-related effects generally appeared within the first 6 weeks of treatment. Homicidal ideation and/or threat were exhibited in 0.1% of 4,368 perampanel-treated patients across controlled and open-label trials. Patients should be monitored during treatment and for at least 1 month after the last dose, particularly during titration and at higher doses.[6](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=bc8f7cf2-c19c-4235-859f-9ff1dd21908e) In the real-world meta-analysis, the pooled incidence of drug-related psychiatric adverse events was 24% (95% CI 0.15 to 0.33) across nine studies with 4,548 patients, and withdrawal rates due to adverse events were 8.0%, 16.0%, and 16% at 3, 6, and 12 months; rapid titration carried a higher withdrawal rate (30%) than slow titration (12%).[13](https://pmc.ncbi.nlm.nih.gov/articles/PMC10086234/) A meta-analysis of randomized trials found the most-reported treatment-emergent adverse events were dizziness and somnolence, with fewer than 1% of patients reporting serious psychological outcomes.[11](https://pubmed.ncbi.nlm.nih.gov/36206645/)
## References
1. [Perampanel, NCI Drug Dictionary, National Cancer Institute](https://www.cancer.gov/publications/dictionaries/cancer-drug/def/perampanel)
2. [Fycompa (perampanel), NDA 208277, Regulatory History, FDA](https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208277Orig1s000OtherR.pdf)
3. [Fycompa (perampanel) FDA Approval History, Drugs.com](https://www.drugs.com/history/fycompa.html)
4. [GSRS substance browser, Noncompetitive AMPA Glutamate Receptor Antagonist, FDA precisionFDA](https://precision.fda.gov/ginas/app/ui/browse-substance?search=root_codes_comments%3A%22Noncompetitive+AMPA+Glutamate+Receptor+Antagonist+%5BEPC%5D%22)
5. [Fycompa, European Medicines Agency, EPAR overview](https://www.ema.europa.eu/en/medicines/human/EPAR/fycompa)
6. [PERAMPANEL tablet, film coated, DailyMed label, NLM](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=bc8f7cf2-c19c-4235-859f-9ff1dd21908e)
7. [Perampanel: A Selective AMPA Antagonist for Treating Seizures, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC3854741/)
8. [Fycompa, INN-perampanel, EPAR Product Information, EMA](https://www.ema.europa.eu/en/documents/product-information/fycompa-epar-product-information_en.pdf)
9. [Perampanel (Fycompa): A Review of Clinical Efficacy and Safety in Epilepsy, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC5083075/)
10. [Thirty Years of Orphan Drug Legislation and the Development of Drugs to Treat Rare Seizure Conditions](https://ptacts.uspto.gov/ptacts/public-informations/petitions/1462749/download-documents?artifactId=L6sHg9RGykR5guVa0-aZ_-VYUHWhDmeJ-oT6RAfL3m8Vgn3SLzEunb0)
11. [Efficacy and safety of perampanel in epilepsy: A systematic review and meta-analysis of randomised controlled trials, Seizure (PubMed)](https://pubmed.ncbi.nlm.nih.gov/36206645/)
12. [Efficacy, tolerability and safety of perampanel in population with pharmacoresistant focal seizures: A systematic review and meta-analysis (PubMed)](https://pubmed.ncbi.nlm.nih.gov/35305446/)
13. [Efficacy and tolerability of perampanel in patients with seizures in real-world clinical practice: A systematic review and meta-analysis, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC10086234/)
14. [Exploring the Evidence for Broad-Spectrum Effectiveness of Perampanel, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC8354889/)
15. [Antiseizure medications for idiopathic generalized epilepsies: a systematic review and network meta-analysis (PubMed)](https://pubmed.ncbi.nlm.nih.gov/37378757/)
16. [Antiseizure medications for idiopathic generalized epilepsies: a systematic review and network meta-analysis, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC10511599/)
17. [Adverse effects and safety profile of perampanel: A review of pooled data, Epilepsia](https://onlinelibrary.wiley.com/doi/10.1111/epi.12504)
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*Topic: Encyclopedia › Life and health › Human health and medicine › Medicines and therapeutics › Psychiatric and neurological medications › Anticonvulsants and neurological agents › Antiseizure medications*
*Initially written Oct 21, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license