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    Respiratory Short-Acting Beta-2 Agonists in Combination with Respiratory Short-Acting Muscarinic Antagonists

    DEA CLASS

    Rx

    DESCRIPTION

    Combination of a short-acting antimuscarinic agent (ipratropium), with a short-acting beta-agonist (SABA, albuterol)
    Primarily used in the treatment of COPD in adults, also used off-label for acute asthma exacerbation in adult and pediatric patients
    Available as an oral inhalation or nebulizer solution

    COMMON BRAND NAMES

    Combivent Respimat, DuoNeb

    HOW SUPPLIED

    Combivent Respimat Respiratory (Inhalation) Spray Met: 1actuation, 20-100mcg
    DuoNeb/Ipratropium Bromide, Albuterol Sulfate/Ipratropium, Albuterol Respiratory (Inhalation) Sol: 3mL, 0.5-3mg

    DOSAGE & INDICATIONS

    For the treatment of chronic obstructive pulmonary disease (COPD) (e.g., chronic bronchitis or emphysema).
    Oral Inhalation dosage (inhalation aerosol; i.e., Combivent Respimat)
    Adults

    1 actuation via oral inhalation 4 times per day. Each actuation delivers 20 mcg of ipratropium bromide (monohydrate) and 100 mcg of albuterol (equivalent to 120 mcg of albuterol sulfate). Patients may take additional inhalations as required. Max: 6 inhalations per 24 hours. The combination is indicated for COPD patients who are receiving a regular aerosol bronchodilator and who continue to have evidence of bronchospasm which requires a second bronchodilator. The optimal dosage for acute COPD exacerbation is not established; titrate to clinical symptoms and adverse effects/tolerance.[55976] Ipratropium; albuterol may be used in Group A patients and may also be used in Groups B, C, and D for additional symptom control. Evidence does not support the use of high doses of albuterol on an "as needed" basis in patients already treated with long-acting bronchodilators. Ipratropium; albuterol may also be used for acute COPD exacerbations.[63765]

    Nebulizer Inhalation dosage (solution for nebulization; e.g., DuoNeb)
    Adults

    1 vial via nebulizer 4 times per day. Each 3-mL vial contains 0.5 mg of ipratropium and 3 mg albuterol sulfate (2.5 mg of albuterol base). Up to 2 additional doses may be allowed per day, if needed. Max: 6 vials per day via nebulizer. Additional doses or increased frequency of administration have not been studied. The safety and efficacy of extra doses of ipratropium or albuterol in addition to the doses of the combination product have not been studied.[43675] The optimal dosage for acute COPD exacerbation is not established; titrate to clinical symptoms and adverse effects/tolerance.[55976] According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for COPD, ipratropium; albuterol may be used in Group A patients and may also be used in Groups B, C, and D for additional symptom control. Ipratropium; albuterol may be used for acute COPD exacerbations.[63765] No significant differences in FEV1 have been demonstrated between metered-dose inhalers (with or without a spacer) and nebulizers among short-acting bronchodilators in clinical trials; nebulizers may be more convenient for more acutely ill patients.[63765]

    For the treatment of asthma exacerbation†.
    Respiratory (Inhalation) dosage (inhalation solution; e.g., DuoNeb)
    Adults

    0.5 mg ipratropium bromide/2.5 mg albuterol (3 mL) inhaled by nebulizer every 20 minutes for 3 doses, then as needed, usually every 4 to 6 hours. Ipratropium may provide additive benefit to a short-acting beta-agonist (SABA) during early treatment of severe asthma exacerbation in the emergency department or during medical transport, such as fewer hospitalizations and greater improvement in FEV1 compared to SABA alone. There is a lack of data to support the use of ipratropium in addition to an SABA once a patient is hospitalized or as part of a chronic asthma regimen.

    Adolescents

    0.5 mg ipratropium bromide/2.5 mg albuterol (3 mL) inhaled by nebulizer every 20 minutes for 3 doses, then as needed, usually every 4 to 6 hours in the emergency care setting. Data supporting continued use of ipratropium in addition to a short-acting beta-agonist (SABA) once a patient is hospitalized are lacking.

    Children 6 to 12 years

    0.25 mg ipratropium bromide/1.25 mg albuterol (1.5 mL) or 0.5 mg ipratropium bromide/2.5 mg albuterol (3 mL) inhaled by nebulizer every 20 minutes for 3 doses, then as needed, usually every 4 to 6 hours in the emergency care setting. Data supporting continued use of ipratropium in addition to a short-acting beta-agonist (SABA) once a patient is hospitalized are lacking.

    Infants and Children 1 to 5 years

    0.25 mg ipratropium bromide/1.25 mg albuterol (1.5 mL) inhaled by nebulizer every 20 minutes for 3 doses has been recommended for moderate to severe asthma exacerbation in the emergency care setting in patients with poor response to initial short-acting beta-agonist (SABA). Data suggest that ongoing use of ipratropium in addition to SABA after 1 hour is unlikely to confer additional benefit vs. as-needed use of the SABA alone in this population.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    6 inhalations/day for Combivent Respimat inhalation spray; one 3-mL vial of DuoNeb administered 6 times/day via nebulization.

    Geriatric

    6 inhalations/day for Combivent Respimat inhalation spray; one 3-mL vial of DuoNeb administered 6 times/day via nebulization.

    Adolescents

    Safe and effective use of Combivent Respimat inhalation spray not established; one 3-mL vial per dose of nebulizer solution (e.g., DuoNeb) nebulization has been used off-label.

    Children

    Safe and effective use of Combivent Respimat inhalation spray not established; 1.5-mL vial per dose of nebulizer solution (e.g., DuoNeb) nebulization has been used off-label.

    Infants

    Safe and effective use of combination product not established.

    Neonates

    Safe and effective use of combination product not established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    For storage information, see the specific product information within the How Supplied section

    Inhalation Administration

    •For inhalational use only.

    Oral Inhalation Administration

    Solution for nebulization (Duoneb):
    No need for dilution prior to use.
    Deliver solution by jet nebulization connected to an air compressor, equipped with a mouthpiece or suitable face mask over a time period of up to 15 minutes.
    The choice of using a mouthpiece versus a face mask must be made based on the skills and understanding of each individual patient.
    Using the 'blow by' technique (i.e., holding the face mask or open tube near the patient's nose and mouth) is not recommended.
    If the patient is using other nebulized medications, instruct them to use ipratropium; albuterol first and wait 10 minutes before using other nebulized medications as directed.
     
    Inhalation spray (Combivent Respimat):
    Instruct patient on proper inhalation technique according to product directions.
    Prior to first use, insert the cartridge into the inhaler and prime the unit by actuating the inhaler toward the ground until an aerosol cloud is visible and then repeating the process three more times. The unit is then considered primed and ready for use. If not used for more than 3 days, patients are to actuate the inhaler once to prepare the inhaler for use. If not used for more than 21 days, patients are to actuate the inhaler until an aerosol cloud is visible and then repeat the process three more times to prepare the inhaler for use.
    To inhale a dose: Hold the inhaler upright with the orange cap closed, so as to not accidentally release a dose of medicine. Turn the clear base in the direction of the white arrows on the label until it clicks (half a turn). Then, flip the orange cap until it snaps fully open. Have patient breathe out slowly and fully, and then close their lips around the end of the mouthpiece without covering the air vents. Point the inhaler to the back of the throat. While the patient takes in a slow, deep breath through the mouth, press the dose release button and continue to have the patient breathe in slowly for as long as they can. The patient should hold the breath for 10 seconds or for as long as comfortable. Close the orange cap until it is time to use the inhaler again.
    The mouthpiece, including the metal part inside the mouthpiece, should be cleaned at least 1 time a week, using only a damp cloth or tissue; any minor discoloration in the mouthpiece does not affect the inhaler. If the outside of the inhaler gets dirty, wipe it with a damp cloth.
    The inhaler contains 60 puffs or 120 puffs, equal to 60 doses or 120 doses. The dose indicator shows approximately how much medicine is left. When the pointer enters the red area of the scale, there is enough medicine for 3 days (60 dose product) or 7 days (120 dose product); once the dose indicator has reached the end of the scale, all 60 or 120 puffs have been used and the inhaler locks automatically. At this point, the base cannot be turned any further.
    The inhaler should be discarded 3 months after insertion of cartridge into inhaler, even if all the medicine has not been used, or when the inhaler is locked (after 60 or 120 puffs), whichever comes first.
    To avoid the spread of infection, do not use the inhaler spray for more than one person.

    STORAGE

    Combivent:
    - Avoid excessive humidity
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Combivent Respimat:
    - Do not freeze
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    DuoNeb:
    - After removing from pouch, protect from light and use product within one week
    - Discard product if solution is not colorless
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in original package until time of use
    - Store unused product in foil pouch

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    The Combivent ipratropium; albuterol aerosol contains flammable ingredients under pressure. To avoid injury, the aerosol should be kept away from extreme heat or flames and the container should not be punctured.
     
    Do not exceed recommended dosages of beta-agonists; fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma. The exact cause of death is unknown, but cardiac arrest after an unexpected development of a severe acute asthmatic crisis and subsequent hypoxia is suspected.

    Albuterol hypersensitivity, levalbuterol hypersensitivity, paradoxical bronchospasm

    Ipratropium; albuterol aerosols can produce a paradoxical bronchospasm that can be life-threatening in some patients. If bronchospasm occurs, the ipratropium; albuterol inhalation should be discontinued immediately and appropriate treatment measures instituted. In rare cases severe allergic reactions, including urticaria, angioedema, rash, oropharyngeal edema, respiratory difficulty, and anaphylaxis have occurred following the use of either ipratropium or albuterol. Ipratropium; albuterol combinations are contraindicated in patients with atropine hypersensitivity, albuterol hypersensitivity, or their respective derivatives (e.g., levalbuterol hypersensitivity and respiratory antimuscarinic hypersensitivity).

    Cardiac arrhythmias, coronary artery disease, hypertension, hypokalemia, QT prolongation

    Albuterol, like other beta2-agonists and sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency (coronary artery disease), cardiac arrhythmias, and hypertension. Ipratropium; albuterol can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, and cardiac arrhythmias, such as supraventricular tachycardia and extrasystoles. If such effects occur, ipratropium; albuterol may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiographic changes, such as flattening of the T wave, QT prolongation, and ST segment depression, although the clinical significance of these findings is unknown. Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Beta-adrenergic agonist therapies like albuterol may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease in serum potassium is usually transient, not requiring supplementation.

    Anticholinergic medications, bladder obstruction, prostatic hypertrophy, urinary retention

    Due to the anticholinergic effects of ipratropium, ipratropium; albuterol combinations should be used with caution in some patient populations. Ipratropium may precipitate urinary retention in patients with preexisting bladder obstruction (of the bladder neck) or prostatic hypertrophy. Although inhaled ipratropium is only minimally absorbed into the systemic circulation, the effects of ipratropium may be additive to other anticholinergic medications.

    Closed-angle glaucoma, contact lenses, ophthalmic administration

    Due to the anticholinergic effects of ipratropium, ipratropium; albuterol combinations should be used with caution in some patient populations. Ipratropium may increase intraocular pressure and aqueous outflow resistance in patients with closed-angle glaucoma, particularly if the medication gets into the eyes. Temporary pain, mydriasis, cycloplegia, blurred vision, conjunctivitis, or visual impairment may result from inadvertent ophthalmic administration. Care should be taken not to spray ipratropium; albuterol in the eyes. The anticholinergic effects of ipratropium may make the eyes dry and this can cause irritation or blurred vision for wearers of contact lenses. The use of lubricating drops may be necessary.

    Diabetes mellitus, hyperthyroidism, pheochromocytoma, seizure disorder, thyrotoxicosis

    Albuterol may exacerbate conditions that are responsive to sympathomimetic stimulation, such as hyperthyroidism (thyrotoxicosis), diabetes mellitus, seizure disorder, pheochromocytoma, or other hypersensitivity to sympathomimetic amines. Caution should be used when ipratropium; albuterol is prescribed to these individuals.

    Labor, obstetric delivery, pregnancy

    There are no randomized clinical studies of ipratropium; albuterol inhalation combinations, or its individual components, ipratropium bromide and albuterol sulfate, during pregnancy. Ipratropium is negligibly absorbed systemically following oral inhalation; therefore, maternal use is not expected to result in fetal exposure to the drug. Published literature, including cohort studies, case control studies and case series, over several decades have not identified a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes with ipratropium bromide. Available data from published epidemiological studies and postmarketing case reports of pregnancy outcomes following inhaled albuterol use do not consistently demonstrate a risk of major birth defects or, miscarriage. There are clinical considerations with the use of ipratropium; albuterol inhalations in pregnant women. During worldwide marketing experience, various congenital anomalies, including cleft palate and limb defects, have been reported in the offspring of patients being treated with albuterol. Some mothers were taking multiple medications during their pregnancies. Because no consistent pattern of defects can be discerned, a relationship between albuterol use and congenital anomalies has not been established. Animal reproduction studies have not been conducted with this inhalation combination; however, animal studies are available with its individual components, ipratropium bromide and albuterol sulfate. Based on oral reproduction studies, no evidence of structural alterations was observed when ipratropium bromide was administered to pregnant mice, rats, and rabbits during organogenesis at doses approximately 340, 68,000 and 17,000 times, respectively, the maximum recommended human daily inhalation dose (MRHDID) in adults on a mg/m2 basis. When oral albuterol was administered to pregnant mice during organogenesis there was evidence of cleft palate at doses approximately equivalent to the MRHDID. Oral albuterol sulfate has been shown to delay preterm labor in some reports. Due to the potential for interference with uterine contractility, the use of ipratropium; albuterol during labor and obstetric delivery should be restricted to those patients in whom the benefits clearly outweigh the risks.

    Breast-feeding

    There are no available data on the presence of ipratropium; albuterol combinations, or its components, ipratropium bromide or albuterol, in human milk, the effects on the breastfed infant, or the effects on milk production. Ipratropium and albuterol concentrations in human breast milk are likely to be low. Caution should be exercised in lactating mothers who may require ipratropium; albuterol combinations. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. According to the 2004 recommendations of the National Asthma Education and Prevention Program (NAEPP) for managing asthma during pregnancy, there is currently no contraindication for use of short-acting inhaled beta-2 agonists during lactation.

    Geriatric

    Clinical studies of ipratropium; albuterol inhalers and nebulizer solutions have included a fair percentage of adults age 65 years and over, and patients 75 years of age and older. No overall differences in safety or effectiveness were observed, and other reported clinical experience has not identified differences in responses. Greater sensitivity of some older individuals cannot be ruled out. Geriatric patients may generally be more sensitive to the side effects of inhaled beta-agonist and anticholinergic therapies and be more likely to experience side effects such as dry mouth or constipation.

    Hepatic disease, renal failure, renal impairment

    The use of ipratropium; albuterol nebulizer solution has not been adequately studied in patients with renal impairment (including renal failure, renal disease) or hepatic disease. There are no precautions listed for hepatic or renal insufficiency with use of ipratropium; albuterol inhalers.

    MAOI therapy

    Ipratropium; albuterol should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors (MAOI therapy), or within 2 weeks of discontinuation of such agents because the action of albuterol on the cardiovascular system may be potentiated.

    Driving or operating machinery

    Since dizziness, accommodation disorder, mydriasis, and blurred vision may occur with use of ipratropium; albuterol, patients should be cautioned about engaging in activities requiring balance and visual acuity such as driving or operating machinery until they are aware of how the inhalation affects them.

    ADVERSE REACTIONS

    Severe

    arrhythmia exacerbation / Early / 0-2.0
    atrial fibrillation / Early / 0.5-0.5
    bronchospasm / Rapid / Incidence not known
    laryngospasm / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    ocular hypertension / Delayed / Incidence not known

    Moderate

    dyspnea / Early / 2.0-4.5
    chest pain (unspecified) / Early / 0.3-2.6
    sinus tachycardia / Rapid / 0-2.0
    edema / Delayed / 0-2.0
    hypertension / Early / 0-2.0
    palpitations / Early / 0-2.0
    angina / Early / 0-2.0
    hypokalemia / Delayed / 0-2.0
    dysuria / Early / 0-2.0
    wheezing / Rapid / 0-2.0
    stomatitis / Delayed / 0-2.0
    constipation / Delayed / 0-2.0
    supraventricular tachycardia (SVT) / Early / 0.5-0.5
    dysphonia / Delayed / 1.0
    QT prolongation / Rapid / Incidence not known
    peripheral vasodilation / Rapid / Incidence not known
    hypotension / Rapid / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    corneal edema / Early / Incidence not known
    urinary retention / Early / Incidence not known
    blurred vision / Early / Incidence not known
    conjunctival hyperemia / Early / Incidence not known
    metabolic acidosis / Delayed / Incidence not known

    Mild

    infection / Delayed / 1.3-10.9
    headache / Early / 2.0-5.6
    pharyngitis / Delayed / 2.2-4.4
    cough / Delayed / 2.0-4.2
    sinusitis / Delayed / 2.3-2.3
    xerostomia / Early / 0-2.0
    dizziness / Early / 0-2.0
    ocular pain / Early / 0-2.0
    anxiety / Delayed / 0-2.0
    tremor / Early / 0-2.0
    insomnia / Early / 0-2.0
    fatigue / Early / 0-2.0
    paresthesias / Delayed / 0-2.0
    dysgeusia / Early / 0-2.0
    diarrhea / Early / 0-2.0
    nausea / Early / 1.4-2.0
    vomiting / Early / 0-2.0
    dyspepsia / Early / 0-2.0
    myalgia / Early / 0-2.0
    asthenia / Delayed / 0-2.0
    arthralgia / Delayed / 0-2.0
    rash / Early / 0.3-1.9
    pruritus / Rapid / 0.3-1.9
    influenza / Delayed / 1.4-1.9
    muscle cramps / Delayed / 1.4-1.4
    rhinitis / Early / 1.1-1.1
    urticaria / Rapid / 0.3-0.3
    ocular irritation / Rapid / Incidence not known
    mydriasis / Early / Incidence not known
    drowsiness / Early / Incidence not known
    hoarseness / Early / Incidence not known
    throat irritation / Early / Incidence not known
    nasal dryness / Early / Incidence not known
    nasal congestion / Early / Incidence not known
    pyrosis (heartburn) / Early / Incidence not known
    flushing / Rapid / Incidence not known
    back pain / Delayed / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    alopecia / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abarelix: (Major) Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of abarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Agents associated with a lower, but possible risk for QT prolongation and torsade de pointes (TdP) based on varying levels of documentation include the beta-agonists. Beta-agonists may cause cardiovascular effects, particularly when used in high doses and/or when associated with hypokalemia.
    Acebutolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Acetaminophen; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Acetaminophen; Caffeine; Pyrilamine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Acetaminophen; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Acetazolamide: (Moderate) Albuterol may cause additive hypokalemia when coadministered with carbonic anhydrase inhibitors. These combinations can lead to symptomatic hypokalemia and associated ECG changes in some susceptible individuals. Monitoring of potassium levels would be advisable.
    Aclidinium: (Moderate) Although aclidinium is minimally absorbed into the systemic circulation after inhalation, there is the potential for aclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics. Per the manufaturer, avoid concomitant administration of aclidinium with other anticholinergic medications, when possible.
    Aclidinium; Formoterol: (Moderate) Although aclidinium is minimally absorbed into the systemic circulation after inhalation, there is the potential for aclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics. Per the manufaturer, avoid concomitant administration of aclidinium with other anticholinergic medications, when possible.
    Acrivastine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Amphetamine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and amphetamine; dextroamphetamine use. Concomitant use may potentiate sympathetic effects.
    Amphetamine; Dextroamphetamine Salts: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and amphetamine; dextroamphetamine use. Concomitant use may potentiate sympathetic effects.
    Amphetamine; Dextroamphetamine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and amphetamine; dextroamphetamine use. Concomitant use may potentiate sympathetic effects.
    Anticholinergics: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Articaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and epinephrine use. Concomitant use may potentiate sympathetic effects.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Aspirin, ASA; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Atenolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Atenolol; Chlorthalidone: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Atropine: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Atropine; Difenoxin: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Atropine; Edrophonium: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Belladonna; Opium: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Bendroflumethiazide; Nadolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Benzphetamine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Benztropine: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Beta-adrenergic blockers: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Betaxolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Bisoprolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Brimonidine; Timolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Brompheniramine; Phenylephrine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Brompheniramine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Budesonide; Glycopyrrolate; Formoterol: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Bumetanide: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
    Bupivacaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and epinephrine use. Concomitant use may potentiate sympathetic effects.
    Butalbital; Acetaminophen; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Caffeine; Sodium Benzoate: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Carbinoxamine; Phenylephrine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Carbinoxamine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Carbonic anhydrase inhibitors: (Moderate) Albuterol may cause additive hypokalemia when coadministered with carbonic anhydrase inhibitors. These combinations can lead to symptomatic hypokalemia and associated ECG changes in some susceptible individuals. Monitoring of potassium levels would be advisable.
    Carteolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Carvedilol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Cetirizine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Chlordiazepoxide; Clidinium: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Chlorpheniramine; Phenylephrine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Chlorpheniramine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Cisapride: (Contraindicated) QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Because of the potential for TdP, use of other drugs that might increase the QT interval is contraindicated with cisapride. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Cocaine: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Codeine; Phenylephrine; Promethazine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Desloratadine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Dexbrompheniramine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Dextroamphetamine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and amphetamine; dextroamphetamine use. Concomitant use may potentiate sympathetic effects.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Dichlorphenamide: (Moderate) Use dichlorphenamide and albuterol together with caution. Metabolic acidosis has been reported with dichlorphenamide and albuterol aerosol and inhalation solution. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
    Dicyclomine: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Diethylpropion: (Major) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Digoxin: (Moderate) Mean decreases of 16% and 22% in serum digoxin levels were demonstrated after single-dose intravenous and oral administration of racemic albuterol, respectively, to normal volunteers who had received digoxin for 10 days. The clinical significance of these findings for patients with obstructive airway disease who are receiving albuterol or levalbuterol and digoxin on a chronic basis is unclear. The manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of albuterol or levalbuterol. Continue monitoring during concomitant treatment and increase the digoxin dose by 20 to 40% as necessary.
    Diphenhydramine; Phenylephrine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Diphenoxylate; Atropine: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Dobutamine: (Major) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Dopamine: (Major) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Dorzolamide; Timolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Doxapram: (Major) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Ephedrine: (Major) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Ephedrine; Guaifenesin: (Major) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and epinephrine use. Concomitant use may potentiate sympathetic effects.
    Ergotamine; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Esmolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Ethacrynic Acid: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
    Fexofenadine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Flavoxate: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Furosemide: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
    Glycopyrrolate: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Glycopyrrolate; Formoterol: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Glycopyrronium: (Moderate) Although ipratropium and glycopyrronium are minimally absorbed into the systemic circulation, there is the potential for additive anticholinergic effects if these drugs are administered together. Per the manufaturer, avoid concomitant administration of glycopyrronium with other anticholinergic medications.
    Green Tea: (Moderate) Some green tea products contain caffeine, which is a CNS-stimulant. Additive effects are expected if used in combination with other CNS stimulants including the beta-agonists.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Guaifenesin; Phenylephrine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Guaifenesin; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Homatropine; Hydrocodone: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Hydrocodone; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Hyoscyamine: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Ibuprofen; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Indacaterol; Glycopyrrolate: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Isocarboxazid: (Moderate) Use beta-agonists with caution in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with MAOIs because the action of beta-agonists on the cardiovascular system may be potentiated.
    Isoproterenol: (Major) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Labetalol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Levobetaxolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Levobunolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Levothyroxine: (Moderate) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
    Levothyroxine; Liothyronine (Porcine): (Moderate) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
    Levothyroxine; Liothyronine (Synthetic): (Moderate) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
    Lidocaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and epinephrine use. Concomitant use may potentiate sympathetic effects.
    Linezolid: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Liothyronine: (Moderate) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
    Lisdexamfetamine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and lisdexamfetamine use. Concomitant use may potentiate sympathetic effects.
    Loop diuretics: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
    Loratadine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Methacholine: (Major) Discontinue use of ipratropium 12 hours before a methacholine challenge test. Ipratropium inhibits the airway response to methacholine. (Major) Discontinue use of short-acting beta-agonists 6 hours before a methacholine challenge test. Beta-agonists inhibit the airway response to methacholine.
    Methamphetamine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Methazolamide: (Moderate) Albuterol may cause additive hypokalemia when coadministered with carbonic anhydrase inhibitors. These combinations can lead to symptomatic hypokalemia and associated ECG changes in some susceptible individuals. Monitoring of potassium levels would be advisable.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Methscopolamine: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Metoprolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Midodrine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Mobocertinib: (Minor) QT/QTc prolongation can occur with concomitant use of mobocertinib and short-acting beta-agonists although the risk of developing torsade de pointes (TdP) is low. Additional steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, may be considered in patients with additional risk factors for TdP. The risk for QT/QTc prolongation may be greater with long-acting beta-agonists than short-acting beta-agonists.
    Monoamine oxidase inhibitors: (Moderate) Use beta-agonists with caution in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with MAOIs because the action of beta-agonists on the cardiovascular system may be potentiated.
    Nadolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Naproxen; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Nebivolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Nebivolol; Valsartan: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Norepinephrine: (Major) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Oxybutynin: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Penbutolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Phendimetrazine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Phenelzine: (Moderate) Use beta-agonists with caution in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with MAOIs because the action of beta-agonists on the cardiovascular system may be potentiated.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Phentermine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and phentermine use. Concomitant use may potentiate sympathetic effects.
    Phentermine; Topiramate: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and phentermine use. Concomitant use may potentiate sympathetic effects.
    Phenylephrine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Pindolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Prilocaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and epinephrine use. Concomitant use may potentiate sympathetic effects.
    Procarbazine: (Major) Procarbazine has MAOI activity and the cardiovascular effects of beta-2 agonists may be potentiated by concomitant use of MAOIs. Although no data are available, procarbazine may interact similarly. Close observation for such effects is prudent, particularly if beta-agonists are administered within two weeks of stopping the MAOI.
    Promethazine; Phenylephrine: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Propantheline: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Propranolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Pseudoephedrine; Triprolidine: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
    Racepinephrine: (Major) Racepinephrine is a sympathomimetic drug with agonist actions at both the alpha and beta receptors. Patients using prescription beta-agonists for the treatment of asthma should generally avoid the concurrent use of racepinephrine inhalation since additive cardiovascular and nervous system adverse effects are possible, some which may be undesirable.
    Rasagiline: (Moderate) The concomitant use of rasagiline and sympathomimetic agents was not allowed in clinical studies; therefore, caution is advised during concurrent use of rasagiline and respiratory adrenergic agents (e.g., the beta-agonists). Although sympathomimetic agents are contraindicated for use with traditional non-selective monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with rasagiline because of the selective monoamine oxidase-B (MAO-B) inhibition of rasagiline at manufacturer recommended doses. However, the cardiovascular effects of beta-2 agonists may be potentiated by concomitant use of MAOIs. At least one case of hypertension occurred in a patient with previous episodes of high blood pressure who was receiving albuterol and selegiline, a selective MAOI related to rasagiline, concurrently. Close observation for such effects is prudent, particularly if beta-2 agonists are administered during or within 2 weeks of use of an MAOI.
    Scopolamine: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Theophylline, Aminophylline: (Moderate) Beta-agonists are commonly used in conjunction with aminophylline or theophylline therapy. Concomitant use can cause additive CNS stimulation; some patients may experience tremor or nervousness with combined use. More serious effects are rare, but may result in additive cardiovascular effects such as increased blood pressure and heart rate. Methylxanthine derivatives, ((e.g., theophylline and aminophylline) may rarely aggravate the hypokalemic effect seen with beta-agonists. Consider checking potassium levels if clinically indicated. (Moderate) Beta-agonists are commonly used in conjunction with aminophylline or theophylline therapy. Concomitant use can cause additive CNS stimulation; some patients may experience tremor or nervousness with combined use. More serious effects are rare, but may result in additive cardiovascular effects such as increased blood pressure and heart rate. Methylxanthine derivatives, (e.g., theophylline, aminophylline) may rarely aggravate the hypokalemic effect seen with beta-agonists. Consider checking potassium levels if clinically indicated.
    Thiazide diuretics: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
    Thyroid hormones: (Moderate) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
    Timolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
    Torsemide: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
    Tranylcypromine: (Moderate) Use beta-agonists with caution in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with MAOIs because the action of beta-agonists on the cardiovascular system may be potentiated.
    Trihexyphenidyl: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no available data on the presence of ipratropium; albuterol combinations, or its components, ipratropium bromide or albuterol, in human milk, the effects on the breastfed infant, or the effects on milk production. Ipratropium and albuterol concentrations in human breast milk are likely to be low. Caution should be exercised in lactating mothers who may require ipratropium; albuterol combinations. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. According to the 2004 recommendations of the National Asthma Education and Prevention Program (NAEPP) for managing asthma during pregnancy, there is currently no contraindication for use of short-acting inhaled beta-2 agonists during lactation.

    MECHANISM OF ACTION

    The synergistic effects of ipratropium; albuterol inhalation are likely due to the combined pharmacologic effects on the muscarinic and beta2-adrenergic receptors in the lung as opposed to any pharmacokinetic mechanism. Serial FEV1 measurements demonstrate that the combination ipratropium; albuterol inhalation produces greater improvement in pulmonary function than either ipratropium bromide or albuterol sulfate when given separately.
    Ipratropium: Ipratropium antagonizes the action of acetylcholine by blocking muscarinic cholinergic receptors that are present in the airways and other body organs. The actions of ipratropium parallel those of atropine on the bronchial smooth muscle, salivary glands, GI tract, and heart when administered by the intravenous route. When administered by oral inhalation, however, ipratropium exhibits greater antimuscarinic activity on the bronchial smooth muscle; systemic effects are minimal. By antagonizing the action of acetylcholine at the muscarinic receptor, ipratropium prevents the increase in intracellular concentration of cyclic guanosine monophosphate (cyclic GMP) associated with increased tone of bronchial smooth muscle. The end result of these actions is bronchodilation.
    Albuterol: Albuterol is a moderately selective beta2-adrenergic agonist that stimulates receptors of the smooth muscle in the lungs, uterus, and vasculature supplying skeletal muscle. The net result of albuterol binding to beta2-receptors in the lungs is relaxation of bronchial smooth muscles, which in turn relieves bronchospasm, reduces airway resistance, facilitates mucous drainage, and increases vital capacity. Albuterol can also inhibit the degranulation and subsequent release of inflammatory autocoids from mast cells. Intracellularly, the actions of albuterol are mediated by cAMP, the production of which is augmented by beta-stimulation. Albuterol is believed to work by activating adenylate cyclase, the enzyme responsible for generating cAMP, the intracellular mediator. Stimulation of beta2-receptors on peripheral vascular smooth muscle can cause vasodilation and a modest decrease in diastolic blood pressure. Albuterol may cause reflex tachycardia with higher than usual dosages. Beta2-adrenergic stimulation also may promote an intracellular shift of serum potassium leading to temporary hypokalemia. This effect is possibly due to stimulation of sodium-potassium ATPase.

    PHARMACOKINETICS

    Ipratropium; albuterol combinations are administered by oral inhalation.
     
    Ipratropium: The elimination half-life for ipratropium is about 2 hours after inhalation administration. It is partially metabolized to inactive ester hydrolysis products.
    Albuterol: Albuterol is conjugatively metabolized in the liver to albuterol 4'-O-sulfate. Seventy-percent of an inhaled dose is excreted unchanged in the urine (30%) or as metabolites in the feces (10%) and urine within 24 hours. The mean terminal half-life of albuterol is roughly 4 hours.

    Inhalation Route

    The coadministration of ipratropium bromide and albuterol sulfate from a single canister/vial does not significantly alter the systemic absorption of either component. Ipratropium bromide is not readily absorbed into the systemic circulation after inhalation either from the surface of the lung or from the gastrointestinal tract as confirmed by blood level and renal excretion studies. Plasma levels of ipratropium bromide are usually below the limits of assay detection; ipratropium does not cross the blood-brain barrier. After inhalation, albuterol is rapidly and completely absorbed; peak plasma albuterol concentrations are obtained within three hours after inhalation administration. Albuterol crosses the blood-brain barrier and placenta.
     
    The pharmacokinetics of Combivent inhalation aerosol was compared to that of Combivent Respimat inhalation spray in a 12-week randomized, double-blind, double-dummy parallel group trial of 108 US patients with COPD. Although the plasma ipratropium concentrations were low (average peak plasma concentration of 33.5 pg/ml) in patients receiving Combivent Respimat, the steady state systemic exposures (AUCs) obtained for ipratropium bromide following either drug product were comparable. Ipratropium plasma AUC and total amount of drug excreted unchanged in urine (Ae) ratios for Combivent Respimat and Combivent inhalation aerosol were 1.04 and 1.18, respectively. The steady-state systemic exposure (AUC) for albuterol was less from Combivent Respimat compared to that of Combivent inhalation aerosol. Albuterol plasma AUC and urine Ae ratios for Combivent Respimat and Combivent inhalation aerosol were 0.74 and 0.86, respectively.