Ipratropium
| Evidence Level: L5 | Predicted Indications: 9 |
Table of Contents
Ipratropium: Nasal cavity disease
One-Sentence Summary
Ipratropium is an inhaled anticholinergic bronchodilator, originally used for chronic obstructive pulmonary disease (COPD), bronchitis, emphysema and rhinitis. The TxGNN model predicts it may be effective for nasal cavity disease, with 25 clinical trials and 20 publications retrieved for this prediction. This prediction largely confirms existing on-label use rather than representing a true new indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Nasal cavity disease |
| TxGNN Prediction Score | 0.9986 |
| Evidence Level | L5 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| 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. From the literature, ipratropium bromide is a non-selective muscarinic antagonist. It blocks acetylcholine-mediated (vagal) bronchoconstriction in airway smooth muscle, which produces bronchodilation.
The other predicted indications (ranks 2 to 10) are far weaker. Nasal cavity disease is consistent with the approved rhinitis use but has no trials. Pharyngitis, tracheal disease and anaphylaxis have only indirect or preclinical evidence. Acute laryngopharyngitis, papillary conjunctivitis, Rienhoff syndrome and food-dependent exercise-induced anaphylaxis are model predictions only. Respiratory malformation rests on a very small, loosely matched study.
Clinical Trial Evidence
The 10 most relevant trials are listed below. No ANZCTR identifiers were available in the data compiled for this report.
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT02177253 | Phase 3 | Completed | 1118 | 12-week double-blind comparison of ipratropium/salbutamol via Respimat with COMBIVENT aerosol, ipratropium alone and placebo in COPD |
| NCT02172469 | Phase 3 | Completed | 215 | Tiotropium 18 µg once daily vs Atrovent MDI in COPD (bronchodilator efficacy and safety) |
| NCT00239434 | Phase 3 | Completed | 200 | Tiotropium once daily vs Atrovent MDI four times daily in COPD |
| NCT01136421 | Phase 3 | Completed | 124 | Magnesium sulfate vs ipratropium, each added to short-acting β2 agonist, in acute exacerbation of COPD |
| NCT01415518 | Phase 4 | Completed | 581 | Symbicort added to Atrovent plus theophylline in severe COPD |
| NCT00371527 | N/A | Completed | 200 | Randomised, double-blind, placebo-controlled trial of ipratropium for acute bronchitis without underlying lung disease |
| NCT02172404 | Phase 3 | Completed | 160 | HandiHaler vs MDI administration technique in COPD (device-focused, not efficacy) |
| NCT02686086 | N/A | Completed | 60 | Vibrating mesh vs jet nebuliser bronchodilator delivery in COPD (pilot) |
| NCT01691482 | Phase 4 | Completed | 56 | 4-week crossover study of daily lung function with albuterol and ipratropium, alone and combined, in COPD |
| NCT06918418 | Phase 4 | Completed | 60 | Salbutamol alone vs salbutamol plus ipratropium in children with acute asthma |
Several other registered trials were withdrawn (0 enrolled) or terminated with very few participants (for example NCT04446637, NCT02235428 and NCT02458482) and provide no usable evidence.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 26391969 | 2015 | Systematic review (Cochrane) | Cochrane Database Syst Rev | Tiotropium vs ipratropium bromide in stable COPD |
| 24043433 | 2013 | Systematic review (Cochrane) | Cochrane Database Syst Rev | Earlier version of the tiotropium vs ipratropium comparison in COPD |
| 35616126 | 2022 | Systematic review (Cochrane) | Cochrane Database Syst Rev | Magnesium sulfate as adjunct treatment in COPD exacerbations (ipratropium is a comparator context) |
| 20163324 | 2010 | Review | Expert Opin Drug Metab Toxicol | Mechanism, efficacy and safety of albuterol, ipratropium and their combination in COPD |
| 23170031 | 2012 | Review | Ann Pharmacother | Efficacy and safety of ipratropium combined with tiotropium in COPD |
| 2977109 | 1988 | Review | Clin Pharm | Chemistry, pharmacology, efficacy, adverse effects and dosage of ipratropium in obstructive lung disease |
| 10565879 | 1999 | Review | Respir Care Clin N Am | Antimuscarinic bronchodilators in COPD; ipratropium effective alone and with albuterol |
| 15987237 | 2005 | Review | Treat Respir Med | Ipratropium HFA formulation approved in the US for maintenance treatment of bronchospasm |
| 38457591 | 2024 | Retrospective study | Medicine | Probiotics added to budesonide and ipratropium in COPD (118 patients), assessing lung function and gut microbiota |
| 25515181 | 2015 | Guideline | Basic Clin Pharmacol Toxicol | Finnish guideline on diagnosis and pharmacotherapy of stable COPD |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 1542E | Atrovent | Nebuliser solution, ipratropium bromide 250 micrograms (as monohydrate) in 1 mL single dose units, 30 | Not stated in the data compiled for this report |
Safety Considerations
The data compiled for this report do not include label warnings or contraindications. Please refer to the TGA-approved Product Information (PI) for these.
- Disease contraindications flagged in the knowledge graph (not taken from label text, so they should be verified against the PI): angle-closure glaucoma, benign prostatic hyperplasia and bladder neck obstruction, long QT syndrome, hypertension, coronary artery disease and myocardial ischaemia, hyperthyroidism, diabetes mellitus and diabetic ketoacidosis, metabolic acidosis, epilepsy, potassium deficiency and sudden cardiac arrest.
- Drug interactions: 100 interactions were found. All 19 listed in the compiled data are rated Moderate and mostly involve additive anticholinergic effects. Examples are atropine, hyoscyamine, glycopyrronium, scopolamine, trospium, promethazine and chlorpheniramine. Others include inhaled insulin, prucalopride, eluxadoline and aclidinium.
- Case reports in the literature: unilateral mydriasis after inhalation in an infant, and one case of severe anaphylaxis after inhaled ipratropium.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple completed Phase 3 trials (including one with 1118 participants) and reviews support ipratropium in obstructive airway disease. The indication text for the Australian ARTG entry and the safety data are also missing. The predicted indications are rated L3 to L5 and should be held or treated as a research question.
To proceed, the following is needed:
- The TGA-approved Product Information (PI), to confirm the approved indications, warnings and contraindications (a blocking data gap)
- Mechanism of action data from DrugBank
- A check of whether obstructive lung disease is already covered by the existing ARTG indication, which would make a new submission unnecessary
- A review of the knowledge graph contraindications (glaucoma, urinary retention, cardiac conditions) against the PI, along with a plan for monitoring anticholinergic interactions
- For rhinitis-related predictions (nasal cavity disease), direct clinical evidence, as no trials were found
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.