Ipratropium

Evidence Level: L5

Predicted Indications: 9

Ipratropium

Pharmacist Assessment Report

Ipratropium: Nasal cavity disease

One-Sentence Summary

Ipratropium is an inhaled anticholinergic bronchodilator originally used for chronic obstructive pulmonary disease (COPD), rhinitis, bronchitis and related airway conditions. This prediction largely overlaps with the existing COPD use, so it is closer to on-label use than true repurposing.

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
Canada Market Status	Marketed (marketed DINs: 12 of 12)
Number of DINs	12 (marketed: 12)
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Ipratropium is a muscarinic receptor antagonist. It blocks muscarinic receptors on airway smooth muscle, which reduces cholinergic (vagal) bronchoconstriction and mucus secretion. Detailed mechanism-of-action data was not available in the data compiled for this report, but the published reviews describe this as the established mechanism.

COPD is itself a form of obstructive lung disease. The predicted indication therefore sits within the drug’s existing use rather than outside it. Asthma, acute exacerbations and COPD all involve airway narrowing that is partly driven by cholinergic tone, which is why anticholinergics are used alone or combined with salbutamol (a beta-agonist).

Clinical Trial Evidence

The compiled data contains 25 trials for this indication. The most relevant are listed below.

Trial Number	Phase	Status	Enrollment	Key Findings
NCT02177253	Phase 3	Completed	1118	12-week study comparing ipratropium/salbutamol via Respimat with Combivent aerosol, ipratropium alone and placebo in COPD
NCT01136421	Phase 3	Completed	124	Magnesium sulfate vs ipratropium (each with a short-acting beta-agonist) in acute COPD exacerbation
NCT02172469	Phase 3	Completed	215	Tiotropium vs Atrovent MDI in COPD, bronchodilator efficacy and safety
NCT00239434	Phase 3	Completed	200	Once-daily tiotropium vs Atrovent MDI four times daily in COPD
NCT02172404	Phase 3	Completed	160	HandiHaler vs MDI: administration technique and ease of use in COPD (device-focused, not efficacy)
NCT02686086	N/A	Completed	60	Lung volume and symptom scores after bronchodilator via vibrating mesh vs jet nebuliser in COPD
NCT01415518	Phase 4	Completed	581	Symbicort added to Atrovent plus theophylline vs Atrovent plus theophylline in severe COPD
NCT06918418	Phase 4	Completed	60	Salbutamol alone vs salbutamol plus ipratropium in children with acute asthma
NCT04446637	Phase 3	Withdrawn	0	Ipratropium/levosalbutamol fixed-dose combination in COPD; no participants enrolled
NCT02235428	Phase 4	Terminated	3	Ipratropium added to high-dose salbutamol in young children with acute asthma; too small to inform efficacy

Literature Evidence

PMID	Year	Type	Journal	Key Findings
35616126	2022	Review (Cochrane)	Cochrane Database Syst Rev	Magnesium sulfate as an adjunct in COPD exacerbations
29578103	2018	RCT	Respir Physiol Neurobiol	Acute bronchodilators did not reduce wasted ventilation during exercise in 20 COPD patients
23170031	2012	Review	Ann Pharmacother	Efficacy and safety of ipratropium used together with tiotropium in COPD
26391969	2015	Review (Cochrane)	Cochrane Database Syst Rev	Tiotropium vs ipratropium in stable COPD (update)
24043433	2013	Review (Cochrane)	Cochrane Database Syst Rev	Tiotropium vs ipratropium in stable 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 as an effective, safe bronchodilator, alone and with albuterol
2977109	1988	Review	Clin Pharm	Pharmacology, efficacy, adverse effects and dosing of ipratropium in obstructive lung disease
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, assessing lung function and gut microbiota

Canada Market Information

Twelve licences are valid in Canada. Dosage form and approved-indication text were not available in the records compiled for this report. The main products are:

DIN	Product Name	Dosage Form	Approved Indication
02247686	ATROVENT HFA	Not available	Not available
02216221	TEVA-IPRATROPIUM STERINEBS	Not available	Not available
02231245	PMS-IPRATROPIUM	Not available	Not available
02419106	COMBIVENT RESPIMAT	Not available	Not available
02542587	JAMP IPRATROPIUM HFA	Not available	Not available

Other licences include AA-IPRAVENT, IPRAVENT, TEVA-COMBO STERINEBS and an ipratropium/salbutamol inhalation solution. Several of these are combination-type products registered as single entries.

Safety Considerations

Disease contraindication signals (knowledge graph, not label text): The graph links ipratropium to caution in angle-closure glaucoma, benign prostatic hyperplasia and bladder neck obstruction, which fit anticholinergic effects. It also lists cardiovascular conditions (hypertension, long QT syndrome, myocardial ischaemia, coronary artery disease, sudden cardiac arrest, heart conduction disease), diabetes and diabetic ketoacidosis, hyperthyroidism, epilepsy, potassium deficiency and metabolic acidosis. Some of these probably reflect the salbutamol component of combination products. They should be confirmed against the approved labelling.
Drug interactions: 100 interactions were found, all of Moderate level among those shown. Most involve other anticholinergic or antimuscarinic agents (atropine, hyoscyamine, glycopyrronium, scopolamine, dicyclomine, trospium, aclidinium), with additive anticholinergic effects. Others include promethazine, chlorpheniramine, eluxadoline, prucalopride and inhaled insulin.
Case reports in the literature: Severe anaphylaxis after inhaled ipratropium (PMID 8449120) and unilateral mydriasis after inhalation in an infant (PMID 40069469).

Please refer to the package insert for the full warnings and contraindications.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Several large, completed Phase 3 trials, including one with 1,118 COPD participants, plus Cochrane reviews support ipratropium as a bronchodilator in obstructive airway disease. Because this overlaps with its approved COPD use, the case is strong but is closer to on-label use than to new repurposing. The evidence level of L1 should be read cautiously: many trials are active-comparator or device studies, and the data contains no placebo-controlled efficacy summary specific to ipratropium alone.

To proceed, the following is needed:

Canadian package insert warnings, contraindications and approved-indication text, which are missing from the compiled data
Detailed mechanism-of-action data from DrugBank
A clear definition of the target population within “obstructive lung disease” (COPD vs asthma, adult vs paediatric)
A review of the anticholinergic and cardiovascular safety signals, especially in patients with glaucoma, prostatic or bladder outlet obstruction, or heart rhythm disorders

Other Predicted Indications (for reference)

Rank	Predicted Indication	Evidence Level	Recommendation	Note
2	Nasal cavity disease	L5	Research Question	Consistent with the known rhinitis use, but the retrieved studies are indirect or preclinical
3	Pharyngitis	L5	Hold	No study tests ipratropium in pharyngitis
4	Acute laryngopharyngitis	L5	Hold	Prediction only
5	Respiratory malformation	L5	Hold	Evidence is indirect
6	Papillary conjunctivitis	L5	Hold	Prediction only
7	Rienhoff syndrome	L5	Hold	Prediction only
8	Tracheal disease	L4	Hold	Preclinical and mechanistic work only
9	Anaphylaxis	L4	Hold	Preclinical only, and one case report of anaphylaxis caused by ipratropium
10	Food-dependent exercise-induced anaphylaxis	L5	Hold	Prediction only

Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.