Ipratropium
| Evidence Level: L5 | Predicted Indications: 9 |
Table of Contents
Ipratropium: Nasal cavity disease
One-Sentence Summary
Ipratropium is an inhaled anticholinergic (muscarinic antagonist) bronchodilator, originally used for chronic obstructive pulmonary disease (COPD), allergic and vasomotor rhinitis, bronchitis and related airway conditions. with 25 clinical trials and 20 publications retrieved for this prediction. This is largely a confirmation of its established use rather than true repurposing, because the predicted indication overlaps heavily with the existing COPD, emphysema and bronchial disease indications.
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 |
| India Market Status | Listed in a compiled Indian medicine price dataset (8 of 8) – CDSCO approval status is not included in this data |
| Number of Listed Products | 8 (valid: 8) |
| 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 that blocks cholinergic (vagally mediated) bronchoconstriction in airway smooth muscle. Review articles in the retrieved literature describe it as a non-selective muscarinic receptor antagonist delivered by inhalation.
These are conditions for which ipratropium is already used. The mechanism is therefore the same as that behind the existing use, and the prediction mostly reflects the established role of the drug in airway obstruction.
Other top predictions (nasal cavity disease, pharyngitis, tracheal disease and others) are supported by far weaker evidence. They are not the focus of this report, but they are summarised in the conclusion.
Clinical Trial Evidence
The compiled data contain 25 trials. The most relevant are listed below, prioritising completed, larger and directly relevant studies.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02177253 | Phase 3 | Completed | 1118 | 12-week study comparing ipratropium/salbutamol via Respimat with COMBIVENT aerosol, ipratropium Respimat and placebo in COPD (bronchodilator efficacy and safety) |
| NCT01415518 | Phase 4 | Completed | 581 | Symbicort added to Atrovent plus theophylline versus Atrovent plus theophylline in severe COPD |
| NCT02172469 | Phase 3 | Completed | 215 | Tiotropium 18 µg versus Atrovent MDI in COPD |
| NCT00239434 | Phase 3 | Completed | 200 | Once-daily tiotropium versus Atrovent MDI four times daily in COPD |
| NCT00371527 | NA | Completed | 200 | Randomised, double-blind, placebo-controlled trial of ipratropium for symptom control in acute bronchitis without underlying lung disease |
| NCT02172404 | Phase 3 | Completed | 160 | HandiHaler versus MDI administration technique in COPD (device usability, not efficacy) |
| NCT01136421 | Phase 3 | Completed | 124 | Magnesium sulfate versus ipratropium bromide, each with a short-acting β2 agonist, in acute COPD exacerbation |
| NCT01691482 | Phase 4 | Completed | 56 | 4-week crossover of albuterol and ipratropium, alone and combined, in COPD |
| NCT06918418 | Phase 4 | Completed | 60 | Salbutamol alone versus salbutamol plus ipratropium in children with acute asthma |
| NCT02686086 | NA | Completed | 60 | Lung volumes and symptom scores after bronchodilator via vibrating mesh versus jet nebuliser in COPD |
Several other registered trials were withdrawn or terminated with 0–3 participants and provide no usable evidence (for example NCT02235428, NCT04446637).
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 26391969 | 2015 | Systematic review | Cochrane Database Syst Rev | Tiotropium versus ipratropium bromide in stable COPD |
| 35616126 | 2022 | Systematic review | Cochrane Database Syst Rev | Magnesium sulfate as an adjunct in COPD exacerbations (bronchodilator context) |
| 23170031 | 2012 | Review | Ann Pharmacother | Efficacy and safety of ipratropium combined with tiotropium in COPD |
| 20163324 | 2010 | Review | Expert Opin Drug Metab Toxicol | Mechanism, efficacy and safety of albuterol, ipratropium and their combination in COPD |
| 25515181 | 2015 | Guideline | Basic Clin Pharmacol Toxicol | Finnish guideline on diagnosis and pharmacotherapy of stable COPD |
| 38457591 | 2024 | Retrospective study | Medicine | Probiotics added to budesonide and ipratropium in 118 COPD patients: lung function and gut microbiota |
| 10565879 | 1999 | Review | Respir Care Clin N Am | Ipratropium described as a safe and effective bronchodilator in COPD, alone and with albuterol |
| 2977109 | 1988 | Review | Clin Pharm | Pharmacology, pharmacokinetics, efficacy and adverse effects of ipratropium in obstructive lung disease |
| 15987237 | 2005 | Review | Treat Respir Med | Ipratropium HFA inhaler for maintenance treatment of bronchospasm |
| 11249465 | 2000 | Review | Expert Opin Pharmacother | Anticholinergic bronchodilators used in combination for COPD |
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 110430 | Ipramist 250mcg Inhaler (Zydus Cadila) | Packet of 200 MDI inhaler | Not stated |
| 107746 | Ipravent Respules 2ml (Cipla) | Strip of 5 respules | Not stated |
| 107959 | Ipravent Rotacaps (Cipla) | Packet of 30 capsules (for inhalation) | Not stated |
| 109544 | Ipratop 200mcg Inhaler (AstraZeneca) | Packet of 1 inhaler | Not stated |
| 109655 | Ipramist 250mcg Solution for inhalation (Zydus Cadila) | Bottle of 15 ml solution for inhalation | Not stated |
There are 8 valid single-ingredient registrations in total and no cancelled ones. Three more are not shown above: 13891 (Aprovent Inhaler, Cipla), 108961 (Ipneb Solution for inhalation, Lupin) and 107821 (Ipravent Respirator Solution, Cipla).
Safety Considerations
Drug interactions: The interaction screen identified 106 potential interactions. All of those listed in the compiled data are rated Moderate. They are mainly additive anticholinergic effects with other antimuscarinic agents, such as hyoscyamine, atropine, glycopyrronium, scopolamine, trospium, dicyclomine and aclidinium. Other examples include promethazine, chlorpheniramine, prucalopride, eluxadoline and inhaled insulin.
Conditions flagged in the knowledge graph (not label text): The drug-disease contraindication data list the following conditions, which should be checked carefully before use:
- Angle-closure glaucoma and ocular hypertension
- Benign prostatic hyperplasia and bladder neck obstruction
- Long QT syndrome, heart conduction disease, sudden cardiac arrest, myocardial ischaemia and coronary artery disease
- Hypertension
- Epilepsy
- Hyperthyroidism, Graves disease and thyrotoxicosis
- Diabetes mellitus, diabetic ketoacidosis, acidosis and potassium deficiency
Additional signals from the literature: One case report describes severe anaphylaxis after ipratropium inhalation, and another describes unilateral mydriasis (pupil dilation) after inhalation in an infant.
Package-insert warnings and contraindications for the Indian products were not available, so please refer to the package insert for the official safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Several large Phase 3 and Phase 4 trials in COPD and a substantial body of review literature support ipratropium in obstructive lung disease, and the drug is already marketed in India under 8 registrations. The prediction largely confirms existing use rather than opening a new indication, so the evidence is strong but the novelty is low.
Other predictions (not recommended to proceed at this time):
- Nasal cavity disease: overlaps with the existing rhinitis use; evidence is indirect, with only a preclinical hydrogel study and no trials. Research question.
- Respiratory malformation and tracheal disease: only small or preclinical support. Research question.
- Pharyngitis, acute laryngopharyngitis, papillary conjunctivitis, Rienhoff syndrome and food-dependent exercise-induced anaphylaxis: little or no direct evidence. Hold.
- Anaphylaxis: Hold, because epinephrine is the standard of care and there is a case report of anaphylaxis caused by ipratropium.
To proceed, the following is needed:
- Package-insert warnings, contraindications and approved-indication text for the Indian products (a blocking gap for safety screening)
- Detailed mechanism-of-action data from DrugBank
- A safety monitoring plan for patients with glaucoma, urinary retention or prostatic hyperplasia, and cardiac conditions
- Confirmation that the pending trial relevance assessments do not change the evidence grading
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.