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Ipratropium and Albuterol

Pronunciation

Pronunciation

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

Index Terms

  • Albuterol and Ipratropium
  • Albuterol/Ipratropium
  • 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:

DuoNeb: Ipratropium bromide 0.5 mg and albuterol (base) 2.5 mg per 3 mL (30s [DSC], 60s [DSC])

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
  • DuoNeb [DSC]

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)

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

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

Dosing: Adult

COPD: Oral inhalation:

Metered dose inhaler (MDI): One inhalation 4 times daily (maximum: 6 inhalations/24 hours).

Nebulization solution: Initial: 1 vial (3 mL) (ipratropium bromide 0.5 mg/albuterol 2.5 mg) every 6 hours (maximum: 1 vial every 4 hours)

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

MDI: 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 MDI) 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:

MDI: 2 to 3 inhalations every 6 hours (NAEPP 2007). Note: Dosing is based on the discontinued CFC-propelled Combivent formulation. Combivent Respimat (non-CFC MDI) 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: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution.

Administration

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

MDI: 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.

Storage

Solution, for nebulization:

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.

Solution, for oral inhalation: Store at 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, whichever comes first.

Drug Interactions

AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy

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

Analgesics (Opioid): Anticholinergic Agents may enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. 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

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: 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. Avoid combination

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. 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

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

MAO Inhibitors: May enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. 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

OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. 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

RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy

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

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

Percentages reported with combination product (not versus placebo). Also see individual agents.

>10%: Respiratory: Bronchitis (2% to 12%), upper respiratory tract infection (3% to 11%)

1% to 10%:

Cardiovascular: Chest pain (≤3%), angina (<2%), arrhythmia (<2%), edema (<2%), hypertension (<2%), palpitation (<2%), tachycardia (<2%)

Central nervous system: Headache (3% to 6%), pain (1% to 3%), dizziness (<2%), fatigue (<2%), insomnia (<2%), nervousness (<2%)

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

Endocrine & metabolic: Hypokalemia (<2%)

Gastrointestinal: Diarrhea (≤2%), dyspepsia (≤2%), nausea (1% to 2%), constipation (<2%), dry throat (<2%), sputum increased (<2%), taste perversion (<2%), vomiting (<2%), xerostomia (<2%)

Genitourinary: Urinary tract infection (≤2%), dysuria (<2%)

Neuromuscular & skeletal: Arthralgia (<2%), muscle spasms (<2%), myalgia (<2%), paresthesia (<2%), tremor (<2%), weakness (<2%), leg cramps (1%)

Ocular: Eye pain (<2%)

Respiratory: Lung disease (6%), dyspnea (2% to 5%), cough (3% to 7%), pharyngitis (2% to 4%), bronchospasm (<2%), pharyngolaryngeal pain (<2%), wheezing (<2%), respiratory disorder (3%), sinusitis (2%), pneumonia (1%), rhinitis (1%)

Miscellaneous: Dysphonia (<2%), flu-like syndrome (1%)

<1% (Limited to important or life-threatening): Allergic reactions (angioedema of tongue, lips or face; laryngospasm, pruritus, rash, urticaria); alopecia, anaphylactic reaction, angioedema, blurred vision, CNS stimulation, conjunctival hyperemia, COPD exacerbation, corneal edema, gastrointestinal motility disorder, glaucoma, halo vision, hyperhidrosis, hypersensitivity reactions, hypotension, intraocular pressure increased, mental disorder, metabolic acidosis, mucosal ulcers, myocardial ischemia, mydriasis, narrow-angle glaucoma precipitation, stomatitis

Warnings/Precautions

Concerns related to adverse effects:

• Bronchospasm: Rarely, paradoxical bronchospasm may occur with use of inhaled bronchodilating agents; this should be distinguished from inadequate response.

• Hypersensitivity reactions: Immediate hypersensitivity reactions (urticaria, angioedema, rash, bronchospasm) have been reported.

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

Disease-related concerns:

• Asthma: Appropriate use: Ipratropium is not indicated for the initial treatment of acute episodes of bronchospasm.

• Cardiovascular disease: Use albuterol with caution in patients with cardiovascular disease (arrhythmia or hypertension or HF); beta-agonists may 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.

• Glaucoma: Use ipratropium with caution in patients with narrow-angle glaucoma; ipratropium 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.

• Pheochromocytoma: Use albuterol with caution in patients with pheochromocytoma; sympathomimetic effects may be increased.

• 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.

Special populations:

• Elderly: Ipratropium has not been specifically studied in elderly patients, but it is poorly absorbed from the airways and appears to be safe in this population. Because of its minimal effect on beta1-receptors and its relatively long duration of action, albuterol is a rational choice in elderly patients when a beta-agonist is indicated; oral albuterol use should be avoided in elderly patients due to adverse effects.

• Pediatric: Some adverse reactions may occur more frequently in children 2 to 5 years of age than in adults and older children. Safety and efficacy have not been established in children.

Other warnings/precautions:

• Appropriate use: Do not exceed recommended dose; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics.

• Tolerance: Excessive use may result in tolerance.

Monitoring Parameters

Spirometry (FEV, FVC); shortness of breath; peak flow and/or other pulmonary function tests; serum potassium

Pregnancy Risk Factor

C

Pregnancy Considerations

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

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience tremors. Have patient report immediately to prescriber signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), angina, tachycardia, abnormal heartbeat, uncontrolled breathing attack, decreased peak flow measurement, severe anxiety, severe dizziness, passing out, severe headache, vision changes, eye pain, severe eye irritation, visual halos or bright colors around lights, difficult urination, difficulty breathing, wheezing, or cough (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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