Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Aerosol Solution, Inhalation, as bromide:
Atrovent HFA: 17 mcg/actuation (12.9 g) [contains alcohol, usp]
Solution, Inhalation, as bromide:
Generic: 0.02% (2.5 mL)
Solution, Inhalation, as bromide [preservative free]:
Generic: 0.02% (2.5 mL)
Pharmacology
Mechanism of Action
Blocks the action of acetylcholine at parasympathetic sites in bronchial smooth muscle causing bronchodilation; local application to nasal mucosa inhibits serous and seromucous gland secretions.
Pharmacokinetics/Pharmacodynamics
Absorption
Not readily absorbed into the systemic circulation from the surface of the lung or from the GI tract; ~7% absorbed after nebulization of a 2 mg dose
Distribution
15% of dose reaches the lower airways
Metabolism
Partially metabolized to inactive ester hydrolysis products
Excretion
Urine (50%)
Onset of Action
Bronchodilation: Within 15 minutes; Peak effect: 1 to 2 hours
Duration of Action
Metered-dose inhaler: 2 to 4 hours; Nebulization solution: 4 to 5 hours, up to 7 to 8 hours in some patients
Half-Life Elimination
2 hours
Protein Binding
≤9%
Use: Labeled Indications
Chronic obstructive pulmonary disease: Maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema
Use: Off Label
Acute asthma (exacerbations)yesa
Based on the National Heart, Lung, and Blood Institute (NHLBI)/National Asthma Education and Prevention Program (NAEPP) guidelines, the use of ipratropium in combination with a short-acting beta-agonist (SABA), such as albuterol, is an effective and recommended treatment in the management of patients with asthma exacerbation. Controlled trials and a meta-analysis have demonstrated that the addition of ipratropium to SABA therapy in the management of moderate to severe acute asthma exacerbations has been associated with a decreased risk of hospitalization and an improvement in lung function.
Contraindications
Hypersensitivity to ipratropium, atropine (and its derivatives), or any component of the formulation
Dosage and Administration
Dosing: Adult
COPD: Inhalation:
Metered-dose inhaler (MDI): 2 inhalations (34 mcg) 4 times daily; maximum dose: 12 inhalations (204 mcg)/day
Nebulization solution: 0.5 mg (500 mcg, one unit-dose vial) every 6 to 8 hours
Acute asthma (exacerbations) (off-label use): Moderate to severe exacerbations:
Inhalation: Note: Should be given in combination with a short-acting beta-adrenergic agonist.
MDI: 8 inhalations (136 mcg) every 20 minutes as needed for up to 3 hours (NAEPP 2007)
Nebulization solution: 0.5 mg (500 mcg, one unit-dose vial) every 20 minutes for 3 doses, then as needed (NAEPP 2007)
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Asthma, acute exacerbation: Limited data available (GINA 2018; NAEPP 2007): Note: For moderate to severe exacerbations, ipratropium may be considered if poor response to initial short-acting beta-2 agonist (SABA) therapy during initial management in an acute care setting (eg, emergency department). Ipratropium has not been shown to provide further benefit (eg, after first 24 hours) once the patient is hospitalized (GINA 2018; Vézina 2014):
Children:
Nebulization: 0.25 to 0.5 mg (250 to 500 mcg) every 20 minutes for 1 hour (ie, 3 doses), then as needed; in trials, the usual reported dose is 0.25 mg (250 mcg) and reported interval range is every 1 to 8 hours typically with an increasing dosing interval as patient improves; some trials continued combination SABA/ipratropium therapy for duration of hospitalization (up to 49 hours) although trials have not demonstrated additional benefit with extended use (Vézina 2014)
Metered-dose inhaler: 4 to 8 puffs every 20 minutes as needed for up to 3 hours
Adolescents:
Nebulization: 0.5 mg (500 mcg) every 20 minutes for 3 doses, then as needed
Metered-dose inhaler: 8 puffs every 20 minutes as needed for up to 3 hours
Asthma, maintenance (nonacute): Limited data available: Note: Evidence is lacking that ipratropium provides added benefit to beta-2 agonists in long-term control asthma therapy (GINA 2018; NAEPP 2007):
Children <12 years:
Nebulization: 0.25 to 0.5 mg (250 to 500 mcg) every 6 to 8 hours
Metered-dose inhaler: 1 to 2 inhalations every 6 hours; not to exceed 12 inhalations/day
Children ≥12 years and Adolescents:
Nebulization: 0.25 to 0.5 mg (250 to 500 mcg) every 6 hours
Metered-dose inhaler: 2 to 3 inhalations every 6 hours; maximum daily dose: 12 inhalations/day
Bronchospasm associated with chronic pulmonary conditions: Children ≥12 years and Adolescents: Nebulization: 0.5 mg (500 mcg, one unit-dose vial) 3 to 4 times daily with doses 6 to 8 hours apart
Bronchospasm, wheezing: Limited data available; efficacy results variable: Infants: Nebulization: 0.125 to 0.25 mg (125 to 250 mcg) every 4 hours has been found helpful in some infants with chronic or recurrent wheezing, and some patients with bronchiolitis; however, most bronchiolitis data suggests ipratropium is not effective (Hodges 1981; Prendiville 1987; Schuh 1992; Stokes 1983; Wang 1992).
Administration
For oral inhalation; avoid spraying in eyes.
Metered-dose inhaler: Prior to initial use, prime inhaler by releasing 2 test sprays into the air; inhaler does not require shaking. If the inhaler has not been used for >3 days, reprime. Wash mouthpiece once a week for 30 seconds in warm water only and let air dry. Discard inhaler once dose indicator displays “0.”
Nebulization solution: Remove unit dose vial from foil pouch and squeeze contents into nebulizer reservoir; connect nebulizer to compressor. Breathe deeply and evenly until all medication has been inhaled; inhalation time is about 5 to 15 minutes. Clean nebulizer after use.
Storage
Metered-dose inhaler: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Exposure to temperatures >48°C (120°F) may cause bursting. Do not puncture inhaler, throw into a fire or incinerator, or use or store near heat or open flame.
Nebulization solution: Store at 15°C to 30°C (59°F to 86°F). Protect from light. Store unused vials in foil pouch.
Drug Interactions
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy
Anticholinergic Agents: Ipratropium (Oral Inhalation) may enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy
Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Exceptions: Cannabidiol. Monitor therapy
Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Monitor therapy
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination
Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination
Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Avoid combination
Methacholine: Ipratropium (Oral Inhalation) may diminish the therapeutic effect of Methacholine. Management: Hold ipratropium for 12 hours before methacholine use. Consider therapy modification
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy
Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Monitor therapy
Opioid Agonists: Anticholinergic Agents may enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination
Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Avoid combination
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy
Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Avoid combination
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Consider therapy modification
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Adverse Reactions
>10%: Respiratory: Bronchitis (10% to 23%), exacerbation of chronic obstructive pulmonary disease (8% to 23%), sinusitis (1% to 11%)
1% to 10%:
Central nervous system: Headache (6% to 7%), dizziness (3%)
Gastrointestinal: Dyspepsia (1% to 5%), nausea (4%), xerostomia (2% to 4%), dysgeusia (1%)
Genitourinary: Urinary tract infection (2% to 10%)
Neuromuscular & skeletal: Back pain (2% to 7%)
Respiratory: Dyspnea (7% to 8%), flu-like symptoms (4% to 8%), cough (>3%), rhinitis (>3%), upper respiratory tract infection (>3%)
<1%, postmarketing, and/or case reports: Accommodation disturbance, acute eye pain, anaphylaxis, angioedema, blurred vision, bronchospasm, conjunctival hyperemia, constipation, corneal edema, decreased gastrointestinal motility, diarrhea, dry throat, glaucoma, hypersensitivity reaction, hypotension, increased intraocular pressure, laryngospasm, mouth edema, mydriasis, nausea, palpitations, pharyngeal edema, pruritus, skin rash, stomatitis, tachycardia, throat irritation, urinary retention, urticaria, visual halos around lights, vomiting
Warnings/Precautions
Concerns related to adverse effects:
- Bronchospasm: Paradoxical bronchospasm that may be life-threatening and may occur with use of inhaled bronchodilating agents; this should be distinguished from inadequate response. If paradoxical bronchospasm occurs, discontinue ipratropium and institute alternative therapy.
- CNS effects: May cause dizziness and blurred vision; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
- Hypersensitivity reactions: Hypersensitivity reactions (urticaria, angioedema, rash, bronchospasm, oropharyngeal edema), including anaphylaxis, have been reported. Discontinue therapy immediately if patient develops an allergic reaction.
Disease-related concerns:
- Glaucoma: Use with caution in patients with narrow-angle glaucoma; may increase intraocular pressure.
- Prostatic hyperplasia/bladder neck obstruction: Use with caution in patients with prostatic hyperplasia or bladder neck obstruction; may cause urinary retention.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions for more detailed information.
Other warnings/precautions:
- Appropriate use: Not indicated for the initial treatment of acute episodes of bronchospasm where rescue therapy is required for rapid response. Only use in acute exacerbations of asthma in conjunction with short-acting beta-adrenergic agonists for acute episodes (NAEPP 2007).
Monitoring Parameters
FEV1, peak flow, and/or other pulmonary function tests; signs/symptoms of glaucoma; hypersensitivity reactions; urinary retention
Pregnancy
Pregnancy Considerations
Systemic exposure following inhalation is negligible; maternal use is not expected to result in fetal exposure. Based on available information, an increased risk of adverse maternal or fetal outcomes has not been observed following use during pregnancy.
Patient Education
What is this drug used for?
- It is used to open the airways in lung diseases where spasm may cause breathing problems.
- This drug is not to be used to treat intense flare-ups of shortness of breath. Use a rescue inhaler. Talk with the doctor.
Frequently reported side effects of this drug
- Back pain
- Headache
- Dry mouth
- Flu-like symptoms
- Nasal irritation
- Sore throat
- Stuffy nose
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain.
- Vision changes
- Eye pain
- Severe eye irritation
- Seeing halos or bright colors around lights
- Red eyes
- Difficulty urinating
- Unable to pass urine
- Passing a lot of urine
- Severe dizziness
- Passing out
- Fast heartbeat
- Abnormal heartbeat
- Mouth sores
- Mouth irritation
- Difficulty breathing
- Wheezing
- Cough
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
