Perampanel
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Perampanel: From Partial Epilepsy to Visual Epilepsy
One-Sentence Summary
Perampanel is an antiseizure medication that blocks AMPA glutamate receptors. It was originally used for partial-onset (focal) epilepsy. The TxGNN model predicts it may be effective for visual epilepsy (seizures triggered by visual stimuli), but the supporting evidence is thin: 0 clinical trials and 19 publications, none of which studies visual epilepsy directly.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Partial epilepsy; partial motor epilepsy |
| Predicted New Indication | Visual epilepsy |
| TxGNN Prediction Score | 99.92% |
| Evidence Level | L4 |
| US Market Status | Cancelled only (no currently valid authorization) |
| Number of NDAs | 5 authorizations in total (2 NDAs, 3 ANDAs), all cancelled |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data was not available in the data compiled for this report. The literature does describe perampanel as a selective, noncompetitive AMPA-receptor antagonist. It reduces excitation at postsynaptic membranes, and its efficacy in focal-onset seizures is established.
Visual epilepsy (photosensitive or visually triggered seizures) plausibly shares the glutamatergic hyperexcitability that perampanel dampens in focal epilepsy. Preclinical work in other reflex-seizure models supports this idea. For example, perampanel reduced audiogenic seizures in genetically epilepsy-prone rats.
However, none of the retrieved studies addresses visual epilepsy. The literature consists of general epilepsy reviews, guidelines, and cohort studies, so the support is indirect. The high TxGNN score is a computational signal, not clinical proof.
Clinical Trial Evidence
Currently no related clinical trials registered for visual epilepsy.
Literature Evidence
None of the publications below studies visual epilepsy specifically. They show perampanel’s general antiseizure profile. No randomized controlled trials were found.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37059702 | 2023 | Cochrane review | Cochrane Database Syst Rev | Perampanel as add-on therapy for drug-resistant focal epilepsy |
| 35061214 | 2022 | Systematic review / network meta-analysis | Drugs | Indirect comparison of perampanel and four other third-generation antiseizure drugs as adjunctive therapy for focal-onset seizures |
| 37378757 | 2023 | Systematic review / network meta-analysis | J Neurol | Efficacy and safety of antiseizure medications in idiopathic generalized epilepsies |
| 29898971 | 2018 | Guideline update | Neurology | AAN/AES guidance on newer antiepileptic drugs for new-onset epilepsy |
| 36150304 | 2022 | Review | Epilepsy Behav | Perampanel monotherapy: clinical trial and real-world evidence; US-approved for focal-onset seizures and adjunctive treatment of generalized tonic-clonic seizures |
| 29953584 | 2019 | Narrative review | Epilepsia | Evaluates perampanel’s potential as a broad-spectrum antiseizure drug across preclinical and clinical data |
| 36734057 | 2023 | Review / cohort | Epilepsia | Perampanel as precision therapy in rare genetic epilepsies with glutamate-receptor overactivation |
| 36034267 | 2022 | Cohort | Front Neurol | Real-life effectiveness and tolerability of perampanel in childhood absence epilepsy |
| 24559052 | 2014 | Review | Expert Opin Drug Discov | Discovery and development of perampanel, the first approved drug to inhibit postsynaptic excitation via AMPA receptors |
| 41043235 | 2025 | Prospective multicenter study | Epilepsy Behav | Effects of perampanel on seizures and sleep quality in people with epilepsy |
US Market Information
All five US authorizations are cancelled. Indication text was not available for them.
| Authorization Number | Product Name | Dosage Form | Manufacturer | Status |
|---|---|---|---|---|
| NDA202834 | Fycompa | Tablet | Eisai Inc. | Cancelled |
| NDA208277 | Fycompa | Suspension | Eisai Inc. | Cancelled |
| ANDA209801 | Perampanel | Film-coated tablet | Teva Pharmaceuticals, Inc. | Cancelled |
| ANDA209538 | Perampanel | Film-coated tablet | Sun Pharmaceutical Industries, Inc. | Cancelled |
| ANDA218178 | Perampanel | Film-coated tablet | Novadoz Pharmaceuticals LLC | Cancelled |
Safety Considerations
- Drug Interactions: 56 interactions were recorded. The 20 listed in the compiled data are mostly moderate and involve additive central nervous system depression or sedation. They include:
- Opioids: morphine (including liposomal), codeine, hydrocodone, opium, difenoxin, diphenoxylate.
- Cannabinoids: dronabinol, nabilone.
- Other sedating drugs: ethanol, promethazine, chlorpheniramine, azelastine (nasal), metoclopramide.
- Others: dexamethasone, chloroquine, hydroxychloroquine, sibutramine, dextromethorphan.
- Clarithromycin is the one minor interaction.
- Psychiatric and behavioral effects: The literature describes a boxed warning for serious psychiatric and behavioral reactions (aggression, irritability), and rare psychosis has been reported. Irritability is a recognized adverse effect.
Please refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is very high, but no clinical trials exist and no study addresses visual epilepsy directly. The mechanism (AMPA antagonism) is plausible, but the evidence is indirect (L4). The drug also has no currently valid US authorization.
To proceed, the following is needed:
- Case reports, case series, or an EEG-based study of perampanel in photosensitive or visually triggered epilepsy, or a preclinical photosensitivity model.
- Mechanism-of-action data and package insert warnings and contraindications.
- A safety plan for the psychiatric and behavioral risks and for CNS-depressant interactions.
- A decision on a regulatory pathway, given that all US authorizations are cancelled.
Note on other predictions: Among the other top-ranked predictions, status epilepticus has the strongest support (L3). It has a recruiting Phase 2 trial (NCT06401707), a completed retrospective cohort, and several systematic reviews. It may be a better near-term repurposing candidate than visual epilepsy.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.