Methoxyflurane
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Methoxyflurane: From Inhaled Acute Pain Relief to Insomnia
One-Sentence Summary
Methoxyflurane is a volatile inhaled agent, marketed in Singapore as Penthrox, and published studies describe it mainly as a short-acting analgesic and sedative for procedural and acute pain. The TxGNN model predicts it may be effective for insomnia, but no clinical trials and no publications were found for this indication, so the prediction rests on the model score alone. Among the other predictions, anxiety has the most supporting literature (17 publications, none of them registered trials).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the Singapore registration data. Published literature describes use as an inhaled analgesic for acute and procedural pain. |
| Predicted New Indication | Insomnia |
| TxGNN Prediction Score | 98.01% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data are not available in the data compiled for this report. Methoxyflurane is a volatile central nervous system (CNS) depressant with anaesthetic and analgesic properties. A sedative effect is therefore plausible, which could loosely connect it to sleep.
The link is weak, however. Methoxyflurane is an acute, short-acting inhaled agent used for brief procedures. Insomnia is usually a chronic condition needing repeated, convenient dosing, and nothing in the data supports chronic or repeated use of an inhaled anaesthetic for sleep. The high score most likely reflects similarity to other sedating drugs in the model's knowledge graph, not direct evidence.
For context, the other predicted indications are mostly migraine variants, mood and anxiety disorders, and two rare skin conditions. The skin conditions have no plausible mechanistic link and are likely artefacts of the graph. The only prediction with meaningful supporting literature is anxiety. There, mouse studies show diazepam-like effects of methoxyflurane, and several procedural studies report anxiety relief alongside pain relief. That benefit appears to be secondary to analgesia and sedation, not a primary indication.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available for insomnia.
For reference, the strongest evidence among the other predictions concerns anxiety in procedural settings. This is indirect evidence, and anxiety was not clearly the primary endpoint in these studies.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 38923825 | 2024 | RCT | Journal of Medical Imaging and Radiation Oncology | MONITOR trial: methoxyflurane for procedural sedation and pain in interventional radiology |
| 40769179 | 2025 | RCT | Canadian Urological Association Journal | Methoxyflurane added to local anaesthesia for pain and anxiety in scrotal surgery |
| 24644183 | 2014 | RCT | BMJ Supportive & Palliative Care | Randomised, double-blind, placebo-controlled study of procedural pain in bone marrow biopsy |
| 23810328 | 2013 | RCT | Gastrointestinal Endoscopy | Patient-controlled methoxyflurane vs. endoscopist-provided sedation for colonoscopy |
| 22925206 | 2014 | Case series | International Wound Journal | Pain and anxiety relief during burn wound care |
| 40170612 | 2025 | Review | Current Opinion in Supportive and Palliative Care | Applications of inhaled methoxyflurane in patients with cancer |
| 8894586 | 1996 | Preclinical | European Journal of Pharmacology | Inhalants including methoxyflurane showed anxiety-modulating effects in a mouse elevated plus-maze |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14854P | PENTHROX INHALATION LIQUID 99.9% (Medical Developments International Limited) | Inhalant | Not listed in the registration data |
Safety Considerations
- Drug Interactions: The interaction screening found 51 interacting drugs. The 20 listed in the data compiled for this report are:
- Major: doxycycline, tetracycline, minocycline, epinephrine, and iothalamic acid.
- Moderate:
- Amphotericin B (including the lipid complex, cholesteryl sulfate and liposomal forms).
- Aminosalicylates: mesalazine, balsalazide, olsalazine and sulfasalazine.
- Opioids: morphine and opium.
- Antibiotics: vancomycin, neomycin and streptomycin.
- Others: exenatide and ethanol.
- Renal toxicity: Nephrotoxicity at high doses is a known concern with methoxyflurane. It matters most for repeated exposure, which a chronic condition such as insomnia would involve.
Please refer to the package insert for the full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The insomnia prediction has no clinical trials or publications behind it (Evidence Level L5). Methoxyflurane is an acute inhaled agent, and repeated or chronic exposure raises renal safety concerns. The mechanistic link is plausible only in a general sense.
To proceed, the following is needed:
- Mechanism-of-action data for methoxyflurane
- The package insert warnings and contraindications from the Singapore regulator (HSA). Their absence currently blocks any safety screening.
- Preclinical or early clinical studies of sedation or sleep outcomes, with a clear rationale for a route and dosing schedule suited to sleep
- If the team wants to pursue a better-supported direction, a separate review of anxiety (procedural anxiety). This would need studies that treat anxiety as a primary endpoint and a repeated-exposure safety assessment.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.