Ipratropium
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
Ipratropium: From Chronic Obstructive Pulmonary Disease to Obstructive Lung Disease
One-Sentence Summary
Ipratropium is an inhaled anticholinergic bronchodilator, originally used for chronic obstructive pulmonary disease (COPD), allergic and vasomotor rhinitis, and bronchitis. The TxGNN model predicts it may be effective for obstructive lung disease, which overlaps heavily with its existing COPD and bronchial disease uses. The data compiled for this report include 25 clinical trials and 20 publications for this indication, including one large completed Phase 3 trial (n=1,118).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic obstructive pulmonary disease, allergic rhinitis, vasomotor rhinitis, bronchitis, common cold, pulmonary emphysema (from the TxGNN knowledge graph; Singapore label text was not available) |
| Predicted New Indication | Obstructive lung disease |
| TxGNN Prediction Score | 99.97% |
| Evidence Level | L1 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 6 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, ipratropium is a muscarinic antagonist. It blocks M3 receptor-mediated bronchoconstriction in airway smooth muscle by interrupting vagally mediated cholinergic signalling.
This matches the pathophysiology of obstructive lung disease directly. The predicted indication overlaps with the already-established COPD and bronchial disease uses. It is therefore closer to an on-label or near-label use than to true repurposing. The high TxGNN score reflects this overlap.
Other predicted indications in the data are much weaker. Nasal cavity disease is plausible and partly on-label through the rhinitis uses. Pharyngitis, tracheal disease and anaphylaxis have only indirect or preclinical support. Several others (acute laryngopharyngitis, papillary conjunctivitis, Rienhoff syndrome, food-dependent exercise-induced anaphylaxis) have no supporting studies at all. This report focuses on the top-ranked indication.
Clinical Trial Evidence
The table lists the 10 most relevant of the 25 trials, prioritising direct ipratropium evidence in obstructive airway disease.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02177253 | Phase 3 | Completed | 1118 | 12-week comparison of ipratropium/salbutamol via Respimat vs COMBIVENT aerosol, ipratropium Respimat and placebo in COPD |
| NCT02172469 | Phase 3 | Completed | 215 | Tiotropium vs Atrovent (ipratropium) MDI in COPD |
| NCT00239434 | Phase 3 | Completed | 200 | Once-daily tiotropium vs ipratropium MDI four times daily in COPD |
| NCT01136421 | Phase 3 | Completed | 124 | Magnesium sulfate vs ipratropium bromide added to short-acting beta-agonist in COPD exacerbation |
| NCT02172404 | Phase 3 | Completed | 160 | HandiHaler vs pMDI administration technique and ease of use in COPD (indirect) |
| NCT01415518 | Phase 4 | Completed | 581 | Symbicort added to Atrovent plus theophylline vs Atrovent plus theophylline in severe COPD |
| NCT01691482 | Phase 4 | Completed | 56 | 4-week crossover of daily bronchodilator response to albuterol and ipratropium, alone and combined, in COPD |
| NCT00371527 | NA | Completed | 200 | Ipratropium vs placebo in acute bronchitis without underlying lung disease (tangential population) |
| NCT02686086 | NA | Completed | 60 | Lung volume and symptom scores after bronchodilator via vibrating mesh vs jet nebuliser in COPD |
| NCT02235428 | Phase 4 | Terminated | 3 | Ipratropium added to high-dose salbutamol in children's acute asthma; too small to inform efficacy |
Some of these trials are indirect: they use ipratropium as a comparator or background therapy, or they test device technique rather than efficacy. Two trials were withdrawn with no participants (NCT04446637, NCT02458482).
Literature Evidence
The table lists 10 of the 20 publications (reviews and systematic reviews first).
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 26391969 | 2015 | Systematic review | Cochrane Database Syst Rev | Tiotropium vs ipratropium bromide in stable COPD |
| 24043433 | 2013 | Systematic review | Cochrane Database Syst Rev | Earlier version of the tiotropium vs ipratropium comparison |
| 35616126 | 2022 | Systematic review | Cochrane Database Syst Rev | Magnesium sulfate for COPD exacerbations (indirect) |
| 23170031 | 2012 | Review | Ann Pharmacother | Efficacy and safety of ipratropium combined with tiotropium in COPD |
| 20163324 | 2010 | Review | Expert Opin Drug Metab Toxicol | Albuterol, ipratropium and their combination in COPD: mechanism, efficacy and safety |
| 15257628 | 2004 | Review | Drugs | Ipratropium/fenoterol (Berodual) via Respimat in asthma and COPD |
| 15987237 | 2005 | Review | Treat Respir Med | Ipratropium HFA metered-dose inhaler for bronchospasm in COPD |
| 10565879 | 1999 | Review | Respir Care Clin N Am | Anticholinergic bronchodilators; spirometric bronchodilation with ipratropium alone and with albuterol |
| 2977109 | 1988 | Review | Clin Pharm | Pharmacology, efficacy, adverse effects and dosing of ipratropium in obstructive lung disease |
| 38457591 | 2024 | Retrospective study | Medicine | Probiotics plus budesonide and ipratropium in COPD (n=118) |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN10039P | STERI-NEB IPRATROPIUM NEBULISER SOLUTION 250 mcg/ml | Solution | Not listed in the data compiled |
| SIN02815P | ATROVENT SOLUTION 0.025% | Solution | Not listed in the data compiled |
| SIN07913P | DUOVENT UDVS NEBULISER SOLUTION | Solution | Not listed in the data compiled |
| SIN02664P | BERODUAL SOLUTION | Solution | Not listed in the data compiled |
| SIN11739P | BERODUAL N METERED DOSE INHALER | Aerosol, spray | Not listed in the data compiled |
A sixth licence, SIN09558P (COMBIVENT UNIT DOSE VIAL FOR INHALATION, solution), is also valid. All six registrations are valid, and none are cancelled.
Safety Considerations
Package-insert warnings and contraindications were not available for this report. Please refer to the package insert for authoritative safety information.
- Disease-level cautions (knowledge graph, not label text): Contraindication links were recorded for angle-closure glaucoma, ocular hypertension, benign prostatic hyperplasia, bladder neck obstruction, long QT syndrome, heart conduction disease, sudden cardiac arrest, hypertension, myocardial ischemia and coronary artery disease, hyperthyroidism, diabetes and diabetic ketoacidosis, epilepsy, and metabolic acidosis and potassium deficiency. Many of these may reflect combination products containing a beta-agonist (as in Berodual, Combivent and Duovent) rather than ipratropium alone. They should be verified against the label.
- Drug interactions: 100 interactions were found, all at the moderate level among those shown. The main ones are other anticholinergics and antimuscarinics (atropine, hyoscyamine, scopolamine, glycopyrronium, aclidinium, trospium, propantheline, dicyclomine), plus promethazine, chlorpheniramine, eluxadoline, prucalopride and inhaled insulin. The concern is additive anticholinergic effects.
- Reported adverse events in the literature: Unilateral mydriasis after inhalation (infant case report) and severe anaphylaxis after inhalation (case report).
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Ipratropium's anticholinergic bronchodilator mechanism fits obstructive lung disease, and the indication overlaps with its established COPD use. A large completed Phase 3 trial (n=1,118), several other Phase 3 trials, and Cochrane and narrative reviews support this. Many of the trials are indirect, so the evidence is strong for COPD but less certain for the broader label of obstructive lung disease. The safety label data are also missing.
To proceed, the following is needed:
- Singapore package insert (HSA) warnings, contraindications and approved indication text
- Mechanism of action data (DrugBank)
- Confirmation of the exact obstructive lung disease population (COPD vs asthma, including paediatric use) against the registered indications
- Attention to ocular, urinary and cardiac cautions and to anticholinergic interactions
Other predicted indications should stay on Hold, or be treated as research questions: nasal cavity disease and respiratory malformation have limited or indirect evidence, and the others have little or no supporting evidence. Anaphylaxis carries a safety signal.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.