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Continuing Education Activity

Ipratropium is a bronchodilator medication that dilates the airways of the lungs. Ipratropium has been approved by the US Food and Drug Administration (FDA) for treating bronchospasms associated with chronic obstructive pulmonary disease (COPD), including emphysema and chronic bronchitis. Maintenance therapy with ipratropium has established benefits in the treatment of COPD. Understanding the broad-spectrum therapeutic potential of ipratropium, including its FDA-approved indications for bronchospasms associated with COPD and off-label uses for asthma exacerbations and rhinorrhea, is crucial.

Incorporating ipratropium alongside short-acting beta-agonists in managing severe asthma exacerbations and utilizing its nasal spray formulation for symptomatic relief of rhinorrhea associated with the common cold or allergic rhinitis highlights its versatility in clinical practice. The diverse formulations, such as nasal spray, metered-dose inhaler, and nebulized solution, allow customized treatment approaches across different patient populations. This activity reviews the indications, mechanism of action, administration, drug interactions, and adverse reactions of ipratropium, highlighting the importance of interprofessional healthcare teams involving clinicians, pharmacists, and pulmonologists to ensure effective ipratropium therapy. This activity also fosters collaborative practice among healthcare professionals, enabling them to enhance their understanding and utilization of ipratropium through shared decision-making, thereby contributing toward improved patient outcomes in respiratory care.


  • Identify appropriate indications for ipratropium therapy, including its FDA-approved uses for chronic obstructive pulmonary disease exacerbations and off-label applications such as asthma exacerbations and rhinorrhea.

  • Implement evidence-based guidelines for ipratropium dosing and administration in chronic obstructive pulmonary disease exacerbations and other respiratory conditions.

  • Select the most appropriate ipratropium formulation and dosage regimen to tailor treatment plans based on patient characteristics and clinical presentation.

  • Collaborate with interprofessional healthcare teams, including pharmacists and pulmonologists, to ensure coordinated ipratropium therapy and comprehensive patient care.


Ipratropium is a bronchodilator medication that dilates the airways of the lungs. Ipratropium has been approved by the US Food and Drug Administration (FDA) for treating bronchospasms associated with chronic obstructive pulmonary disease (COPD), including emphysema and chronic bronchitis. Maintenance therapy with ipratropium has established benefits in the treatment of COPD. 

Off-label uses of ipratropium include asthma exacerbations and clearance of secretions, especially in intubated patients in the intensive care unit (ICU).[1] 

As per the National Heart, Lung, and Blood Institute (NHLBI) recommendations, short-acting beta-agonists (SABA) combined with inhaled ipratropium is endorsed for managing severe asthma exacerbations. Incorporating ipratropium alongside multiple doses of SABA in managing moderate-to-severe asthma exacerbations within the emergency department provides additional benefits, particularly for patients with more pronounced airway obstruction.[2]

Ipratropium nasal spray (0.06%) formulation is FDA-approved to provide symptomatic relief for rhinorrhea in adults and children (age 5 and older) associated with the common cold or seasonal allergic rhinitis. The medication does not control nasal congestion or sneezing related to these conditions. According to the FDA, extended use beyond 4 days for the common cold or 3 weeks for seasonal allergic rhinitis lacks established safety and effectiveness.[3] 

Off-label uses of ipratropium nasal spray include non-allergic rhinitis. According to a recent meta-analysis, ipratropium nasal spray has demonstrated both safety and efficacy in managing rhinorrhea associated with non-allergic rhinitis, significantly reducing its severity and duration.[4]

According to the Global Initiative for Asthma (GINA) guidelines, patients should be transferred to an acute care facility or ICU, mainly if they exhibit altered mental status or a silent chest. During the transfer, it is recommended to administer SABA and ipratropium, along with oxygen and systemic steroids. Vital signs, oxygen saturation, and pulmonary function should be closely monitored. Ipratropium is indicated for severe exacerbations.[5]

According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, SABA, with or without short-acting anticholinergics (SAMA) such as ipratropium, are the initial bronchodilators recommended for acute treatment of exacerbation of COPD along with supportive measures.[6]

Mechanism of Action

Ipratropium is an acetylcholine antagonist via the blockade of muscarinic cholinergic receptors. Blocking cholinergic receptors decreases the production of cyclic guanosine monophosphate (cGMP). This decrease in the lung airways leads to decreased contraction of the smooth muscles. The M2 receptors are situated at the terminals of cholinergic nerve endings and function as feedback regulators, inhibiting acetylcholine release. When these receptors are blocked, it results in an increased release of acetylcholine and an increased bronchoconstrictor response to cholinergic nerve stimulation.

Ipratropium acts as a nonselective blocker, which also blocks the M2 receptors, leading to an increase in acetylcholine release and a reduction in the extent or duration of action on the M3 receptors. This may explain the reported occurrence of paradoxical bronchoconstriction following the use of ipratropium.[7] The actions of intranasal ipratropium mimic the action of atropine by inhibiting salivary and mucous gland secretions and dilating bronchial smooth muscle. Compared to atropine, orally inhaled ipratropium is a more potent antimuscarinic and bronchial smooth muscle dilator.

Intranasal ipratropium produces a local parasympathetic response, decreasing water secretions of the nasal system's mucosal glands and alleviating rhinorrhea symptoms (allergic or non-allergic).[1] Studies showed that the mean peak percent increases in FEV1 over baseline were 24% to 25% for oral inhaled ipratropium in COPD patients. The research noted similar changes in forced vital capacity (FVC) curves. However, when given via metered-dose inhaler to patients with COPD, the combination of ipratropium and albuterol proved more effective than the 2 agents alone.[8]


Absorption: Ipratropium is deposited in the gastrointestinal tract after administration, while a smaller portion reaches the lung, its intended site of action. Systemic absorption is poor due to its quaternary amine nature. The time to pulmonary function improvement (FEV1 increase of 15% or more) is approximately 15 minutes, peak plasma concentration achieved in 1 to 2 hours, and duration of action persists for 2 to 4 hours. For ipratropium nasal formulation, systemic absorption is less than 20%, and the onset of action is approximately 15 minutes.

Distribution: Ipratropium exhibits minimal binding (0% to 9%) to plasma albumin and α1-acid glycoprotein. The quaternary ammonium structure hinders the ability to cross lipid membranes, including the blood-brain barrier. [9]

Metabolism: Ipratropium undergoes partial metabolism, resulting in inactive ester hydrolysis products.[10]

Elimination: Following inhalation or intravenous administration, the elimination half-life of ipratropium is approximately 2 hours. Around 50% of the dose is excreted unchanged in the urine.


Available Dosage Forms and Strengths

Ipratropium is available as a nasal spray (0.03% and 0.06%), a metered-dose inhaler (17 mcg per actuation), and a nebulized solution (0.02%). The fixed-dose combination of albuterol and ipratropium is available as an aerosol metered-dose inhaler with dosages of 100 mcg of albuterol and 20 mcg of ipratropium per actuation for managing COPD. The fixed-dose combination of albuterol and ipratropium is also available as a nebulizer solution (2.5 mg albuterol and 0.5 mg ipratropium per 3 mL).

The administration of ipratropium is via inhalation, either orally or intranasally. The diverse formulations, such as nasal spray, metered-dose inhaler, and nebulized solution, allow customized treatment approaches across different patient populations. 

Oral inhalation: The oral formulation is aerosol inhalation or a solution for nebulization.

Aerosol inhalation: If the patient experiences difficulty inhaling the drug after actuation, they can use a valved holding chamber (VHC) or a spacer. A patient can choose between a mouthpiece or a face mask along with the VHC or spacer based on patient convenience. Usually, it is more convenient for patients under 4 to use a tight face mask and VHC or spacer. The patient should be instructed to inhale 3 to 5 times per actuation when using a face mask. After administration, the patient is advised to rinse the mouth with water to decrease the adverse effect of mouth dryness. Patients should not use non-prescribed inhalers to prevent the transfer of any possible infections.[11]

Ipratropium Dosages

Adult dosages: Adult dosages are mentioned below.

  • 17 mcg per spray
  • COPD: 2 sprays every 6 hours
  • Asthma exacerbation, moderate-to-severe: 8 sprays every 20 minutes as needed for up to 3 hours.

Pediatric dosages: Pediatric dosages are mentioned below.

  • NEB (0.02%): 0.25 mg every 20 mins up to 3 doses for moderate-to-severe asthma exacerbation for patients aged 6 and younger.
  • NEB (0.02%): 0.25 mg to 0.5 mg every 20 mins as needed up to 3 hours for moderate-to-severe asthma exacerbation in patients aged 6 through 12.
  • NEB (0.02%): 0.5 mg every 20 mins as needed up to 3 hours for moderate-to-severe asthma exacerbation for patients aged 13 or older.

Solution for Nebulization

Ipratropium can be mixed with albuterol formations in the same nebulizer within 1 hour of use. However, it should not be combined with cromolyn solutions, as both are incompatible.

Intranasal Inhalation

When using the nasal spray solution for intranasal inhalation, it is important to adhere to the below-mentioned points.

  • Nasal spray solution:
    • Prime the unit before using it for the first time.
    • Point the sprayer away from patients, other persons, or animals.
    • Push the activator 6 to 7 times until a wide and fine spray is observed.
    • After that, if the unit remains unused for over 24 hours, prime the unit again by pushing the pump at least twice before use. If the unit remains unused for over 7 days, prime the team by pushing the pump 7 times.
    • Patients should be instructed not to use other inhalers to prevent the transfer of any possible infections.[8]
  • Dosage:
    • 0.03% solution: 21 mcg/spray
    • 0.06% solution: 42 mcg/spray
    • Rhinorrhea (allergic or nonallergic rhinitis): 2 sprays of 0.03% solution per nostril every 6 hours. Seasonal allergic rhinitis: 2 sprays of 0.06% per nostril every 6 or 8 hours.
    • Common cold: 2 sprays of 0.06% per nostril every 6 hours or every 8 hours

COPD exacerbation: According to GOLD guidelines, SABA, with or without SAMA (such as ipratropium), is the initial bronchodilator recommended for acute treatment of exacerbation of COPD along with supportive measures.[6]

Asthma exacerbation: According to the GINA guidelines, patients should be transferred to the medical ICU, particularly if they exhibit altered mental status or a silent chest. During the transfer, it is recommended to administer SABA and ipratropium, along with oxygen and systemic steroids. Vital signs, oxygen saturation, and pulmonary function should be closely monitored. Ipratropium should be administered for severe exacerbations.[5] 

Specific Patient Populations

Hepatic impairment: The effects of ipratropium in patients with hepatic insufficiency have not been investigated.

Renal impairment: The effects of ipratropium in patients with renal insufficiency have not been investigated.

Pregnancy considerations: Ipratropium was previously categorized as FDA pregnancy category B due to the absence of reports regarding teratogenic effects in animals or humans following the use of ipratropium (aerosols or nasal spray); however, human studies are limited.[1] Ipratropium is considered safe during pregnancy and can be utilized in acute asthma attacks, causing minimal tachycardic effects on both the mother and fetus.[12]

Breastfeeding considerations: Ipratropium administration results in minimal maternal serum levels, and the infant is unlikely to absorb any drug present in breast milk. Therefore, the risk to the breastfed baby from maternal ipratropium use is minimal.[13]

Pediatric patients: Ipratropium nasal spray is not FDA-approved for use in patients aged 5 and younger.

Older patients: The pharmacokinetics of ipratropium nasal spray have not been investigated in older patients. The effectiveness of ipratropium (metered-dose inhaler) has been demonstrated to be comparable for patients both younger and older than 65. Moreover, no differences in safety or effectiveness have been observed between older and younger patients. According to the American Geriatric Society Beers Criteria, assessing the total anticholinergic burden is recommended.[14]

Adverse Effects

Ipratropium Inhaled

Most common adverse reactions:

  • Xerostomia
  • Skin flushing
  • Dyspnea
  • Symptoms of a common cold
  • Dizziness
  • Sinusitis
  • Dyspepsia
  • Back pain
  • UTI
  • Tachycardia
  • Bronchitis
  • Nausea[15]

Ipratropium Intranasal

Most common adverse reactions:

  • Upper respiratory infections
  • Epistaxis
  • Pharyngitis
  • Headache
  • Xerostomia
  • Dysgeusia
  • Nausea
  • Nasal irritation
  • Arrhythmias

Severe adverse reactions[16]:

  • Hypersensitivity reaction
  • Anaphylaxis
  • Arrhythmias, including exacerbation of atrial flutter and atrial fibrillation (AHA)[17]

Drug-Drug Interactions[18]

Ipratropium may interact with medications from the following classes that have anticholinergic activity:

  • Revefenacin and aclidinium
  • Antidepressants (eg, amitriptyline, paroxetine)
  • Antihistamines (eg, diphenhydramine, hydroxyzine, chlorpheniramine)
  • Agents for overactive bladder (eg, darifenacin, oxybutynin, solifenacin)
  • Anti-parkinson agents (eg, benztropine, trihexyphenidyl)
  • Antipsychotics (eg, olanzapine, quetiapine, haloperidol)
  • Cardiovascular agents (eg, disopyramide)
  • Atropine and hyoscyamine
  • Muscle relaxants such as cyclobenzaprine


Contraindications to ipratropium inhaler use include patients with hypersensitive to ipratropium bromide or atropine due to the structural similarity between ipratropium bromide and atropine.[19]

Warning and Precautions

Ipratropium aerosols can cause bronchospasms (paradoxical), which usually happen upon the initial use of this medication. If this adverse reaction occurs, then ipratropium should be immediately discontinued.[20] Previous severe allergic reaction symptoms upon using ipratropium or atropine and its other derivatives, such as angioedema, urticaria, severe shortness of breath, oropharyngeal edema, and ultimately anaphylaxis is a contraindication to ipratropium use. Concomitant allergies may be present.[21] Caution is necessary for using intranasal or inhaled ipratropium in patients with benign prostatic hyperplasia (BPH).[22] Exercise caution with intranasal or inhaled ipratropium in patients with obstruction of the bladder neck. Caution is also recommended in intranasal or inhaled ipratropium in patients with closed-angle glaucoma.[1]


Ipratropium inhalation aerosol is a bronchodilator agent for chronic control of bronchospasms secondary to COPD, not a first-line medication for acute bronchospasm, and not used as a rapid response agent for acute situations. Symptoms of anaphylaxis (angioedema, urticaria, bronchospasms, and rash) should be monitored, primarily upon the first use of this medication. As mentioned above, the drug should be discontinued if these symptoms occur.[23] Caution is necessary for patients with prostatic hypertrophy, bladder neck obstruction, and closed-angle glaucoma.[24] No routine monitoring tests are recommended; however, clinicians may order pulmonary function tests if necessary to assess the response to therapy.


High doses of ipratropium can cause toxicity similar to anticholinergic toxicity symptoms.[25][26]

These symptoms include hyperthermia, agitation, confusion, mydriasis, and mucosal dryness. Reports have indicated that ipratropium exacerbates ischemic injuries in nonclinical settings.

Enhancing Healthcare Team Outcomes

Ipratropium is a bronchodilator widely used for COPD. This drug is known to relieve bronchospasms and enhance the patency of the airways in the lungs. Prescribing this medication requires proper communication between clinicians, pharmacists, and subspecialty doctors such as pulmonologists. An interprofessional approach can effectively monitor drug efficacy and adjust the dosing and combination of this agent with other agents acting on the airways. However, most of the situations are manageable by one clinician. This medication can sometimes work with other agents acting on the airways. Still, it could be incompatible with other agents using the same nebulizer in some instances. Hence, it is essential to obtain drug-drug interactions via pharmacists.

Documenting any previous adverse reaction if this medication was used before, such as hypersensitivity reactions or anaphylaxis, is critical. Pharmacists should flag a prescription if those adverse reactions have been previously charted and immediately notify the clinicians and patients.[16] The successful implementation of ipratropium therapy requires an interprofessional team approach, including physicians, specialists, specialty-trained nurses, and pharmacists collaborating across disciplines to achieve optimal patient results.



Preeti Patel


Hussien Saab


Ayham Aboeed


2/19/2024 1:41:42 PM



Massey KL, Gotz VP. Ipratropium bromide. Drug intelligence & clinical pharmacy. 1985 Jan:19(1):5-12     [PubMed PMID: 3155676]


Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis. Thorax. 2005 Sep:60(9):740-6     [PubMed PMID: 16055613]

Level 1 (high-level) evidence


Kim KT, Kerwin E, Landwehr L, Bernstein JA, Bruner D, Harris D, Drda K, Wanger J, Wood CC, Pediatric Atrovent Nasal Spray Study Group. Use of 0.06% ipratropium bromide nasal spray in children aged 2 to 5 years with rhinorrhea due to a common cold or allergies. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2005 Jan:94(1):73-9     [PubMed PMID: 15702820]


El Khoury P, Abou Hamad W, Khalaf MG, El Hadi C, Assily R, Rassi S, Khoueir N. Ipratropium Bromide Nasal Spray in Non-Allergic Rhinitis: A Systematic Review and Meta-Analysis. The Laryngoscope. 2023 Dec:133(12):3247-3255. doi: 10.1002/lary.30706. Epub 2023 Apr 17     [PubMed PMID: 37067019]

Level 1 (high-level) evidence


Reddel HK, Bacharier LB, Bateman ED, Brightling CE, Brusselle GG, Buhl R, Cruz AA, Duijts L, Drazen JM, FitzGerald JM, Fleming LJ, Inoue H, Ko FW, Krishnan JA, Levy ML, Lin J, Mortimer K, Pitrez PM, Sheikh A, Yorgancioglu AA, Boulet LP. Global Initiative for Asthma Strategy 2021: Executive Summary and Rationale for Key Changes. American journal of respiratory and critical care medicine. 2022 Jan 1:205(1):17-35. doi: 10.1164/rccm.202109-2205PP. Epub     [PubMed PMID: 34658302]


Agustí A, Celli BR, Criner GJ, Halpin D, Anzueto A, Barnes P, Bourbeau J, Han MK, Martinez FJ, Montes de Oca M, Mortimer K, Papi A, Pavord I, Roche N, Salvi S, Sin DD, Singh D, Stockley R, López Varela MV, Wedzicha JA, Vogelmeier CF. Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary. American journal of respiratory and critical care medicine. 2023 Apr 1:207(7):819-837. doi: 10.1164/rccm.202301-0106PP. Epub     [PubMed PMID: 36856433]


Scullion JE. The development of anticholinergics in the management of COPD. International journal of chronic obstructive pulmonary disease. 2007:2(1):33-40     [PubMed PMID: 18044064]


. In chronic obstructive pulmonary disease, a combination of ipratropium and albuterol is more effective than either agent alone. An 85-day multicenter trial. COMBIVENT Inhalation Aerosol Study Group. Chest. 1994 May:105(5):1411-9     [PubMed PMID: 8181328]

Level 1 (high-level) evidence


. Ipratropium. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012:():     [PubMed PMID: 31643978]


Chen Y, Du S, Zhang Z, He W, Lu E, Wang R, Sha X, Ma Y. Compatible Stability and Aerosol Characteristics of Atrovent(®) (Ipratropium Bromide) Mixed with Salbutamol Sulfate, Terbutaline Sulfate, Budesonide, and Acetylcysteine. Pharmaceutics. 2020 Aug 15:12(8):. doi: 10.3390/pharmaceutics12080776. Epub 2020 Aug 15     [PubMed PMID: 32824123]


Summers QA, Tarala RA. Nebulized ipratropium in the treatment of acute asthma. Chest. 1990 Feb:97(2):425-9     [PubMed PMID: 2137076]


Couillard S, Connolly C, Borg C, Pavord I. Asthma in pregnancy: An update. Obstetric medicine. 2021 Sep:14(3):135-144. doi: 10.1177/1753495X20965072. Epub 2020 Nov 1     [PubMed PMID: 34646341]


. Ipratropium. Drugs and Lactation Database (LactMed®). 2006:():     [PubMed PMID: 30000543]


By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society. 2023 Jul:71(7):2052-2081. doi: 10.1111/jgs.18372. Epub 2023 May 4     [PubMed PMID: 37139824]


Thornton CS, Haws JT. Bromism in the Modern Day: Case Report and Canadian Review of Bromide Intoxication. Journal of general internal medicine. 2020 Aug:35(8):2459-2461. doi: 10.1007/s11606-020-05907-x. Epub 2020 May 18     [PubMed PMID: 32424782]

Level 3 (low-level) evidence


Kopsaftis ZA, Sulaiman NS, Mountain OD, Carson-Chahhoud KV, Phillips PA, Smith BJ. Short-acting bronchodilators for the management of acute exacerbations of chronic obstructive pulmonary disease in the hospital setting: systematic review. Systematic reviews. 2018 Nov 29:7(1):213. doi: 10.1186/s13643-018-0860-0. Epub 2018 Nov 29     [PubMed PMID: 30497532]

Level 1 (high-level) evidence


Tisdale JE, Chung MK, Campbell KB, Hammadah M, Joglar JA, Leclerc J, Rajagopalan B, American Heart Association Clinical Pharmacology Committee of the Council on Clinical Cardiology and Council on Cardiovascular and Stroke Nursing. Drug-Induced Arrhythmias: A Scientific Statement From the American Heart Association. Circulation. 2020 Oct 13:142(15):e214-e233. doi: 10.1161/CIR.0000000000000905. Epub 2020 Sep 15     [PubMed PMID: 32929996]


Ajimura CM, Jagan N, Morrow LE, Malesker MA. Drug Interactions With Oral Inhaled Medications. The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians. 2018 Dec:34(6):273-280. doi: 10.1177/8755122518788809. Epub 2018 Jul 19     [PubMed PMID: 34861014]


. Drugs for asthma. The Medical letter on drugs and therapeutics. 2020 Dec 14:62(1613):193-200     [PubMed PMID: 33446622]

Level 3 (low-level) evidence


Gupta P, O'Mahony MS. Potential adverse effects of bronchodilators in the treatment of airways obstruction in older people: recommendations for prescribing. Drugs & aging. 2008:25(5):415-43     [PubMed PMID: 18447405]


Morfin-Maciel BM, Castillo-Morfin BM. [Angioedema and paradoxical bronchoconstriction secondary to ipratropium bromide/salbutamol administered by metered dose inhaler in patients with soy allergy]. Revista alergia Mexico (Tecamachalco, Puebla, Mexico : 1993). 2011 Oct-Dec:58(4):219-23     [PubMed PMID: 24007833]


Pras E, Stienlauf S, Pinkhas J, Sidi Y. Urinary retention associated with ipratropium bromide. DICP : the annals of pharmacotherapy. 1991 Sep:25(9):939-40     [PubMed PMID: 1835224]


Nezhinskaia GI, Vladykin AL, Sapronov NS. [Antianaphylactic effects of muscarinic antagonists]. Eksperimental'naia i klinicheskaia farmakologiia. 2010 May:73(5):27-9     [PubMed PMID: 20597367]


Ortiz Rambla J, Hidalgo Mora JJ, Gascón Ramón G, Navarro Arambudo B. [Acute angle-closure glaucoma and ipratropium bromide]. Medicina clinica. 2005 May 28:124(20):795     [PubMed PMID: 15927109]


Perkins MW, Wong B, Rodriguez A, Devorak JL, Alves DA, Murphy G, Sciuto AM. Inhalation toxicity of soman vapor in non-anesthetized rats: a preliminary assessment of inhaled bronchodilator or steroid therapy. Chemico-biological interactions. 2013 Dec 5:206(3):452-61. doi: 10.1016/j.cbi.2013.07.009. Epub 2013 Jul 23     [PubMed PMID: 23886498]


. Inhaled antimuscarinic drugs: cardiovascular toxicity. Prescrire international. 2010 Jun:19(107):122-3     [PubMed PMID: 20738041]