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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
Hypersensitivity to ipratropium, albuterol, atropine (and its derivatives) or any component of the formulation
Combivent aerosol inhaler [DSC]: Additional contraindication: Hypersensitivity to soya lecithin or related food products (eg, soybean and peanut)
Canadian labeling: Additional contraindications (not in US labeling): Cardiac tachyarrhythmias, hypertrophic obstructive cardiomyopathy
COPD: Oral inhalation:
Aerosol for inhalation:
Combivent [DSC]: Two inhalations 4 times daily (maximum: 12 inhalations/24 hours)
Combivent Respimat: One inhalation 4 times daily (maximum: 6 inhalations/24 hours)
Solution for nebulization: Initial: 1 vial (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:
Nebulization: 1 vial (3 mL) every 20 minutes for 3 doses, then as needed (NAEPP 2007)
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.
Refer to adult dosing.
There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied); use with caution.
There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied); use with caution.
Nebulization: Administer via jet nebulizer to an air compressor with an adequate air flow, equipped with a mouthpiece or face mask.
Metered-dose inhaler (MDI):
Combivent [DSC]: Shake canister vigorously for ≥10 seconds. Prior to first use (or if not used for >24 hours), a test spray of 3 sprays is recommended.
Combivent Respimat: 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.
The Combivent aerosol dosage form [DSC] contains soya lecithin. Do not use in patients allergic to soya lecithin or related food products such as soybean and peanut.
Aerosol, for oral inhalation: Combivent [DSC]: Store at 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). Avoid excessive humidity. Do not store near heat or open flame. Discard after labeled number of actuations has been reached.
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Aerosol, for oral inhalation:
Combivent: Ipratropium bromide 18 mcg and albuterol (base) 90 mcg per inhalation (14.7 g [DSC]) [contains chlorofluorocarbon, soya lecithin]
Solution, for nebulization: Ipratropium bromide 0.5 mg and albuterol (base) 2.5 mg per 3 mL (30s, 60s)
DuoNeb: Ipratropium bromide 0.5 mg and albuterol (base) 2.5 mg per 3 mL (30s [DSC], 60s [DSC])
Solution, for oral inhalation [spray]:
Combivent Respimat: Ipratropium bromide 20 mcg and albuterol (base) 100 mcg per inhalation (4 g) [contains benzalkonium chloride]
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
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination
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
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
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 using drugs with substantial anticholinergic effects in patients receiving secretin whenever possible. If such agents must be used in combination, monitor closely for a diminished response to 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
Spirometry (FEV, FVC); weight
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
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. The Canadian labeling contraindicates use in patients with tachyarrhythmias or hypertrophic obstructive cardiomyopathy.
- 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.
Dosage form specific issues:
- Soya lecithin: Combivent aerosol inhaler [DSC]: Contains soya lecithin; use is contraindicated in patients with allergy to soya lecithin or related food products (eg, soybean, peanut)
Other warnings/precautions:
- Appropriate use: Do not exceed recommended dose; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics.
- Patient education: A spacer device is recommended when using a metered-dose inhaler.
- Tolerance: Excessive use may result in tolerance.
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Animal reproduction studies have not been conducted with this combination. See individual agents.
See individual agents.
- 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, uncontrolled breathing attack, decreased peak flow measurement, severe anxiety, severe dizziness, passing out, severe headache, 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 healthcare 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.