Riluzole

Evidence Level: L5

Predicted Indications: 10

Riluzole
1. Pharmacist Assessment Report
Riluzole: From Amyotrophic Lateral Sclerosis to Bilateral Parasagittal Parieto-Occipital Polymicrogyria

Pharmacist Assessment Report

Riluzole: From Amyotrophic Lateral Sclerosis to Bilateral Parasagittal Parieto-Occipital Polymicrogyria

One-Sentence Summary

Riluzole is a drug originally used to treat amyotrophic lateral sclerosis (ALS). The TxGNN model predicts it may be effective for bilateral parasagittal parieto-occipital polymicrogyria, but there are currently 0 clinical trials and 0 publications supporting this specific prediction. It is a model-only prediction.

Quick Overview

Item	Content
Original Indication	Amyotrophic lateral sclerosis
Predicted New Indication	Bilateral parasagittal parieto-occipital polymicrogyria
TxGNN Prediction Score	99.99%
Evidence Level	L5
US Market Status	Cancelled only (all listed authorizations are cancelled)
Number of NDAs	6
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism-of-action data is not available in the data compiled for this report. From general knowledge, riluzole is thought to act by reducing glutamate release and modulating persistent sodium currents. This is the basis for its modest survival benefit in ALS.

Polymicrogyria is a cortical malformation, which is often associated with epilepsy and neurodevelopmental problems. A glutamate-modulating drug could plausibly relate to such conditions, but this link is speculative. No trial or publication in the data directly supports it. The high TxGNN score (99.99%) reflects a knowledge-graph association only and should not be read as clinical evidence.

Other top-ranked predictions are closer to riluzole’s original use, such as lower motor neuron syndrome with late-adult onset, monomelic amyotrophy, Mills syndrome, and genetic ALS subtypes. They are more biologically plausible by analogy to ALS, but they also have no direct trials or literature in the data. Several others, such as axial spondylometaphyseal dysplasia and trichomegaly-retina pigmentary degeneration-dwarfism syndrome, show no identifiable mechanistic link.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

Currently no related literature available for the top-ranked prediction.

For reference, the eighth-ranked prediction, “amyotrophic lateral sclerosis, susceptibility to”, has literature. It overlaps with riluzole’s original indication, so it is not a true repurposing case. Selected records:

PMID	Year	Type	Journal	Key Findings
42161327	2026	Cohort/Association study	Brain	CYP2D6 variants studied in relation to ALS risk and survival. Notes that riluzole’s survival benefit is modest and variable between patients
9178165	1997	Review	J Neurol	Glutamate excitotoxicity hypothesis in ALS, the mechanistic basis for riluzole
21128691	2011	Review	CNS Drugs	ALS pathophysiology and management. Riluzole is the only medication shown to modestly prolong survival
16723044	2006	Review	Expert Rev Mol Med	Proposed ALS mechanisms (oxidative stress, excitotoxicity, mitochondrial dysfunction) and routes to treatment
8061281	1994	Preclinical	Neuroreport	Neuroprotective effects of riluzole against ALS cerebrospinal fluid toxicity in cultured neurons
32040174	2020	Modelling study	Toxicol Sci	DILIsym modelling of liver effects of a sublingual riluzole formulation vs 50 mg oral tablets. About 50% of ALS patients on oral tablets have ALT above the upper limit of normal

These records are indirect evidence. They do not show efficacy for the predicted new indication.

US Market Information

All six authorizations are cancelled. No approved-indication text is available in the data.

Authorization Number	Product Name	Dosage Form	Status
ANDA204048	Riluzole (Ascend Laboratories)	Tablet	Cancelled
ANDA091417	Riluzole (Sun Pharmaceutical)	Tablet, film coated	Cancelled
ANDA091394	Riluzole (Glenmark)	Tablet, film coated	Cancelled
ANDA206045	Riluzole (AvKARE)	Tablet, film coated	Cancelled
NDA209080	TIGLUTIK (EDW Pharma)	Liquid	Cancelled

A sixth entry, Teglutik (EDW Pharma, liquid), is also cancelled and has no valid authorization number.

Safety Considerations

Contraindication-related conditions (from the knowledge graph, not label text): neutropenia, agranulocytosis, substance abuse/dependence, hyperbilirubinemia, hereditary hyperbilirubinemia, Gilbert syndrome, interstitial lung disease, and drug-induced liver injury.
Liver safety: A modelling study reports that about 50% of ALS patients on oral riluzole have ALT above the upper limit of normal, 8% above 3× ULN, and 2% above 5× ULN.
Drug Interactions: 44 interactions were identified. Examples at Moderate level include obeticholic acid, naltrexone, deferasirox, osilodrostat, anagrelide, asparaginase, brentuximab vedotin, clofarabine, methotrexate, and epirubicin. Minor-level examples include omeprazole, caffeine, theophylline, and aminophylline.

Please refer to the package insert for full warnings and contraindications.

Conclusion and Next Steps

Decision: Hold

Rationale: The prediction for bilateral parasagittal parieto-occipital polymicrogyria is supported only by a model score. There are no trials or literature, and the mechanistic link is speculative. All US authorizations are also cancelled. The more plausible candidates are the ALS-related motor neuron conditions, which could be framed as research questions.

To proceed, the following is needed:

Package insert warnings and contraindications (a blocking gap for safety screening)
Detailed mechanism-of-action data
Preclinical or case-level evidence of riluzole’s effect in cortical malformation or epilepsy models
Review of the higher-plausibility ALS-spectrum candidates (lower motor neuron syndrome, monomelic amyotrophy, Mills syndrome) as separate research questions
Clarification of current US availability, since all listed authorizations are cancelled
Disclaimer

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