Clobazam
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Clobazam: From Lennox-Gastaut Syndrome to Febrile Infection-Related Epilepsy Syndrome
One-Sentence Summary
Clobazam is a benzodiazepine antiseizure medication, originally used for Lennox-Gastaut syndrome. The TxGNN model predicts it may be effective for febrile infection-related epilepsy syndrome (FIRES), but there are 0 registered clinical trials and only 2 publications (a case series and a case report, neither studying clobazam directly), so this remains an early research question.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Lennox-Gastaut syndrome (the Singapore licence record contains no indication text) |
| Predicted New Indication | Febrile infection-related epilepsy syndrome |
| TxGNN Prediction Score | 99.82% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not currently available. Based on known information, clobazam is a benzodiazepine that enhances GABA-A receptor signalling. Its efficacy in Lennox-Gastaut syndrome, a severe drug-resistant epilepsy, is established, and mechanistically it may be applicable to FIRES.
FIRES is a refractory epileptic encephalopathy that occurs in previously healthy children after a febrile illness. Seizures are often controlled only with GABAergic agents such as midazolam or barbiturates. This provides a class-level rationale for a GABA-A modulator like clobazam.
The link is indirect, however. The retrieved papers describe enteral lorazepam as a weaning strategy and perampanel for reducing barbiturate dependency. Neither studies clobazam. No clobazam-specific data in FIRES were found.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 35770765 | 2022 | Case series | Epileptic Disorders | Enteral lorazepam was an effective weaning substitute for midazolam-dependent FIRES patients |
| 39958143 | 2025 | Case report | Cureus | Perampanel may reduce barbiturate dependency in a 13-year-old boy with FIRES |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN01591P | FRISIUM 10 TABLET 10 mg (Opella Healthcare International SAS) | Tablet | Indication text not recorded |
Safety Considerations
- Drug Interactions: 100 interactions were identified in the interaction database. The examples reviewed include:
- Major: morphine (including liposomal morphine) and eliglustat.
- Moderate: bupropion, aprepitant, omeprazole, esomeprazole, lansoprazole, cimetidine, clarithromycin, metoclopramide, fenfluramine, dexfenfluramine and dronabinol.
- Minor: antacids such as magnesium oxide, aluminium hydroxide and calcium carbonate.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is very high, but there are no clinical trials and only two small FIRES reports, neither on clobazam. The mechanistic link is class-level and indirect, so the idea is best treated as a research question rather than a candidate for action.
To proceed, the following is needed:
- Clobazam-specific data in FIRES, such as case series or a retrospective cohort
- Detailed mechanism of action data
- Package insert warnings and contraindications from the HSA, which are needed before any safety screening
- A safety plan covering the major interactions, especially with opioids such as morphine, and with additional CNS depressants
Other Predicted Indications (for Reference)
| Rank | Predicted Indication | Score | Evidence Level | Note | |------|------|------|------|------| | 6 | Childhood onset epileptic encephalopathy | 99.59% | L1 | Largely an on-label use (Lennox-Gastaut syndrome), supported by guidelines and reviews. This is not true repurposing, and other encephalopathies (e.g., STXBP1, Angelman, Dravet) need syndrome-specific confirmation. This is the strongest candidate, at Proceed with Guardrails. | | 7 | Benign occipital epilepsy | 99.58% | L4 | A Cochrane review covers clobazam monotherapy in focal or generalized seizures, but nothing is specific to this syndrome. | | 3, 4, 5 | Cryptogenic late-onset epileptic spasms; atypical childhood epilepsy with centrotemporal spikes; photosensitive occipital lobe epilepsy | 99.77% each | L4 | Indirect and weak literature only. | | 2, 8, 9, 10 | Perioral myoclonia with absences; GRIN2A-related epileptic encephalopathy; restless legs syndrome; polymicrogyria with optic nerve hypoplasia | 99.07–99.79% | L5 | Prediction score only, with no trials or literature. Hold. |
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.