Perampanel
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
- Perampanel
- Perampanel: From Partial Epilepsy to Visual Epilepsy
Perampanel: From Partial Epilepsy to Visual Epilepsy
One-Sentence Summary
Perampanel is an antiseizure medicine, originally used for partial (focal-onset) epilepsy. The TxGNN model predicts it may be effective for visual epilepsy, but no clinical trials and no studies specific to this condition were found. The 19 publications retrieved are general epilepsy literature, so support is indirect.
Among the other predicted indications, status epilepticus has the strongest evidence (4 clinical trials and 19 publications). It is covered in the supplementary section below.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Partial epilepsy; partial motor epilepsy (the Singapore licence records contain no indication text) |
| Predicted New Indication | Visual epilepsy |
| TxGNN Prediction Score | 99.92% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 4 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. From the literature, perampanel is a selective, non-competitive AMPA-type glutamate receptor antagonist. It reduces glutamate-mediated excitation at postsynaptic membranes and is approved as add-on therapy for focal-onset seizures.
Visual (visually triggered) epilepsy is a reflex epilepsy and may share the glutamatergic hyperexcitability seen in focal epilepsy. This is the mechanistic basis for the prediction. However, none of the retrieved papers study visually triggered seizures. They are general epilepsy reviews, guidelines and perampanel studies, so the link is plausible but unproven.
Clinical Trial Evidence
Currently no related clinical trials registered for visual epilepsy.
Literature Evidence
None of the retrieved publications is specific to visual epilepsy. The most relevant general evidence is below.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 35061214 | 2022 | Systematic review / network meta-analysis | Drugs | Compares third-generation antiseizure medicines, including perampanel, as add-on therapy for focal-onset seizures in adults |
| 37378757 | 2023 | Systematic review / network meta-analysis | J Neurol | Efficacy and safety of antiseizure medicines in idiopathic generalized epilepsies |
| 37059702 | 2023 | Cochrane review | Cochrane Database Syst Rev | Perampanel add-on for drug-resistant focal epilepsy |
| 29898971 | 2018 | Guideline | Neurology | AAN/AES guideline update on newer antiepileptic drugs in new-onset epilepsy |
| 36150304 | 2022 | Review | Epilepsy Behav | Clinical trial and real-world evidence for perampanel monotherapy |
| 29953584 | 2019 | Review | Epilepsia | Discusses perampanel's broad-spectrum potential |
| 24559052 | 2014 | Review | Expert Opin Drug Discov | Discovery and development of perampanel as an AMPA antagonist |
| 36734057 | 2023 | Cohort/review | Epilepsia | Perampanel as precision therapy in rare genetic epilepsies |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14616P | FYCOMPA Film-Coated Tablet 2 mg | Tablet, film coated | Not stated in the available record |
| SIN14617P | FYCOMPA Film-Coated Tablet 4 mg | Tablet, film coated | Not stated in the available record |
| SIN14619P | FYCOMPA Film-Coated Tablet 8 mg | Tablet, film coated | Not stated in the available record |
| SIN16512P | FYCOMPA Oral Suspension 0.5 mg/ml | Suspension | Not stated in the available record |
Safety Considerations
- Drug Interactions: 56 interactions were recorded. Most are moderate, and most involve central nervous system depressants or other sedating drugs. Examples:
- Opioids: morphine, codeine, hydrocodone, opium, diphenoxylate, difenoxin
- Cannabinoids: dronabinol, nabilone
- Sedating antihistamines and others: promethazine, chlorpheniramine
- Other: ethanol, dexamethasone, metoclopramide, chloroquine, hydroxychloroquine, dextromethorphan, sibutramine
- Clarithromycin is the only minor interaction listed in the examples.
- Literature safety signals: Case reports describe psychosis and irritability with perampanel. One report notes a boxed warning for serious psychiatric and behavioural reactions, and another describes food aversion.
Please refer to the package insert for warnings and contraindications.
Supplementary: Other Predicted Indications
| Predicted Indication | Score | Evidence Level | Notes |
|---|---|---|---|
| Status epilepticus | 99.77% | L2 | 4 trials, 19 publications; most promising |
| Audiogenic seizures | 99.86% | L4 | Animal models only (DBA/2 mice, genetically epilepsy-prone rats) |
| Reading seizures | 99.83% | L4 | Indirect literature only |
| Eating seizures | 99.86% | L4 | Case reports only, one describing an adverse effect |
| Thinking seizures | 99.86% | L4 | Indirect literature only |
| Micturition-induced seizures | 99.86% | L4 | Indirect literature only |
| Orgasm-induced seizures | 99.86% | L5 | Prediction only |
| Startle epilepsy | 99.86% | L5 | Prediction only |
| Beta-ketothiolase deficiency | 99.79% | L5 | Prediction only; no clear mechanistic link |
Status Epilepticus: Clinical Trials
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT06401707 | Phase 2 | Recruiting | 52 | Placebo-controlled pilot of perampanel for status epilepticus prophylaxis after cardiac arrest; no results yet |
| NCT04309721 | Phase 3 | Terminated | 1 | Add-on perampanel in focal motor status epilepticus; terminated, no usable data |
| NCT05684978 | Phase 4 | Terminated | 1 | Perampanel in refractory status epilepticus; terminated, no usable data |
| NCT05756621 | N/A | Completed | 84 | Retrospective cohort of ketamine plus perampanel in super-refractory status epilepticus after cardiac arrest |
Status Epilepticus: Literature
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 35151187 | 2022 | Systematic review | Epilepsy Behav | Assesses perampanel efficacy and safety in SE, refractory SE and super-refractory SE |
| 30613951 | 2019 | Retrospective cohort | Acta Neurol Scand | Multinational cases of perampanel in established, refractory and super-refractory SE |
| 38761446 | 2024 | Cohort / case series | Epilepsy Behav | Oral suspension in refractory and super-refractory SE; dose and safety |
| 38256862 | 2023 | Case series | Pharmaceuticals | Perampanel in refractory SE with suspected inflammatory cause |
| 30891695 | 2019 | Cohort | Neurocrit Care | Perampanel for refractory SE in a neurological ICU |
| 29663350 | 2018 | Mechanistic review | Epilepsia | Role of AMPA receptors and antagonists in SE |
Conclusion and Next Steps
Decision: Hold (for the primary prediction, visual epilepsy)
Rationale: The prediction score is high, but there are no clinical trials and no literature specific to visual epilepsy. Support rests on the shared AMPA-mediated mechanism and general epilepsy data (L4). Safety and labelling data are also incomplete.
To proceed, the following is needed:
- Case series or trials specific to visual (photosensitive) epilepsy
- Package insert warnings and contraindications from the Singapore regulator, plus the approved indication text
- Mechanism of action data from DrugBank
- Monitoring of psychiatric adverse effects, and a review of interactions with sedating drugs
- Separate evaluation of status epilepticus, the best-supported alternative. It could move forward as a research question once results from the recruiting Phase 2 trial (NCT06401707) are available.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.