Clobazam

證據等級: L5

預測適應症: 10 個

taiwan_regulatory.licenses is empty (0 UK marketing authorisations), so the UK Market Information table is replaced with a one-line statement per the “omit empty sections” rule.
original_indications and original_moa are both empty/[Data Gap] in this pack. Per the fallback rule for missing MOA, I’ve stated Clobazam’s original indication using its well-established pharmacological classification (benzodiazepine anticonvulsant/anxiolytic) rather than fabricating specific trial data.
Clobazam is not an antineoplastic agent, so the Cytotoxicity section is omitted entirely.
The evidence pack’s recommendation field for rank-1 (“Research Question”) doesn’t map directly to the required Go/Hold/Proceed with Guardrails scale — given L4 evidence (case series only, no RCTs), a Blocking safety data gap (DG001), and zero UK marketing authorisations, I mapped this to Hold.

One-Sentence Summary

Clobazam is a 1,5-benzodiazepine anticonvulsant, established as adjunctive therapy for epilepsy (including Lennox-Gastaut syndrome) and for anxiety disorders. The TxGNN model predicts it may be effective for febrile infection-related epilepsy syndrome (FIRES), but this direction is currently supported by only 0 clinical trials and 2 publications (both case series involving related GABA-ergic agents, not clobazam itself).

Quick Overview

Item	Content
Original Indication	Epilepsy (adjunctive anticonvulsant therapy, e.g. Lennox-Gastaut syndrome); anxiety disorders (based on established drug classification — no licence data available in this evidence pack)
Predicted New Indication	Febrile infection-related epilepsy syndrome (FIRES)
TxGNN Prediction Score	99.82%
Evidence Level	L4
UK Market Status	Not Marketed
Number of Marketing Authorisations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in this evidence pack. Based on known pharmacological information, clobazam is a 1,5-benzodiazepine that acts as a positive allosteric modulator of the GABA-A receptor, enhancing inhibitory neurotransmission and suppressing abnormal cortical excitability. Its efficacy as an adjunctive anticonvulsant in focal and generalised epilepsies, including refractory syndromes, is well established.

FIRES is a severe, treatment-resistant form of new-onset refractory status epilepticus that typically requires prolonged pharmacological coma with GABA-ergic anaesthetics (e.g. midazolam) to control seizures. Because clobazam shares the same GABA-A receptor mechanism as the agents used acutely in FIRES, there is a plausible pharmacological rationale for its use as a maintenance or step-down anticonvulsant once patients are being weaned from anaesthetic coma.

However, the available literature does not evaluate clobazam directly in FIRES — the two retrieved publications discuss enteral lorazepam and perampanel, not clobazam, as weaning or adjunctive strategies. The mechanistic link is therefore indirect (drug-class analogy) rather than drug-specific evidence, which is why this prediction remains at evidence level L4.

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 (a related GABA-ergic benzodiazepine) was an effective weaning strategy in midazolam-dependent FIRES patients, supporting the broader rationale for benzodiazepine step-down therapy in this condition.
39958143	2025	Case report	Cureus	Perampanel reduced barbiturate dependency in a paediatric FIRES case, illustrating that non-anaesthetic adjunctive anticonvulsants can play a role in weaning protocols, though this does not directly involve clobazam.

UK Market Information

Clobazam currently holds no UK marketing authorisation on record in this evidence pack (0 licences; market status: Not Marketed). Prescribers should verify current MHRA/electronic Medicines Compendium (eMC) status directly, as products (e.g. Frisium) may be available via named-patient or specialist import routes even where standard marketing authorisation data is not captured here.

Safety Considerations

Please refer to the SmPC and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.

(Note: this evidence pack flags a Blocking data gap — MHRA warnings/contraindications data was not available — which by itself is sufficient to prevent a preliminary safety assessment (S1) for this candidate.)

Conclusion and Next Steps

Decision: Hold

Rationale: Evidence is currently limited to mechanistic rationale and drug-class analogy (L4) — no clinical trials and no publications directly evaluating clobazam in FIRES exist. Combined with the absence of a UK marketing authorisation and a Blocking-severity gap in MHRA safety data (warnings/contraindications), this candidate is not ready to proceed past the research-question stage.

To proceed, the following is needed:

MHRA SmPC/PIL retrieval for clobazam warnings and contraindications (currently a Blocking data gap)
Confirmed mechanism of action data from DrugBank or equivalent source
Drug-specific clinical evidence (case series, cohort study, or trial) evaluating clobazam — not just related benzodiazepines — in FIRES
Regulatory pathway assessment given current “Not Marketed” status in the UK
Consider prioritising higher-evidence candidates identified in the same evidence pack — notably benign occipital epilepsy (evidence level L2, supported by multiple Cochrane systematic reviews and direct clobazam literature, recommendation: Proceed with Guardrails), which may represent a more actionable near-term repurposing direction for this drug.
Disclaimer

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