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Ipratropium and Albuterol

Generic name: albuterol/ipratropium systemic

Brand names: Combivent, DuoNeb, Combivent Respimat

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]

Pharmacology

Mechanism of Action

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

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 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 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. .

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

Dosage and Administration

Dosing: Adult

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)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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.

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 25°C (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: 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

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

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

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. 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.

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 database for more detailed information.

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

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted with this combination. See individual agents.

Patient Education

What is this drug used for?

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

Frequently reported side effects of this drug

  • Tremors

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

  • 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
  • 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.

Source: Wolters Kluwer Health. Last updated January 15, 2020.