Version May 2024
Asthma, acute exacerbation, moderate to severe (off-label use): Note: May consider for treatment of moderate to severe exacerbations (eg, critically ill) in combination with a short-acting beta-adrenergic agonist. Nebulized therapy may be preferred in patients who have more severe symptoms or who cannot effectively use an inhaler (Ref).
Nebulization solution: Oral inhalation: 0.5 mg every 20 minutes for 3 doses, then hourly as needed for up to 3 hours (Ref).
Metered-dose inhaler (17 mcg/actuation): Oral inhalation: 4 to 8 inhalations with spacer every 20 minutes for 3 doses, then hourly as needed for up to 3 hours (Ref).
Chronic obstructive pulmonary disease:
Acute exacerbation: Note: Although similar efficacy exists among formulations, some experts prefer nebulized therapy during severe chronic obstructive pulmonary disease (COPD) exacerbations (Ref). May be used in combination with an inhaled short-acting beta agonist (Ref).
For patients at home or office management:
Metered-dose inhaler (17 mcg/actuation): Oral inhalation: 2 inhalations every 4 to 6 hours as needed (Ref).
Nebulization solution: Oral inhalation: 0.5 mg every 6 to 8 hours as needed (Ref).
For patients requiring emergency department or hospital-based care:
Nebulization solution: Oral inhalation: 0.5 mg every 1 hour (up to 3 doses), then every 2 to 4 hours as needed (Ref).
Metered-dose inhaler (17 mcg/actuation): Oral inhalation: 2 to 4 inhalations every 1 hour (up to 3 doses), then every 2 to 4 hours as needed (Ref).
Intermittent symptom relief: Note: Use for intermittent symptoms on an as-needed basis rather than regularly scheduled maintenance therapy. Typically used in combination with inhaled short-acting beta agonist (SABA); combination therapy provides greater improvement in FEV1 and symptoms over monotherapy SABA (Ref).
Metered-dose inhaler (17 mcg/actuation): Oral inhalation: 2 inhalations 4 to 6 times daily as needed (Ref).
Nebulization solution: Oral inhalation: 0.5 mg every 4 to 8 hours as needed (Ref).
Maintenance (alternative agent): Note: Depending on symptoms and exacerbation risk, preferred therapy is a single long-acting bronchodilator (long-acting beta agonist or long-acting muscarinic antagonist). In patients with more symptoms (eg, Group B), preferred therapy is dual long-acting bronchodilator therapy (Ref).
Metered-dose inhaler (17 mcg/actuation): Oral inhalation: 2 inhalations every 6 hours.
Nebulization solution: Oral inhalation: 0.5 mg every 6 to 8 hours.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
(For additional information see "Ipratropium (oral inhalation): Pediatric drug information")
Asthma, acute exacerbation: Limited data available (Ref): 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 (Ref):
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 (Ref)
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 therapy (nonacute): Limited data available: Note: Evidence is lacking that ipratropium provides added benefit to beta-2 agonists in long-term control asthma therapy (Ref)
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 (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (not studied); however, dosage adjustment unlikely necessary due to low systemic absorption.
There are no dosage adjustments provided in the manufacturer's labeling (not studied); however, dosage adjustment unlikely necessary due to low systemic absorption.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>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
Hypersensitivity to ipratropium, atropine (and its derivatives), or any component of the formulation
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.
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).
Atrovent HFA 12.9 g canister contains 200 inhalations.
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)
Solution, Inhalation, as bromide:
Generic: 0.02% (2.5 mL)
Solution, Inhalation, as bromide [preservative free]:
Generic: 0.02% (2.5 mL)
May be product dependent
Aerosol solution (Atrovent HFA Inhalation)
17 mcg/ACT (per gram): $43.91
Solution (Ipratropium Bromide Inhalation)
0.02% (per mL): $0.14 - $0.89
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Aerosol Solution, Inhalation:
Atrovent HFA: 20 mcg/actuation (1 ea) [contains alcohol, usp]
Nebulization Solution, Inhalation:
Generic: 0.125 mg/mL (2 mL); 0.25 mg/mL (0.5 mL, 1 mL, 2 mL, 20 mL)
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. Compatibility with other medications (eg, albuterol, budesonide) in nebulizer has been reported (Ref); also refer to institution-specific policies.
Inhalation:
Nebulization: May be administered with or without dilution in NS; use of a nebulizer with a mouth piece, rather than a face mask, may be preferred to prevent contact with eyes. Compatibility with other medications (eg, albuterol, budesonide) in nebulizer has been reported (Ref); also refer to institution-specific policies.
Oral Inhalation (metered-dose inhaler): Atrovent HFA: Prior to initial use, prime inhaler by releasing 2 test sprays into the air. If the inhaler has not been used for >3 days, reprime. Avoid spraying into the eyes. Use spacer device in children <8 years; use spacer device and face mask for children ≤4 years.
Chronic obstructive pulmonary disease: Maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema
Asthma, acute exacerbation, moderate to severe
Atrovent may be confused with Alupent, Serevent
Ipratropium may be confused with tiotropium
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Anticholinergic Agents: Ipratropium (Oral Inhalation) may enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination
Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: 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. Risk X: Avoid combination
Methacholine: Ipratropium (Oral Inhalation) may diminish the therapeutic effect of Methacholine. Management: Hold ipratropium for 12 hours before methacholine use. Risk D: Consider therapy modification
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: 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. Risk C: 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. Risk C: Monitor therapy
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: 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. Risk X: Avoid combination
Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid combination
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk X: Avoid combination
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination
Rivastigmine: Anticholinergic Agents may diminish the therapeutic effect of Rivastigmine. Rivastigmine may diminish the therapeutic effect of Anticholinergic Agents. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Systemic exposure following inhalation is negligible; maternal use is not expected to result in fetal exposure. Data related to ipratropium for the treatment of asthma in pregnancy are limited. Based on available information, an increased risk of adverse maternal or fetal outcomes has not been observed following use during pregnancy.
Uncontrolled asthma is associated with adverse events on pregnancy (increased risk of perinatal mortality, preeclampsia, preterm birth, low birth weight infants, cesarean delivery, and the development of gestational diabetes). Poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used asthma medications. Maternal treatment improves pregnancy outcomes by reducing the risk of some adverse events (eg, preterm birth, gestational diabetes). Maternal asthma symptoms should be monitored monthly during pregnancy (ERS/TSANZ [Middleton 2020]; GINA 2023).
It is not known if ipratropium is present in breast milk.
Systemic exposure following inhalation is negligible which would limit excretion into breast milk. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
FEV1, peak flow, and/or other pulmonary function tests; signs/symptoms of glaucoma; hypersensitivity reactions; urinary retention
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.
Onset of action: Bronchodilation: Within 15 minutes
Peak effect: 1 to 2 hours
Duration: Metered-dose inhaler: 2 to 4 hours; Nebulization solution: 4 to 5 hours, up to 7 to 8 hours in some patients
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 lower airways
Protein Binding: ≤9%
Metabolism: Partially metabolized to inactive ester hydrolysis products
Half-life elimination: 2 hours
Excretion: Urine (50%)
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