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Ipratropium and Albuterol

Medically reviewed by Drugs.com. Last updated on Feb 8, 2020.

Pronunciation

(i pra TROE pee um & al BYOO ter ole)

Index Terms

  • Albuterol and Ipratropium
  • Albuterol/Ipratropium
  • Duoneb
  • Ipratropium/Albuterol Sulfate
  • Salbutamol and Ipratropium

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, for nebulization:

Generic: Ipratropium bromide 0.5 mg and albuterol (base) 2.5 mg per 3 mL (30s, 60s)

Solution, for oral inhalation [spray]:

Combivent Respimat: Ipratropium bromide 20 mcg and albuterol (base) 100 mcg per inhalation (4 g) [contains benzalkonium chloride]

Brand Names: U.S.

  • Combivent Respimat

Pharmacologic Category

  • Anticholinergic Agent
  • Beta2-Adrenergic Agonist

Pharmacology

See individual agents.

Use: Labeled Indications

Chronic obstructive pulmonary disease: Treatment of chronic obstructive pulmonary disease (COPD) in those patients who are currently on a regular bronchodilator who continue to have bronchospasms and require a second bronchodilator

Off Label Uses

Acute asthma (exacerbations)

Controlled trials and a meta-analysis have demonstrated that the addition of ipratropium to short-acting beta-agonist (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 [Griffiths 2013], [Rodrigo 2000].

Based on the National Heart, Lung, and Blood Institute/National Asthma Education and Prevention Program guidelines, the use of ipratropium in combination with albuterol is an effective and recommended treatment in the management of patients with asthma exacerbation [NAEPP 2007].

Contraindications

Hypersensitivity to ipratropium, albuterol, atropine (and its derivatives) or any component of the formulation

Documentation of allergenic cross-reactivity for anticholinergics or sympathomimetics is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Canadian labeling: Additional contraindications (not in US labeling): Cardiac tachyarrhythmias, hypertrophic obstructive cardiomyopathy

Dosing: Adult

Note: In patients with coronavirus disease 2019 (COVID-19) who require bronchodilator therapy for asthma or COPD symptoms, the use of pressurized metered-dose inhalers as opposed to nebulized delivery is preferred. Nebulized delivery may increase the transmission of particles (SARS-CoV2) into the environment and potentially decrease the expiratory circuit filter life (AARC 2020).

COPD: Oral inhalation:

Soft-mist inhaler: One inhalation 4 times daily (maximum: 6 inhalations/day)

Nebulization solution: Initial: 1 vial (3 mL) (ipratropium bromide 0.5 mg/albuterol 2.5 mg) every 6 hours (maximum: 6 vials [18 mL]/day)

Acute asthma (exacerbations) (off-label use): Oral inhalation:

Soft-mist inhaler: 8 inhalations every 20 minutes as needed for up to 3 hours (NAEPP 2007). Note: Dosing is based on the discontinued CFC-propelled Combivent formulation. Combivent Respimat (non-CFC soft-mist inhaler) has not been evaluated for use in patients with asthma exacerbation although dosing of Combivent Respimat for FDA approved indications is 50% of CFC-propelled Combivent dosing.

Nebulization solution: 1 vial (3 mL) every 20 minutes for 3 doses, then as needed (NAEPP 2007)

Bronchospasm, asthma (quick relief) (off-label use): Oral inhalation:

Soft-mist inhaler: 2 to 3 inhalations every 6 hours (NAEPP 2007). Note: Dosing is based on the discontinued CFC-propelled Combivent formulation. Combivent Respimat (non-CFC soft-mist inhaler) has not been evaluated for use in patients with asthma exacerbation although dosing of Combivent Respimat for FDA approved indications is 50% of CFC-propelled Combivent dosing.

Nebulization solution: 1 vial (3 mL) every 4 to 6 hours (NAEPP 2007)

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: In patients with coronavirus disease 2019 (COVID-19) who require bronchodilator therapy for asthma symptoms, the use of pressurized metered-dose inhalers as opposed to nebulized delivery is preferred. Nebulized delivery may increase the transmission of particles (SARS-CoV2) into the environment and potentially decrease the expiratory circuit filter life (AARC 2020).

Asthma, acute exacerbation: Limited data available: Note: Only indicated for severe exacerbations 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 (NAEPP 2007):

Infants and Children: Nebulization solution (ipratropium bromide 0.5 mg/albuterol 2.5 mg): Oral inhalation: 1.5 to 3 mL every 20 minutes for 3 doses, then as needed for up to 3 hours.

Adolescents: Nebulization solution (ipratropium bromide 0.5 mg/albuterol 2.5 mg): Oral inhalation: 3 mL every 20 minutes for 3 doses, then as needed for up to 3 hours.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Administration

For oral inhalation; avoid spraying in eyes.

Nebulization solution: Administer via jet nebulizer to an air compressor with an adequate air flow, equipped with a mouthpiece or face mask.

Soft-mist inhaler: Prior to first use (or if not used in >21 days), point towards ground and actuate until aerosol cloud is seen, then repeat 3 additional times before use. If not used for >3 days; actuate once before use. Clean the mouthpiece (including the metal part inside the mouthpiece) at least once a week with a damp cloth or tissue only.

Storage

Nebulization solution:

US labeling: Store at 2°C to 25°C (36°F to 77°F). Protect from light.

Canadian labeling: Store at 15°C to 25°C (59°F to 77°F). Protect from light and heat.

Soft mist inhaler: Store at 20°C to 25°C (68°F to 77°F). Excursions permitted to 15°C to 30°C (59°F to 86°F); avoid freezing. Discard 3 months after first actuation or after labeled number of actuations has been reached and locking mechanism is engaged, whichever comes first.

Drug Interactions

Acetylcholinesterase Inhibitors: Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase Inhibitors may diminish the therapeutic effect of Anticholinergic Agents. 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

AtoMOXetine: May enhance the tachycardic effect of Beta2-Agonists. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Atosiban: Beta2-Agonists may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy

Beta-Blockers (Beta1 Selective): May diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Monitor therapy

Beta-Blockers (Nonselective): May diminish the bronchodilatory effect of Beta2-Agonists. Avoid combination

Betahistine: May diminish the therapeutic effect of Beta2-Agonists. Monitor therapy

Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. 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

Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Consider therapy modification

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

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

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Monitor therapy

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification

Loop Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

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

Monoamine Oxidase Inhibitors: May enhance the adverse/toxic effect of Beta2-Agonists. 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

Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Management: Concomitant use of ozanimod with sympathomimetic agents is not recommended. If combined, monitor patients closely for the development of hypertension, including hypertensive crises. Consider therapy modification

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. Avoid combination

Procarbazine: May enhance the adverse/toxic effect of Sympathomimetics. Management: Consider alternatives to this combination when possible. Procarbazine prescribing information states that this combination should be avoided. Consider therapy modification

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

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

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Thiazide and Thiazide-Like Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

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

Also see individual agents.

1% to 10%:

Cardiovascular: Angina pectoris (<2%), cardiac arrhythmia (<2%), chest discomfort (<2%), edema (<2%), hypertension (<2%), palpitations (<2%), tachycardia (<2%)

Central nervous system: Headache (3%), pain (≥2%), dizziness (<2%), fatigue (<2%), insomnia (<2%), nervousness (<2%), voice disorder (<2%)

Dermatologic: Pruritus (<2%), skin rash (<2%)

Endocrine & metabolic: Hypokalemia (<2%)

Gastrointestinal: Constipation (<2%), diarrhea (<2%), dysgeusia (<2%), dyspepsia (<2%), vomiting (<2%), xerostomia (<2%)

Genitourinary: Dysuria (<2%), urinary tract infection (<2%)

Neuromuscular & skeletal: Arthralgia (<2%), asthenia (<2%), muscle spasm (<2%), myalgia (<2%), tremor (<2%)

Ophthalmic: Eye pain (<2%)

Respiratory: Cough (3% to 7%), nasopharyngitis (4%), bronchitis (3%), upper respiratory tract infection (3%), pharyngitis (≥2%), respiratory insufficiency (≥2%), sinusitis (≥2%), dyspnea (2%), bronchospasm (<2%), dry throat (<2%), flu-like symptoms (<2%), increased bronchial secretions (<2%), pharyngolaryngeal pain (<2%), wheezing (<2%)

Frequency not defined: Gastrointestinal: Nausea

<1%, postmarketing, and/or case reports: Accommodation disturbance, anaphylaxis, angioedema, blurred vision, central nervous system stimulation, conjunctival hyperemia, corneal edema, decreased diastolic blood pressure, dry secretions, eye irritation, gastrointestinal motility disorder, glaucoma, hyperhidrosis, hypersensitivity reaction, increased systolic blood pressure, ischemic heart disease, mouth edema, myasthenia, mydriasis, nasal congestion, paradoxical bronchospasm, pharyngeal edema, psychiatric disturbance, stomatitis, throat irritation, urinary retention, visual halos around lights

Warnings/Precautions

Concerns related to adverse effects:

• Bronchospasm: Paradoxical bronchospasm that may be life-threatening may occur with use of inhaled bronchodilating agents; this should be distinguished from inadequate response. If bronchospasm occurs, discontinue ipratropium/albuterol 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.

• Serious effects/fatalities: Do not exceed recommended dose or frequency or use with other medications containing LABAs; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics.

• Sympathomimetic amines sensitivity: Use albuterol with caution in patients with sensitivity to sympathomimetic amines.

Disease-related concerns:

• Cardiovascular disease: Use albuterol with caution in patients with cardiovascular disease (arrhythmia, coronary insufficiency, hypertension, HF); beta-agonists have been reported to produce ECG changes (flattening of the T wave, prolongation of the QTc interval, ST segment depression) and/or cause elevation in blood pressure, heart rate and result in CNS stimulation/excitation. Beta2-agonists may also increase risk of arrhythmias and myocardial ischemia. In a scientific statement from the American Heart Association, albuterol has been determined to be an agent that may either cause direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: moderate to major) (AHA [Page 2016]).

• Diabetes: Use albuterol with caution in patients with diabetes mellitus; beta2-agonists may increase serum glucose (effect is usually transient).

• Glaucoma: Use ipratropium with caution in patients with narrow-angle glaucoma; may increase intraocular pressure.

• Hyperthyroidism: Use albuterol with caution in hyperthyroidism; may stimulate thyroid activity.

• Hypokalemia: Use albuterol with caution in patients with hypokalemia; beta2-agonists may decrease serum potassium (effect is usually transient).

• Prostatic hyperplasia/bladder neck obstruction: Use ipratropium with caution in patients with prostatic hyperplasia or bladder neck obstruction; ipratropium may cause urinary retention.

• Seizure disorder: Use albuterol with caution in patients with seizure disorders; beta-agonists may result in CNS stimulation/excitation.

Monitoring Parameters

FEV1, peak flow, and/or other pulmonary function tests; blood pressure, heart rate; CNS stimulation; serum glucose, serum potassium; signs/symptoms of glaucoma; hypersensitivity reactions; urinary retention; shortness of breath

Pregnancy Considerations

Refer to individual monographs.

Patient Education

What is this drug used for?

• It is used to open the airways in lung diseases where spasm may cause breathing problems.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Tremors

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat.

• Chest pain

• Fast heartbeat

• Abnormal heartbeat

• Uncontrolled breathing attack

• Decreased peak flow measurement

• Severe anxiety

• Severe dizziness

• Passing out

• Severe headache

• Vision changes

• Eye pain

• Severe eye irritation

• Seeing halos or bright colors around lights

• Difficult urination

• Trouble breathing

• Wheezing

• Cough

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, 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 limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.