Acetylcysteine
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
- Acetylcysteine
- Pharmacist Assessment Report
- Acetylcysteine: From Bronchitis and Paracetamol Poisoning to Thrombotic Disease
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Canada Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Acetylcysteine: From Bronchitis and Paracetamol Poisoning to Thrombotic Disease
One-Sentence Summary
Acetylcysteine is a mucolytic and antidote, originally used for bronchitis, paracetamol (acetaminophen) poisoning, cystic fibrosis and bronchiectasis. The TxGNN model predicts it may be effective for thrombotic disease, with 7 clinical trials and 20 publications currently supporting this direction. The strongest support is in thrombotic microangiopathy (transplant-associated TMA and TTP), and less so for general arterial or venous thrombosis.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Bronchitis, paracetamol poisoning, cystic fibrosis, bronchiectasis (approved indication text is not available for the Canadian licences) |
| Predicted New Indication | Thrombotic disease |
| TxGNN Prediction Score | 0.9996 |
| Evidence Level | L1 (see note below) |
| Canada Market Status | Marketed (marketed DINs: 3 of 3) |
| Number of DINs | 3 (marketed: 3) |
| Recommended Decision | Proceed with Guardrails |
Note on evidence level: one completed Phase 3 trial (NCT03252925) and one Phase 2/3 trial (NCT07279610, not yet completed) exist, so the L1 criterion of at least two completed Phase 3 RCTs is not strictly met. Because the results of the completed trial have not been verified, a conservative reading would be L2.
Why is This Prediction Reasonable?
Acetylcysteine is a thiol compound. It reduces disulfide bonds, which is the basis of its mucolytic action in the airway. Detailed mechanism-of-action data are not available in the compiled drug record, but the following mechanistic reasoning is supported by the literature compiled for this report.
In thrombotic thrombocytopenic purpura (TTP), ultra-large von Willebrand factor (VWF) multimers form platelet-rich clots in small vessels. By reducing disulfide bonds in these multimers, acetylcysteine may lower their platelet-binding and prothrombotic activity. It is also an antioxidant that may limit endothelial oxidative stress. This is supported by preclinical mouse and baboon TTP models (PMID 28011677).
The link to the original indications is the shared thiol chemistry: disulfide-bond reduction acts on mucins in the airway and on VWF multimers in the blood. The evidence is strongest for thrombotic microangiopathy and TTP-like conditions, and indirect for general arterial or venous thrombosis.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03252925 | Phase 3 | Completed | 170 | Safety and efficacy of N-acetylcysteine in transplant-associated thrombotic microangiopathy (TA-TMA); results should be checked before relying on them |
| NCT07279610 | Phase 2/3 | Active, not recruiting | 44 | Single-arm multicentre study of NAC in TA-TMA; follow-up to the earlier Phase 3 trial |
| NCT03636932 | Phase 2 | Completed | 40 | RENACTIF: randomized, double-blind, placebo-controlled cross-over trial of NAC on the thrombotic phenotype in renal insufficiency |
| NCT01808521 | Early Phase 1 | Completed | 3 | Pilot of intravenous NAC in suspected TTP; too small to support efficacy |
| NCT04368598 | Phase 2 | Unknown | 44 | High-dose dexamethasone plus acetylcysteine in newly diagnosed immune thrombocytopenia (indirect relevance) |
| NCT05551624 | Early Phase 1 | Completed | 15 | Atorvastatin plus NAC on platelet count in steroid-resistant or relapsed ITP (indirect relevance) |
| NCT03460808 | Phase 1/2 | Unknown | 200 | Atorvastatin, acetylcysteine and danazol in steroid-resistant or relapsed ITP (indirect relevance) |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 41977015 | 2026 | Systematic review | J Clin Med | Systematic review and critical appraisal of NAC therapy in TTP |
| 42338865 | 2026 | Systematic review | Cureus | Systematic review of NAC as adjunctive therapy in TTP |
| 37311880 | 2023 | Cohort study | Ann Hematol | Association of NAC treatment with in-hospital mortality in acquired TTP; use of NAC remains controversial |
| 28011677 | 2017 | Preclinical | Blood | NAC in mouse and baboon models of TTP |
| 32243196 | 2020 | Review | Expert Rev Hematol | Repurposed drugs and novel agents in TTP, including NAC |
| 28416507 | 2017 | Review | Blood | Overview of TTP pathophysiology and treatment |
| 33540569 | 2021 | Review | J Clin Med | TTP pathophysiology, diagnosis and management |
| 36410267 | 2022 | Review | J Infect Public Health | NAC in COVID-19, which involves oxidative stress and a prothrombotic state |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02243098 | Acetylcysteine Solution | Not specified | Not specified |
| 02459906 | Acetylcysteine Solution USP | Not specified | Not specified |
| 02538431 | Acetylcysteine Solution USP | Not specified | Not specified |
Safety Considerations
- Contraindications suggested by the drug-disease knowledge graph (not label text): peptic ulcer disease, hypotensive disorder, respiratory failure, asthma, bronchial disease, esophageal varices.
- Drug interactions: 100 interactions were found in total. The most notable are insulin human (inhalation, rapid acting), which is rated Moderate, and activated charcoal, which is rated Minor. Most others, including mannitol, bupropion, calcitriol, pantoprazole, glimepiride, doxycycline, morphine, metformin, omeprazole, sucralfate, rosiglitazone, lansoprazole, cimetidine, vancomycin, atropine, lactulose, triamcinolone and prednisone, have no severity rating.
For label warnings and contraindications, please refer to the package insert.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: A completed Phase 3 trial and a follow-up Phase 2/3 trial in transplant-associated thrombotic microangiopathy, plus systematic reviews and preclinical TTP data, give a plausible and directionally consistent signal. The evidence is much weaker for general thrombotic disease, and the TTP evidence is small and still debated.
To proceed, the following is needed:
- Review of the results of NCT03252925 and, when available, NCT07279610
- Definition of the target population, such as TA-TMA or TTP rather than thrombosis broadly
- Health Canada package insert warnings, contraindications and approved indications for the three licences
- Detailed mechanism-of-action data
- Review of the knowledge-graph contraindications (asthma, bronchial disease, respiratory failure, hypotension, peptic ulcer, esophageal varices) against the intended patient group, and of the interaction profile
Other predicted indications (closed-angle glaucoma, nasal cavity disease, dry eye syndrome, pharyngitis, acute laryngopharyngitis, tracheal disease, transient ischemic attack, laryngotracheitis, angle-closure glaucoma) are outside the scope of this report. Dry eye syndrome has some clinical evidence (topical chitosan-N-acetylcysteine trials and RCTs) and may merit a separate evaluation.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.