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) and rhinitis. The TxGNN model predicts it may be effective for obstructive lung disease, with 26 registered clinical trials and 20 publications currently supporting this direction. This prediction largely overlaps with an established use, so it is not a true repurposing finding.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic obstructive pulmonary disease (COPD) and related airway and nasal conditions (the UK authorisation record contains no indication text) |
| Predicted New Indication | Obstructive lung disease |
| TxGNN Prediction Score | 99.97% |
| Evidence Level | L1 |
| UK Market Status | Marketed |
| Number of Marketing Authorisations | 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. Ipratropium is a muscarinic (anticholinergic) antagonist. It blocks acetylcholine-mediated bronchoconstriction in airway smooth muscle. It is a quaternary ammonium derivative of atropine and is poorly absorbed after inhalation, so its action is mainly local.
COPD is itself an obstructive lung disease, so the predicted indication overlaps closely with the drug’s established use. The mechanism is the same: reducing vagal tone in the airways to relieve bronchoconstriction. Ipratropium is commonly combined with salbutamol, a beta-2 agonist. The two drugs act through different pathways and their effects are additive.
This prediction should therefore be seen as confirming existing use rather than opening a new therapeutic area.
Clinical Trial Evidence
The data include 26 registered trials. The most relevant are listed below.
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT02177253 | Phase 3 | Completed | 1118 | 12-week comparison of ipratropium/salbutamol via Respimat versus Combivent aerosol, ipratropium alone and placebo in COPD |
| NCT01136421 | Phase 3 | Completed | 124 | Magnesium sulfate versus ipratropium, each with a short-acting beta-agonist, in acute COPD exacerbation |
| NCT02172469 | Phase 3 | Completed | 215 | Tiotropium versus Atrovent (ipratropium) MDI in COPD |
| NCT00239434 | Phase 3 | Completed | 200 | Once-daily tiotropium versus Atrovent MDI four times daily in COPD |
| NCT02172404 | Phase 3 | Completed | 160 | Inhaler technique and ease of use, HandiHaler versus MDI, in COPD (device study, not efficacy) |
| NCT00371527 | N/A | Completed | 200 | Randomised, placebo-controlled trial of ipratropium in acute bronchitis without underlying lung disease |
| NCT01691482 | Phase 4 | Completed | 56 | Four-week crossover of salbutamol and ipratropium, alone and combined, in COPD |
| NCT06918418 | Phase 4 | Completed | 60 | Salbutamol alone versus salbutamol plus ipratropium in acute childhood asthma |
| NCT04446637 | Phase 3 | Withdrawn | 0 | Ipratropium/levosalbutamol fixed-dose combination in COPD; no participants enrolled |
| NCT02235428 | Phase 4 | Terminated | 3 | Ipratropium plus high-dose salbutamol in acute asthma in young children; too small to inform |
Only one trial, NCT02177253, is both large and directly relevant. Several others are small, terminated or withdrawn, or concern device use rather than efficacy.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 26391969 | 2015 | Cochrane review | Cochrane Database Syst Rev | Tiotropium versus ipratropium bromide in stable COPD |
| 24043433 | 2013 | Cochrane review | Cochrane Database Syst Rev | Earlier version of the same tiotropium versus ipratropium comparison |
| 35616126 | 2022 | Cochrane 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/salbutamol, ipratropium and their combination in COPD |
| 25515181 | 2015 | Guideline | Basic Clin Pharmacol Toxicol | Finnish guidelines for diagnosis and pharmacotherapy of stable COPD |
| 38457591 | 2024 | Retrospective study | Medicine | Probiotics added to budesonide and ipratropium in 118 COPD patients, assessing lung function and gut microbiota |
| 10565879 | 1999 | Review | Respir Care Clin N Am | Ipratropium is an effective bronchodilator in COPD, alone and with albuterol |
| 6129123 | 1982 | Review | Drugs | Anticholinergics, beta-agonists and methylxanthines are additive in combination |
| 2977109 | 1988 | Review | Clin Pharm | Pharmacology, efficacy, adverse effects and dosing of ipratropium in obstructive lung disease |
UK Market Information
| Marketing Authorisation Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 0301040R0AAAAAA (BNF code) | Salbutamol/Ipratropium inhaler 100/20 (200 doses) | Not specified | Not specified |
The record holds one valid single-ingredient authorisation. The number shown appears to be a BNF-style code (BNF section 3.1.4, antimuscarinic bronchodilators) rather than an MHRA PL number. No dosage form, manufacturer or indication text is recorded, so this should be checked against the MHRA register.
Safety Considerations
Contraindications and cautions from the knowledge graph (these come from drug-disease links, not from label text, and should be checked against the SmPC):
- Cardiovascular: hypertension, long QT syndrome, sudden cardiac arrest, heart conduction disease, myocardial ischaemia, coronary artery disease
- Metabolic and endocrine: diabetes mellitus, diabetic ketoacidosis, metabolic acidosis, potassium deficiency, hyperthyroidism (including Graves disease)
- Eye and urinary: angle-closure glaucoma, ocular hypertension, benign prostatic hyperplasia, bladder neck obstruction
- Neurological: epilepsy
Many of these probably reflect the salbutamol component of the combination product.
Drug interactions: 106 interactions were identified. The 20 listed in the data are all moderate. They are mostly other anticholinergic or antimuscarinic agents, including hyoscyamine, atropine, glycopyrronium, scopolamine, trospium and aclidinium. These carry additive anticholinergic effects. Other listed agents include promethazine, chlorpheniramine, prucalopride, eluxadoline and inhaled insulin.
Other signals in the literature: a case report describes severe anaphylaxis after ipratropium inhalation, and another describes unilateral mydriasis after inhalation.
Please refer to the SmPC and BNF for full safety information. Report suspected adverse reactions via the Yellow Card Scheme.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Ipratropium and ipratropium/salbutamol are well established in COPD, and at least one large completed Phase 3 trial (NCT02177253, n=1118) supports the combination. The prediction overlaps with existing use, so it adds little new. Evidence is therefore strong but not novel, and the record lacks UK indication and safety label data.
To proceed, the following is needed:
- The MHRA marketing authorisation details (PL number, dosage form and approved indication) for the product concerned
- SmPC warnings and contraindications to replace the knowledge-graph signals
- Mechanism of action data
- Confirmation of whether any new use beyond existing COPD labelling is intended
- Review of the NICE and BNF guidance on place in therapy
Other Predicted Indications (for context)
| Rank | Predicted Indication | Score | Evidence Level | Suggested Decision | |—|—|—|—|—| | 2 | Nasal cavity disease | 99.86% | L4 | Research question (a meta-analysis of intranasal anticholinergics in chronic rhinitis exists, but no trials in this dataset) | | 3 | Pharyngitis | 99.85% | L4 | Hold (weak, speculative rationale) | | 4 | Acute laryngopharyngitis | 99.84% | L5 | Hold (model prediction only) | | 5 | Respiratory malformation | 99.80% | L3 | Research question (small, mislabelled evidence) | | 6 | Papillary conjunctivitis | 99.75% | L5 | Hold (ocular exposure can cause mydriasis) | | 7 | Rienhoff syndrome | 99.69% | L5 | Hold (model prediction only) | | 8 | Tracheal disease | 99.66% | L4 | Research question (preclinical evidence only) | | 9 | Anaphylaxis | 99.38% | L4 | Hold (a case report shows the drug can trigger anaphylaxis) | | 10 | Food-dependent exercise-induced anaphylaxis | 99.36% | L5 | Hold (model prediction only) |
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.