Carbon Monoxide

Evidence Level: L5

Predicted Indications: 10

Carbon Monoxide

Pharmacist Assessment Report

Carbon Monoxide: From Pulmonary Diffusion Testing Gas to Sclerosing Cholangitis

One-Sentence Summary

Carbon monoxide is marketed in Canada only as components of gas mixtures. The product names point to lung diffusion testing, but no approved indication text is on file. The TxGNN model predicts it may be effective for sclerosing cholangitis. There are currently 0 clinical trials and 0 publications supporting this specific prediction, so it rests on the model score alone.

Quick Overview

Item	Content
Original Indication	Not stated in the licence data (product names suggest lung diffusion test gas mixtures)
Predicted New Indication	Sclerosing cholangitis
TxGNN Prediction Score	0.9975
Evidence Level	L5
Canada Market Status	Marketed (marketed DINs: 4 of 4)
Number of DINs	4 (marketed: 4)
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism-of-action data is not available for carbon monoxide. Endogenous carbon monoxide is produced when heme oxygenase breaks down heme. At low concentrations it has anti-inflammatory and cytoprotective effects. This is the only plausible link to a chronic inflammatory bile duct disease such as sclerosing cholangitis.

This link is speculative. The data compiled for this report contain no clinical or literature evidence connecting carbon monoxide to sclerosing cholangitis. The relationship between the drug’s current use (a diagnostic gas for lung function testing) and the predicted liver and bile duct indication has not been assessed. Whether an inhaled gas can reach the target tissue at a safe dose is also unassessed. The high score should be treated as a hypothesis, not as support for efficacy.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

Currently no related literature available.

Canada Market Information

DIN	Product Name	Dosage Form	Approved Indication
02154773	CO-HE-O2-N2 Mixture	Not stated	Not stated
02014424	Carbon Monox, Helium, Oxygen, Nitrogen L.D.M.	Not stated	Not stated
02182238	CO-NE-O2-N2 Mixture	Not stated	Not stated
00588075	Lung Diffusion Test Mix NO NE CO	Not stated	Not stated

All four authorizations are valid licences.

Safety Considerations

Please refer to the package insert for safety information.

Carbon monoxide is a recognised toxic gas. It binds hemoglobin and causes tissue hypoxia. Any therapeutic use would require strict control of carboxyhemoglobin levels.

Conclusion and Next Steps

Decision: Hold

Rationale: The prediction has no supporting trials or publications, so the evidence level is L5. The link to sclerosing cholangitis is mechanistically speculative. No indication text or safety label data is available for the Canadian products.

To proceed, the following is needed:

Health Canada package insert warnings and contraindications (a blocking gap for safety screening)
Detailed mechanism of action data
A targeted literature search on the heme oxygenase/carbon monoxide pathway in cholestatic and bile duct disease
An assessment of route compatibility and a safe dosing strategy for the target tissue

Note on other predictions: Among the top 10 predictions, pulmonary hypertension (rank 8, L3) has the most relevant evidence. This includes preclinical work showing carbon monoxide reversing established pulmonary hypertension, a phase 1 trial of inhaled carbon monoxide in neonatal pulmonary hypertension (NCT01818843, n=24, status unknown), and a withdrawn phase 1/2 trial in severe pulmonary arterial hypertension (NCT01523548, n=0). It may be a better candidate for follow-up as a research question. Several cardiac-rhythm predictions are contradicted by evidence that carbon monoxide is arrhythmogenic.

Disclaimer

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