Perampanel

Evidence Level: L5

Predicted Indications: 1

Perampanel

Pharmacist Assessment Report

Perampanel: Beta-ketothiolase deficiency

One-Sentence Summary

Perampanel is an antiseizure medicine (a non-competitive AMPA receptor antagonist) originally used for partial (focal) epilepsy. The TxGNN model predicts it may be effective for beta-ketothiolase deficiency, but there are no registered clinical trials and no publications specific to this condition. The only supporting literature covers focal epilepsy in general, so the evidence is model prediction with indirect support.

Quick Overview

Item	Content
Original Indication	Not recorded in the local data
Predicted New Indication	Beta-ketothiolase deficiency
TxGNN Prediction Score	0.9979
Evidence Level	L5
Australia Market Status	Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data
Number of PBS Items	1 (valid: 1)
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism of action data is not available in the data compiled for this report. Based on the literature, perampanel is a selective, non-competitive AMPA-type glutamate receptor antagonist. It reduces excitatory glutamatergic transmission at postsynaptic membranes, which underlies its use as add-on therapy in focal-onset seizures.

Visual epilepsy (photosensitive or occipital seizures) is a focal or reflex seizure type. It plausibly involves the same AMPA-mediated glutamatergic hyperexcitability as the original indication. However, the retrieved literature addresses drug-resistant focal epilepsy in general, not visual epilepsy specifically. The link is therefore indirect and largely overlaps with the approved use rather than demonstrating a new benefit.

The score for beta-ketothiolase deficiency (0.9979) comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence.

Clinical Trial Evidence

Currently no related clinical trials registered for visual epilepsy.

Trial Number	Phase	Status	Enrolment	Key Findings
NCT06401707	Phase 2	Recruiting	52	Randomised placebo-controlled pilot of perampanel to prevent status epilepticus after cardiac arrest; no results yet
NCT04309721	Phase 3	Terminated	1	Add-on enteral perampanel in focal motor status epilepticus; terminated early, no usable data
NCT05684978	Phase 4	Terminated	1	Perampanel in refractory status epilepticus; terminated early, no interpretable results
NCT05756621	N/A	Completed	84	Retrospective cohort of ketamine plus perampanel in super-refractory status epilepticus after cardiac arrest; contextual data only

Literature Evidence

No publications specific to visual epilepsy were retrieved. The following are the most relevant to perampanel in focal epilepsy, the closest available evidence:

PMID	Year	Type	Journal	Key Findings
37059702	2023	Review (Cochrane)	Cochrane Database Syst Rev	Perampanel add-on therapy in drug-resistant focal epilepsy
35305446	2022	Systematic review / meta-analysis	Epilepsy Res	Efficacy, tolerability and safety of perampanel in pharmacoresistant focal seizures
35061214	2022	Network meta-analysis	Drugs	Indirect comparison of third-generation antiseizure medicines, including perampanel, for focal-onset seizures
35816832	2022	Review	Epilepsy Behav	Scoping review of real-world perampanel effectiveness and safety in Europe
36263757	2022	Cohort / review	Expert Opin Drug Saf	Safety of perampanel as monotherapy or first add-on therapy
40839459	2025	Observational cohort	Epilepsia Open	PERPRISE: real-world effectiveness of perampanel as the only add-on therapy in Germany
24559052	2014	Review	Expert Opin Drug Discov	Discovery and development of perampanel as an AMPA antagonist

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
10151G	Fycompa	Tablet 10 mg (as hemisesquihydrate), oral	Not available in the data compiled for this report

Safety Considerations

Drug Interactions: 56 interactions were identified. The listed ones are mostly moderate, and chiefly involve additive central nervous system depression or sedation. Examples include morphine, codeine, hydrocodone, opium, diphenoxylate, difenoxin, dronabinol, nabilone, promethazine, chlorpheniramine, metoclopramide, dextromethorphan, ethanol, and dexamethasone. Chloroquine, hydroxychloroquine and sibutramine are also listed as moderate. Clarithromycin is listed as minor.
Literature safety signals: The retrieved publications report psychiatric adverse effects (irritability, psychosis) and food aversion. One publication notes a boxed warning for serious psychiatric and behavioural reactions. These come from case reports and a literature review, not from Australian label text.

Please refer to the TGA-approved Product Information (PI) for the full warnings and contraindications, which were not available in the data compiled for this report.

Conclusion and Next Steps

Decision: Hold

Rationale: The high prediction score for beta-ketothiolase deficiency rests on a general anti-glutamatergic mechanism. There are no trials and no disease-specific publications. The literature largely restates the existing focal epilepsy indication, so it does not independently support a new use.

To proceed, the following is needed:

Disease-specific evidence, such as case series, preclinical photosensitivity models, or a pilot study in visual or photosensitive epilepsy
Clarification of whether visual epilepsy is already covered by the approved focal-seizure indication
The approved indication text and safety sections (warnings, contraindications) from the Australian PI
Mechanism of action data confirmed from a primary source
For a better-supported direction, consider status epilepticus (evidence level L3), pending results from ongoing and future trials, since the completed trials were terminated with one participant each
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.