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 and intranasal anticholinergic (muscarinic antagonist) originally used for chronic obstructive pulmonary disease (COPD), rhinitis, bronchitis and emphysema. The TxGNN model predicts it may be effective for obstructive lung disease, with 25 clinical trials and 20 publications retrieved. This prediction largely confirms an existing use rather than a true new indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic obstructive pulmonary disease (COPD), allergic rhinitis, vasomotor rhinitis, bronchitis, emphysema (from the knowledge graph; no approved indication text is available from New Zealand licences) |
| Predicted New Indication | Obstructive lung disease |
| TxGNN Prediction Score | 99.97% |
| Evidence Level | L1 |
| New Zealand Market Status | Cancelled only (no currently valid licences) |
| Number of Authorizations | 5 (all cancelled) |
| 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. Pharmacology records show that ipratropium binds muscarinic receptors M1 to M5 (CHRM1–CHRM5). It is a non-selective muscarinic antagonist, and its recorded clinical use is bronchospasm associated with COPD.
Blocking M3 receptors on airway smooth muscle reduces vagally mediated bronchoconstriction, which is the core physiological problem in obstructive lung disease. The predicted indication overlaps heavily with the drug's original uses (COPD, bronchitis, emphysema), so this is mostly confirmation of an established use rather than true repurposing.
Lower-ranked predictions (nasal cavity disease, pharyngitis, tracheal disease, anaphylaxis and others) have much weaker support. Most have only indirect or preclinical evidence, or none at all, and are not recommended for advancement.
Clinical Trial Evidence
The 10 most relevant trials for obstructive lung disease are shown below (25 were retrieved).
| 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 |
| NCT01415518 | Phase 4 | Completed | 581 | Symbicort added to Atrovent plus theophylline in severe COPD |
| NCT01136421 | Phase 3 | Completed | 124 | Magnesium sulfate vs ipratropium bromide added to short-acting β2 agonist in COPD exacerbations |
| NCT02172469 | Phase 3 | Completed | 215 | Tiotropium vs Atrovent MDI in COPD |
| NCT00239434 | Phase 3 | Completed | 200 | Tiotropium once daily vs Atrovent MDI four times daily in COPD |
| NCT02172404 | Phase 3 | Completed | 160 | HandiHaler vs pressurised MDI: administration technique and ease of use in COPD (delivery, not efficacy) |
| NCT02260011 | Phase 2 | Completed | 41 | Ipratropium HFA-134a vs Atrovent CFC aerosol: bronchodilator comparability in COPD |
| NCT01691482 | Phase 4 | Completed | 56 | Daily lung function with albuterol and ipratropium, alone and combined, in COPD |
| NCT00371527 | NA | Completed | 200 | Randomised placebo-controlled trial of ipratropium for acute bronchitis in people without underlying lung disease |
| NCT04446637 | Phase 3 | Withdrawn | 0 | Ipratropium/levosalbutamol fixed-dose combination vs free combination in COPD; no participants enrolled |
Only one large, completed, directly relevant Phase 3 trial (NCT02177253) was graded as strong direct efficacy evidence. Several trials test combinations or compare devices, so they do not isolate the effect of ipratropium alone.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 26391969 | 2015 | Cochrane review | Cochrane Database Syst Rev | Tiotropium vs ipratropium bromide in stable COPD; both are recognised treatments |
| 24043433 | 2013 | Cochrane review | Cochrane Database Syst Rev | Earlier version of the tiotropium vs ipratropium comparison |
| 35616126 | 2022 | Review | Cochrane Database Syst Rev | Magnesium sulfate as an adjunct in COPD exacerbations |
| 23170031 | 2012 | Review | Ann Pharmacother | Efficacy and safety of ipratropium used together with tiotropium in COPD |
| 20163324 | 2010 | Review | Expert Opin Drug Metab Toxicol | Mechanism, efficacy and safety of albuterol, ipratropium and their combination in COPD |
| 10565879 | 1999 | Review | Respir Care Clin N Am | Ipratropium is a safe and effective bronchodilator in COPD, alone and with albuterol |
| 2977109 | 1988 | Review | Clin Pharm | Pharmacology, kinetics, efficacy, adverse effects and dosing of ipratropium in obstructive lung disease |
| 25515181 | 2015 | Guideline | Basic Clin Pharmacol Toxicol | Finnish guideline for diagnosis and pharmacotherapy of stable COPD |
| 38457591 | 2024 | Retrospective study | Medicine | Probiotics added to budesonide plus ipratropium in 118 COPD patients |
| 15987237 | 2005 | Review | Treat Respir Med | Ipratropium HFA metered-dose inhaler for maintenance treatment of bronchospasm |
The literature is dominated by reviews. No randomised trial publications were identified among the retrieved items.
New Zealand Market Information
All five licences are cancelled, and no approved indication text is available.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 2643154 | Accord | Nebuliser solution, 250 mcg/ml, 2 ml ampoule | Not available (cancelled) |
| 2145782 | Atrovent | Aerosol inhaler, 20 mcg per dose, CFC-free | Not available (cancelled) |
| 2154307 | Univent | Nebuliser solution, 250 mcg/ml, 2 ml ampoule | Not available (cancelled) |
| 2372908 | Univent | Aqueous nasal spray, 0.03% | Not available (cancelled) |
| 2724863 | Ipratropium Viatris | Nebuliser solution, 250 mcg/ml, 2 ml ampoule | Not available (cancelled) |
Safety Considerations
- Disease associations flagged as contraindications in the knowledge graph (not taken from label text): hypertension, long QT syndrome, epilepsy, potassium deficiency, diabetes mellitus and diabetic ketoacidosis, benign prostatic hyperplasia, bladder neck obstruction, ocular hypertension, angle-closure glaucoma, acidosis, sudden cardiac arrest, heart conduction disease, hyperthyroidism/Graves disease/thyrotoxicosis, myocardial ischemia and coronary artery disease. These need verification against the current package insert.
- Drug interactions: The interaction query returned only receptor-binding records (muscarinic M1–M5), with no drug–drug interaction entries.
- Other signals from the literature: A case report describes severe anaphylaxis after ipratropium inhalation, and another describes unilateral mydriasis after inhalation in an infant.
Package insert warnings and contraindications could not be retrieved, so please refer to the package insert for authoritative safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale:
- Obstructive lung disease is essentially an established use of ipratropium. A large completed Phase 3 trial and extensive review literature support it, but the indication is not new.
- There are no valid New Zealand licences at present, and package insert safety data are missing, so any reintroduction needs regulatory and safety work first.
- The other predicted indications are not recommended to advance. Nasal cavity disease and respiratory malformation are research questions at most. Pharyngitis, acute laryngopharyngitis, papillary conjunctivitis, Rienhoff syndrome, tracheal disease, anaphylaxis and food-dependent exercise-induced anaphylaxis are on Hold.
To proceed, the following is needed:
- Medsafe package insert warnings and contraindications, which block safety screening
- Detailed mechanism of action data from DrugBank
- Clarification of why all New Zealand licences were cancelled, and whether a new application or a different product is required
- A review of the knowledge-graph contraindications (cardiovascular, glaucoma, urinary retention and others) against label text
- Confirmation of which formulation (nebulised, inhaler or nasal) is intended for any new use
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.