Perampanel

Evidence Level: L5

Predicted Indications: 1

Perampanel

Pharmacist Assessment Report

Perampanel: Beta-ketothiolase deficiency

One-Sentence Summary

Perampanel is an AMPA-receptor antagonist originally used to treat partial (focal) epilepsy.

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
India Market Status	Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data
Number of Listed Products	at least 20
Recommended Decision	Hold

Why is This Prediction Reasonable?

Perampanel is a non-competitive AMPA-receptor antagonist. It reduces glutamate-mediated excitation at postsynaptic membranes and is approved for focal-onset seizures. Detailed mechanism-of-action data were not available in the data compiled for this report, but the literature consistently describes this mechanism.

Visual (photosensitive or visually triggered) epilepsy is a reflex seizure type, and these seizures are plausibly driven by cortical hyperexcitability. This gives a mechanistic reason to expect benefit. Preclinical studies also show perampanel suppresses audiogenic seizures in reflex-epilepsy rodent models.

It is not disease-specific evidence. The retrieved literature covers general epilepsy topics (guidelines, network meta-analyses, pregnancy, status epilepticus) and nothing on visually induced seizures.

Clinical Trial Evidence

Currently no related clinical trials are registered for visual epilepsy.

Trial Number	Phase	Status	Enrollment	Key Findings
NCT06401707	Phase 2	Recruiting	52	Randomized placebo-controlled pilot of perampanel to prevent status epilepticus after cardiac arrest; results not yet available
NCT04309721	Phase 3	Terminated	1	Add-on enteral perampanel in focal motor status epilepticus; stopped after 1 participant, no usable efficacy data
NCT05684978	Phase 4	Terminated	1	Perampanel in refractory status epilepticus; stopped after 1 participant, no efficacy conclusions possible
NCT05756621	N/A	Completed	84	Retrospective cohort of ketamine plus perampanel in super-refractory status epilepticus after cardiac arrest; perampanel is not clearly the studied intervention

Literature Evidence

No literature specific to visual epilepsy was found. The table below lists the most relevant retrieved items, which are general epilepsy publications.

PMID	Year	Type	Journal	Key Findings
37059702	2023	Systematic review	Cochrane Database Syst Rev	Perampanel as add-on therapy for drug-resistant focal epilepsy
35061214	2022	Network meta-analysis	Drugs	Third-generation antiseizure medications (including perampanel) as adjunctive treatment of focal-onset seizures; no direct head-to-head RCTs
37378757	2023	Network meta-analysis	J Neurol	Comparison of antiseizure medications in idiopathic generalized epilepsies
29898971	2018	Guideline	Neurology	AAN/AES guideline update on new antiepileptic drugs for new-onset epilepsy
36150304	2022	Review	Epilepsy Behav	Perampanel monotherapy: clinical trial and real-world evidence
24559052	2014	Review	Expert Opin Drug Discov	Discovery and development of perampanel as an AMPA antagonist
36734057	2023	Cohort	Epilepsia	Perampanel as precision therapy in rare genetic epilepsies
36218253	2022	Review	Rev Neurol	Paediatric status epilepticus

For status epilepticus, two systematic reviews (35151187, 2022; 30076046, 2018) suggest perampanel may help terminate refractory status epilepticus, based mainly on case series and observational reports.

India Market Information

Authorization Number	Product Name	Dosage Form	Approved Indication
84557	Fycompa 4mg Tablet (Eisai)	Packet of 28 tablets	Not specified
84771	Fycompa 4mg Tablet (Eisai)	Strip of 14 tablets	Not specified
85147	Fycompa 6mg Tablet (Eisai)	Strip of 14 tablets	Not specified
715	Ampanel 4 Tablet (Sun Pharma)	Strip of 10 tablets	Not specified
174795	Perepsy 4 Tablet (Cipla)	Strip of 7 tablets	Not specified

There are 20 valid single-ingredient registrations in total, from manufacturers including Eisai, Sun Pharma, Cipla, Alkem, Torrent, Intas, Hetero and Linux Laboratories.

Safety Considerations

Drug Interactions: 56 interactions were identified. The ones listed below are moderate in severity (clarithromycin is minor):

Opioids and opioid-like agents: morphine, codeine, hydrocodone, opium, diphenoxylate, difenoxin
Cannabinoids: dronabinol, nabilone
Other sedating or CNS-active agents: ethanol, promethazine, chlorpheniramine, dextromethorphan, metoclopramide, sibutramine
Antimalarials: chloroquine, hydroxychloroquine
Corticosteroid: dexamethasone

The literature also notes that perampanel carries a boxed warning for serious psychiatric and behavioral reactions (aggression, irritability), and that psychosis has been reported.

Please refer to the package insert for further safety information.

Conclusion and Next Steps

Decision: Hold

Rationale: There are no trials and no disease-specific literature. Perampanel is already widely marketed in India for epilepsy, so access is not the obstacle; evidence is.

To proceed, the following is needed:

Disease-specific clinical or case data for visually induced or photosensitive seizures
Package insert warnings and contraindications from the Indian labels, along with the approved indication text
Detailed mechanism-of-action data
Consider prioritising status epilepticus (evidence level L3) as a better-supported research question. This depends on results from the recruiting Phase 2 trial (NCT06401707) and further controlled data, since the Phase 3 and Phase 4 studies were terminated after 1 participant each.
Disclaimer

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