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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 beta-agonist (SABA, albuterol), with a short-acting antimuscarinic agent (ipratropium)
    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 100 mcg of albuterol (equivalent to 120 mcg of albuterol sulfate) and 20 mcg of ipratropium bromide (monohydrate). 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] Albuterol; ipratropium 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. Albuterol; ipratropium 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 3 mg albuterol sulfate (2.5 mg of albuterol base) and 0.5 mg of ipratropium. Up to 2 additional doses may be allowed per day, if needed. Max: 6 vials/day via nebulizer. Additional doses or increased frequency of administration have not been studied. The safety and efficacy of extra doses of albuterol or ipratropium 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, albuterol; ipratropium may be used in Group A patients and may also be used in Groups B, C, and D for additional symptom control. Albuterol; ipratropium may also 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 asthma exacerbation†.
    Nebulizer Inhalation dosage (solution for nebulization; e.g., DuoNeb)
    Adults

    3 mL (containing 2.5 mg albuterol; 0.5 mg ipratropium bromide per 3 mL) via nebulizer every 20 minutes for 3 doses, then as needed (usually every 4 to 6 hours). Ipratropium may provide additive benefit to short-acting beta-2-agonists (SABAs) during early treatment of severe asthma exacerbation in the emergency department (ED) 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

    3 mL (2.5 mg albuterol; 0.5 mg ipratropium bromide per 3 mL), via 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 SABA once a patient is hospitalized are lacking.

    Children 6 to 12 years

    1.5 mL (1.25 mg albuterol; 0.25 mg ipratropium bromide) or 3 mL (2.5 mg albuterol; 0.5 mg ipratropium bromide per 3 mL) via 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 SABA once a child is hospitalized are lacking.

    Infants and Children 0 to 5 years

    1.5 mL (1.25 mg albuterol; 0.25 mg ipratropium bromide per 1.5 mL) via nebulizer every 20 minutes for 3 doses only (up to 1 hour) has been recommended for moderate to severe asthma exacerbation in the emergency care setting in patients with poor response to initial 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 <= 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 albuterol; ipratropium 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 your 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 the patient 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 with a damp cloth or tissue only, at least 1 time a week; 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 at 77 degrees F; excursions permitted to 59-86 degrees F
    DuoNeb:
    - After removing from pouch, use product within one week
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Protect from light
    - Store between 36 to 77 degrees F
    - Store unused product in foil pouch

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    The Combivent albuterol; ipratropium 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

    Albuterol; ipratropium aerosols can produce a paradoxical bronchospasm that can be life-threatening in some patients. If bronchospasm occurs, the albuterol; ipratropium 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 albuterol or ipratropium. Albuterol; ipratropium combinations are contraindicated in patients with atropine hypersensitivity, albuterol hypersensitivity, or their respective derivatives (e.g., levalbuterol hypersensitivity and respiratory antimuscarinic hypersensitivity).

    Alcoholism, bradycardia, cardiac arrhythmias, cardiac disease, coronary artery disease, females, heart failure, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, long QT syndrome, malnutrition, myocardial infarction, QT prolongation

    Beta agonists have been reported to produce ECG changes, such as flattening of the T-wave, QT prolongation, and ST segment depression. Use albuterol; ipratropium with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, congenital long QT syndrome, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, elderly patients, patients with diabetes, thyroid dysfunction, malnutrition, alcoholism, or hepatic dysfunction may also be at increased risk for QT prolongation. At excessive use or dosages, beta-agonists may produce a transient hypokalemia, which might produce adverse effects in susceptible individuals with cardiac disease, particularly those patients on non-potassium sparing diuretics.

    Anticholinergic medications, bladder obstruction, prostatic hypertrophy, urinary retention

    Due to the anticholinergic effects of ipratropium, albuterol; ipratropium 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.

    Geriatric

    Clinical studies of albuterol; ipratropium inhalers and nebulizer solutions have included a fair percentage of older adults 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. Geater 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.

    Diabetes mellitus, hyperthyroidism, pheochromocytoma, seizure disorder, seizures, thyroid disease, thyrotoxicosis

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

    Closed-angle glaucoma, contact lenses, ophthalmic administration

    Due to the anticholinergic effects of ipratropium, albuterol; ipratropium 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 albuterol; ipratropium 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.

    Labor, obstetric delivery, pregnancy

    There are no randomized clinical studies of albuterol; ipratropium inhalation combinations, or its individual components, ipratropium bromide and albuterol sulfate, in pregnant women. In animals, a small increase in craniofacial defects, including cleft palate formation has been seen with systemically administered albuterol. Most adverse effects observed in human pregnancy are a result of the cardiovascular and metabolic effects of albuterol. Maternal and fetal tachycardia and maternal hypotension have occurred with systemic use of the beta-agonists. Several studies of inhaled beta-agonist use during pregnancy have not noted an increase in either congenital malformations or other adverse perinatal outcomes. Ipratropium is negligibly absorbed systemically following oral inhalation; therefore, maternal use is not expected to result in fetal exposure to the drug. Published literature over several decades, including cohort studies, case-control studies, and case series have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes with ipratropium bromide. Due to the potential for interference with uterine contractility, the use of albuterol; ipratropium 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 albuterol; ipratropium 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 albuterol; ipratropium 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.

    Children, infants

    The safety and effectiveness of albuterol; ipratropium fixed-dose combinations has not been established in infants and children.

    Hepatic disease, renal disease, renal failure, renal impairment

    The use of albuterol; ipratropium has not been adequately studied in patients with renal impairment (including renal failure, renal disease) or hepatic disease.

    MAOI therapy

    Beta2-agonists should be administered with extreme caution to patients being treated with MAOI therapy (see Drug Interactions).

    Driving or operating machinery

    Advise patients receiving albuterol; ipratropium to use caution when driving or operating machinery or when engaged in other activities that require balance and visual acuity as this medication may cause dizziness, accommodation disorder, mydriasis, and blurred vision.

    ADVERSE REACTIONS

    Severe

    arrhythmia exacerbation / Early / 0-2.0
    atrial fibrillation / Early / 0.5-0.5
    anaphylactoid reactions / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    bronchospasm / Rapid / Incidence not known
    laryngospasm / 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
    hypertension / Early / 0-2.0
    angina / Early / 0-2.0
    edema / Delayed / 0-2.0
    palpitations / Early / 0-2.0
    hypokalemia / Delayed / 0-2.0
    dysuria / Early / 0-2.0
    wheezing / Rapid / 0-2.0
    constipation / Delayed / 0-2.0
    stomatitis / Delayed / 0-2.0
    supraventricular tachycardia (SVT) / Early / 0.5-0.5
    dysphonia / Delayed / 1.0
    hypotension / Rapid / Incidence not known
    QT prolongation / Rapid / Incidence not known
    peripheral vasodilation / Rapid / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    corneal edema / Early / Incidence not known
    blurred vision / Early / Incidence not known
    conjunctival hyperemia / Early / Incidence not known
    urinary retention / 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
    dizziness / Early / 0-2.0
    ocular pain / Early / 0-2.0
    xerostomia / Early / 0-2.0
    fatigue / Early / 0-2.0
    insomnia / Early / 0-2.0
    tremor / Early / 0-2.0
    paresthesias / Delayed / 0-2.0
    anxiety / Delayed / 0-2.0
    diarrhea / Early / 0-2.0
    vomiting / Early / 0-2.0
    dysgeusia / Early / 0-2.0
    dyspepsia / Early / 0-2.0
    nausea / Early / 1.4-2.0
    asthenia / Delayed / 0-2.0
    arthralgia / Delayed / 0-2.0
    myalgia / Early / 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
    drowsiness / Early / Incidence not known
    mydriasis / Early / Incidence not known
    throat irritation / Early / Incidence not known
    nasal congestion / Early / Incidence not known
    nasal dryness / Early / Incidence not known
    hoarseness / Early / Incidence not known
    pyrosis (heartburn) / Early / Incidence not known
    flushing / Rapid / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    back pain / 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) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Acetaminophen; Butalbital; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Acetaminophen; Butalbital; Caffeine; Codeine: (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; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (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) 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; Phenylephrine; Phenyltoloxamine: (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; 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) 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; 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) 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.
    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) 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.
    Alfuzosin: (Minor) Use caution when administering alfuzosin with short-acting beta-agonists (SABAs) due to the potential for QT prolongation. Alfuzosin may prolong the QT interval in a dose-dependent manner. SABAs may rarely be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or if associated with hypokalemia.
    Amiodarone: (Minor) Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone Short-acting beta-agonists may rarely be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Amisulpride: (Minor) Monitor ECGs for QT prolongation when amisulpride is administered with short-acting beta-agonists. Amisulpride causes dose- and concentration- dependent QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be lower with short-acting beta-agonists as compared to long-acting beta-agonists.
    Amitriptyline: (Minor) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia.
    Amitriptyline; Chlordiazepoxide: (Minor) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia.
    Amoxicillin; Clarithromycin; Lansoprazole: (Minor) The coadministration of beta-agonists with clarithromycin may increase the risk for adverse effects, including prolongation of the QT interval. The action of beta-agonists on the cardiovascular system may be potentiated by clarithromycin. Clarithromycin is a strong CYP3A4 inhibitor and the co-administration of salmeterol or indacaterol with strong CYP3A4 inhibitors can result in elevated concentrations and increased risk for potential cardiovascular adverse effects. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Amoxicillin; Clarithromycin; Omeprazole: (Minor) The coadministration of beta-agonists with clarithromycin may increase the risk for adverse effects, including prolongation of the QT interval. The action of beta-agonists on the cardiovascular system may be potentiated by clarithromycin. Clarithromycin is a strong CYP3A4 inhibitor and the co-administration of salmeterol or indacaterol with strong CYP3A4 inhibitors can result in elevated concentrations and increased risk for potential cardiovascular adverse effects. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Amphetamine: (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.
    Amphetamine; Dextroamphetamine Salts: (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.
    Amphetamine; Dextroamphetamine: (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.
    Anagrelide: (Minor) Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. Torsades de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Beta-agonists may rarely be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    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.
    Apomorphine: (Minor) Beta-agonists should be used cautiously with apomorphine. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Aripiprazole: (Minor) Use caution if administering aripiprazole with other drugs that may cause QT prolongation, including the short-acting beta-agonists (SABAs). QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. SABAs may rarely cause adverse cardiovascular effects such as QT prolongation, usually at higher doses and/or when associated with hypokalemia.
    Arsenic Trioxide: (Minor) Beta-agonists should be used cautiously and with close monitoring with arsenic trioxide. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Avoid concomitant use of arsenic trioxide with other drugs that may cause QT interval prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Artemether; Lumefantrine: (Minor) The administration of artemether; lumefantrine is associated with prolongation of the QT interval. Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation and should be avoided. Consider ECG monitoring if other QT prolonging drugs must be used with or after artemether; lumefantrine treatment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Articaine; Epinephrine: (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.
    Asenapine: (Minor) Asenapine has been associated with QT prolongation. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents also known to have this effect. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    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; Dihydrocodeine: (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) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Atenolol; Chlorthalidone: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Atomoxetine: (Minor) Use caution when using atomoxetine in combination with short-acting beta-agonists as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonistsas compared to short-acting beta-agonists.
    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; Diphenoxylate: (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.
    Atropine; Hyoscyamine; Phenobarbital; 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.
    Azithromycin: (Major) Avoid coadministration of azithromycin with short-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Bedaquiline: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with beta-agonists. Bedaquiline has been reported to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (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) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    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) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Betaxolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Minor) QT/QTc prolongation can occur with concomitant use of short-acting beta-agonists and metronidazole 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
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) QT/QTc prolongation can occur with concomitant use of short-acting beta-agonists and metronidazole 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
    Bisoprolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Brimonidine; Timolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Brompheniramine; Carbetapentane; 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; 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; Hydrocodone; Pseudoephedrine: (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) 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.
    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) Loop diuretics may potentiate hypokalemia and ECG changes seen with beta agonists. Hypokalemia due to beta agonists appears to be dose related and is more likely with high dose therapy. Caution is advised when loop diuretics are coadministered with high doses of beta agonists; potassium levels may need to be monitored.
    Buprenorphine: (Minor) Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Buprenorphine; Naloxone: (Minor) Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Cabotegravir; Rilpivirine: (Minor) Caution is advised when administering rilpivirine with short-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Caffeine; Ergotamine: (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.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; Phenylephrine; Pyrilamine: (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.
    Carbetapentane; Pseudoephedrine: (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; Dextromethorphan; Pseudoephedrine: (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; Hydrocodone; 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; Hydrocodone; Pseudoephedrine: (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; 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) 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.
    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) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Carvedilol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Ceritinib: (Minor) Periodically monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and long-acting beta-agonists; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Cetirizine; Pseudoephedrine: (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.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (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.
    Chlophedianol; 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.
    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.
    Chloroquine: (Major) Avoid coadministration of chloroquine with short-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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; 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; Dihydrocodeine; Pseudoephedrine: (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; Guaifenesin; Hydrocodone; Pseudoephedrine: (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; Hydrocodone; 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; Hydrocodone; Pseudoephedrine: (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; 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) 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.
    Chlorpromazine: (Minor) Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with chlorpromazine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Ciprofloxacin: (Minor) Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ciprofloxacin include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    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.
    Citalopram: (Minor) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with citalopram include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Clarithromycin: (Minor) The coadministration of beta-agonists with clarithromycin may increase the risk for adverse effects, including prolongation of the QT interval. The action of beta-agonists on the cardiovascular system may be potentiated by clarithromycin. Clarithromycin is a strong CYP3A4 inhibitor and the co-administration of salmeterol or indacaterol with strong CYP3A4 inhibitors can result in elevated concentrations and increased risk for potential cardiovascular adverse effects. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Clofazimine: (Minor) Monitor ECGs for QT prolongation when clofazimine is administered with short-acting beta-agonists. QT prolongation and torsade de pointes have been reported in patients receiving clofazimine in combination with QT prolonging medications. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be lower with short-acting beta-agonists as compared to long-acting beta-agonists.
    Clomipramine: (Minor) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia.
    Clozapine: (Minor) Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. The manufacturer of clozapine recommends caution during concurrent use with medications known to cause QT prolongation. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with clozapine include the beta-agonists. 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; 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. (Minor) Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Use cautiously with promethazine, which has been reported to cause QT prolongation.
    Codeine; Promethazine: (Minor) Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Use cautiously with promethazine, which has been reported to cause QT prolongation.
    Crizotinib: (Minor) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving crizotinib concomitantly with short-acting beta-agonists. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Dasatinib: (Minor) Use dasatinib with caution in combination with beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Degarelix: (Minor) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving short-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Desipramine: (Minor) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia.
    Desloratadine; Pseudoephedrine: (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.
    Deutetrabenazine: (Minor) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and short-acting beta-agonists. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (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.
    Dextroamphetamine: (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; 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) 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; Promethazine: (Minor) Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Use cautiously with promethazine, which has been reported to cause QT prolongation.
    Dextromethorphan; Quinidine: (Minor) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    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.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (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.
    Diphenhydramine; Hydrocodone; 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.
    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.
    Disopyramide: (Minor) Beta-agonists should be used cautiously and with close monitoring with disopyramide. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    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.
    Dofetilide: (Minor) Coadministration of dofetilide and short-acting beta-agonists may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Dolasetron: (Minor) Administer dolasetron with caution in combination with short-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
    Dolutegravir; Rilpivirine: (Minor) Caution is advised when administering rilpivirine with short-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Donepezil: (Minor) Use donepezil with caution in combination with short-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Donepezil; Memantine: (Minor) Use donepezil with caution in combination with short-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    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.
    Doxepin: (Minor) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia.
    Dronedarone: (Contraindicated) Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. The concomitant use of dronedarone with other drugs that prolong the QTc may induce Torsade de Pointes (TdP) and is contraindicated. Contraindicated drugs include the beta-agonists.
    Droperidol: (Minor) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). In December 2001, the FDA issued a black box warning regarding the use of droperidol and its association with QT prolongation and potential for cardiac arrhythmias based on post-marketing surveillance data. According to the revised 2001 labeling for droperidol, any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with droperidol include beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Efavirenz: (Minor) Consider alternatives to efavirenz when coadministering with short-acting beta-agonists. QTc prolongation has been observed with the use of efavirenz. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Efavirenz; Emtricitabine; Tenofovir: (Minor) Consider alternatives to efavirenz when coadministering with short-acting beta-agonists. QTc prolongation has been observed with the use of efavirenz. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Minor) Consider alternatives to efavirenz when coadministering with short-acting beta-agonists. QTc prolongation has been observed with the use of efavirenz. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Eliglustat: (Minor) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include beta-agonists.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Minor) Caution is advised when administering rilpivirine with short-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Minor) Caution is advised when administering rilpivirine with short-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Encorafenib: (Minor) If encorafenib is coadministered with a short-acting beta-agonist, consider monitoring ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Enflurane: (Minor) Enflurane, like other halogenated anesthetics, can prolong the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously with halogenated anesthetics include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. The action of beta-agonists on the cardiovascular system may be potentiated by a halogenated anesthetic. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Entrectinib: (Minor) Coadministration of entrectinib and short-acting beta-agonists may increase the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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) 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.
    Eribulin: (Minor) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Erythromycin: (Minor) Erythromycin administration is associated with QT prolongation and torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with erythromycin include the beta-agonists. The effects of these beta-agonists on the cardiovascular system may be potentiated. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia.
    Erythromycin; Sulfisoxazole: (Minor) Erythromycin administration is associated with QT prolongation and torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with erythromycin include the beta-agonists. The effects of these beta-agonists on the cardiovascular system may be potentiated. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia.
    Escitalopram: (Minor) Use escitalopram with caution in combination with short-acting beta agonists as concurrent use may increase the risk of QT prolongation. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with escitalopram. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Esmolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Ethacrynic Acid: (Moderate) Loop diuretics may potentiate hypokalemia and ECG changes seen with beta agonists. Hypokalemia due to beta agonists appears to be dose related and is more likely with high dose therapy. Caution is advised when loop diuretics are coadministered with high doses of beta agonists; potassium levels may need to be monitored.
    Ezogabine: (Minor) Use caution during concurrent use of ezogabine and short-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Ezogabine has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fexofenadine; Pseudoephedrine: (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.
    Fingolimod: (Minor) Fingolimod initiation results in decreased heart rate and the drug may prolong the QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of torsade de pointes (TdP). Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, however, drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with fingolimod include the beta-agonists.
    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.
    Flecainide: (Minor) Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with flecainide include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Fluconazole: (Minor) Use fluconazole with caution in combination with beta-agonists as concurrent use may increase the risk of QT prolongation. Fluconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluoxetine: (Minor) Use fluoxetine with caution in combination with short-acting beta-agonists. Coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation and TdP have been reported in patients treated with fluoxetine. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluoxetine; Olanzapine: (Minor) Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation. Drugs with a possible risk for QT prolongation include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. (Minor) Use fluoxetine with caution in combination with short-acting beta-agonists. Coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation and TdP have been reported in patients treated with fluoxetine. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluphenazine: (Minor) Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. This risk is generally higher at elevated drugs concentrations of phenothiazines. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with fluphenazine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Fluvoxamine: (Minor) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and short-acting beta-agonists. Coadminister with caution. QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists compared to short-acting beta-agonists.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as short-acting beta-agonists. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Fostemsavir: (Minor) Use beta-agonists and fostemsavir together with caution due to the potential for QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
    Furosemide: (Moderate) Loop diuretics may potentiate hypokalemia and ECG changes seen with beta agonists. Hypokalemia due to beta agonists appears to be dose related and is more likely with high dose therapy. Caution is advised when loop diuretics are coadministered with high doses of beta agonists; potassium levels may need to be monitored.
    Gemifloxacin: (Minor) Use gemifloxacin and short-acting beta-agonists together with caution due to increased risk for QT prolongation and torsade de pointes (TdP). Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Gemtuzumab Ozogamicin: (Minor) Coadministration of gemtuzumab ozogamicin with short-acting beta-agonists may increase the potential for additive QT prolongation and risk of torsade de pointes (TdP). Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Gilteritinib: (Minor) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and a short-acting beta-agonist is necessary. Gilteritinib has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Glasdegib: (Minor) Consider increased frequency of ECG monitoring if coadministration of glasdegib and short-acting beta-agonists is necessary. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    Goserelin: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving short-acting beta-agonists. Androgen deprivation therapy may prolong the QT/QTc interval. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Granisetron: (Minor) Use granisetron with caution in combination with short-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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) 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; 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) 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.
    Halofantrine: (Contraindicated) Halofantrine is considered to have a well-established risk for QT prolongation and torsade de pointes (TdP). Halofantrine should be avoided in patients receiving drugs which may induce QT prolongation. These drugs include the beta-agonists. Beta-agonists may be associated with cardiovascular effects, usually at higher doses and/or when associated with hypokalemia.
    Haloperidol: (Minor) Caution is advisable when combining haloperidol concurrently with short-acting beta-agonists as concurrent use may increase the risk of QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Halothane: (Minor) Halothane, like other halogenated anesthetics, can prolong the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously with halogenated anesthetics include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. The action of beta-agonists on the cardiovascular system may be potentiated by a halogenated anesthetic.
    Histrelin: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving short-acting beta-agonists. Androgen deprivation therapy may prolong the QT/QTc interval. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Hydrocodone; 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.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (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.
    Hydrocodone; Pseudoephedrine: (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.
    Hydroxychloroquine: (Major) Avoid coadministration of short-acting beta-agonists and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Hydroxyzine: (Minor) Caution is recommended if hydroxyzine is administered with short-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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) 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.
    Ibutilide: (Minor) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Iloperidone: (Minor) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. Drugs with a possible risk for QT prolongation that should be avoided with iloperidone include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Imipramine: (Minor) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia.
    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.
    Inotuzumab Ozogamicin: (Minor) Coadministration of inotuzumab ozogamicin with short-acting beta-agonists may increase the potential for additive QT prolongation and risk of torsade de pointes (TdP). Inotuzumab has been associated with QT interval prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Isocarboxazid: (Major) Beta-agonists should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors (MAOIs) due to their sympathomimetic effects. Weigh the risks of coadministration, and where possible, allow a washout period after discontinuation of the MAOI before instituring beta-agonist treatment or vice-versa. The cardiovascular effects of beta-agonists may be potentiated by concomitant use of MAOIs. Close observation for such effects is prudent, particularly if beta-agonists are administered within 2 weeks of stopping the MAOI. Monitor blood pressure and heart rate.
    Isoflurane: (Minor) Isoflurane, like other halogenated anesthetics, can prolong the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously with halogenated anesthetics include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. The action of beta-agonists on the cardiovascular system may be potentiated by a halogenated anesthetic.
    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.
    Itraconazole: (Minor) Use itraconazole with caution in combination with beta-agonists as concurrent use may increase the risk of QT prolongation. Itraconazole has been associated with prolongation of the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Ivosidenib: (Minor) Coadministration of ivosidenib with short-acting beta-agonists may increase the risk of QT prolongation. If concomitant use is necessary, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Ketoconazole: (Minor) Coadministration may increase the risk of QT prolongation. Ketoconazole has been associated with prolongation of the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists such as albuterol.
    Labetalol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Lapatinib: (Minor) Monitor for evidence of QT prolongation if lapatinib is administered with short-acting beta-agonists. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Lefamulin: (Minor) Coadministration of lefamulin and short-acting beta-agonists may increase the risk of QT prolongation. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Lenvatinib: (Minor) Beta-agonists should be used cautiously and with close monitoring with lenvatinib. QT prolongation was reported in patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) in a double-blind, randomized, placebo-controlled clinical trial after receiving lenvatinib daily at the recommended dose; the QT/QTc interval was not prolonged, however, after a single 32 mg dose (1.3 times the recommended daily dose) in healthy subjects. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Leuprolide: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving short-acting beta-agonists. Androgen deprivation therapy may prolong the QT/QTc interval. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Leuprolide; Norethindrone: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving short-acting beta-agonists. Androgen deprivation therapy may prolong the QT/QTc interval. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Levobetaxolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Levobunolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Levofloxacin: (Minor) Levofloxacin should be used cautiously with short-acting beta-agonists as concurrent use may increase the risk for QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. Levofloxacin has been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of levofloxacin.
    Levomethadyl: (Contraindicated) Levomethadyl is associated with an established risk of QT prolongation and/or torsade de pointes, particularly at high drug concentrations. Levomethadyl is contraindicated in combination with other agents that may prolong the QT interval. Agents with potential to prolong the QT interval include the beta agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Levothyroxine: (Moderate) Based on the cardiovascular stimulatory effects of beta-agonists and other sympathomimetics, concomitant use with thyroid hormones might enhance the effects on the cardiovascular system. 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) Based on the cardiovascular stimulatory effects of beta-agonists and other sympathomimetics, concomitant use with thyroid hormones might enhance the effects on the cardiovascular system. 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) Based on the cardiovascular stimulatory effects of beta-agonists and other sympathomimetics, concomitant use with thyroid hormones might enhance the effects on the cardiovascular system. 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.
    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) Based on the cardiovascular stimulatory effects of beta-agonists and other sympathomimetics, concomitant use with thyroid hormones might enhance the effects on the cardiovascular system. 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) 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.
    Lithium: (Minor) Lithium should be used cautiously and with close monitoring with beta-agonists. Lithium has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Lofexidine: (Minor) Monitor ECG if lofexidine is coadministered with short-acting beta-agonists due to the potential for additive QT prolongation. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be lower with short-acting beta-agonists as compared to long-acting beta-agonists.
    Loop diuretics: (Moderate) Loop diuretics may potentiate hypokalemia and ECG changes seen with beta agonists. Hypokalemia due to beta agonists appears to be dose related and is more likely with high dose therapy. Caution is advised when loop diuretics are coadministered with high doses of beta agonists; potassium levels may need to be monitored.
    Loperamide: (Minor) Coadministration of loperamide with beta-agonist may increase the risk for QT prolongation and torsade de pointes (TdP). At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP and cardiac arrest. Beta-agonists have also been associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Loperamide; Simethicone: (Minor) Coadministration of loperamide with beta-agonist may increase the risk for QT prolongation and torsade de pointes (TdP). At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP and cardiac arrest. Beta-agonists have also been associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with short-acting beta-agonists due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Loratadine; Pseudoephedrine: (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.
    Macimorelin: (Minor) Concurrent use of macimorelin with short-acting beta-agonists may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Maprotiline: (Minor) Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Drugs with a possible risk for QT prolongation that should be used cautiously with maprotiline include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT prolongation, usually at higher doses and/or when associated with hypokalemia.
    Mefloquine: (Minor) While there is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QT interval, mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously with mefloquine include the beta-agonists. Beta agonists may cause adverse cardiovascular effects, usually with higher doses or when associated with hypokalemia.
    Mepenzolate: (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.
    Meperidine; Promethazine: (Minor) Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Use cautiously with promethazine, which has been reported to cause QT prolongation.
    Mesoridazine: (Contraindicated) Mesoridazine is associated with an established risk of QT prolongation and/or torsade de pointes (TdP). Agents that prolong the QT interval could lead to torsade de pointes are contraindicated with mesoridazine and include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    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.
    Methadone: (Minor) The need to coadminister methadone with drugs known to prolong the QT interval should be done with extreme caution and a careful assessment of treatment risks versus benefits. Methadone is considered to be associated with an increased risk for QT prolongation and torsade de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). Methadone inhibits cardiac potassium channels and prolongs the QT interval. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with methadone include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    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) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Metronidazole: (Minor) QT/QTc prolongation can occur with concomitant use of short-acting beta-agonists and metronidazole 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
    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.
    Midostaurin: (Minor) Concomitant use may result in additive effects on the QT interval. In clinical trials, QT prolongation was reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Mifepristone: (Minor) Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Drugs with a possible risk for QT prolongation that should be used cautiously with mifepristone include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Mirtazapine: (Minor) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and short-acting beta-agonists. Coadminister with caution. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Monoamine oxidase inhibitors: (Major) Beta-agonists should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors (MAOIs) due to their sympathomimetic effects. Weigh the risks of coadministration, and where possible, allow a washout period after discontinuation of the MAOI before instituring beta-agonist treatment or vice-versa. The cardiovascular effects of beta-agonists may be potentiated by concomitant use of MAOIs. Close observation for such effects is prudent, particularly if beta-agonists are administered within 2 weeks of stopping the MAOI. Monitor blood pressure and heart rate.
    Moxifloxacin: (Minor) Prolongation of the QT interval has been reported with administration of moxifloxacin. Post-marketing surveillance has identified very rare cases of ventricular arrhythmias including torsade de pointes (TdP), usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. According to the manufacturer, moxifloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval. Drugs with a possible risk for QT prolongation include beta-agonists. Beta-agonists may cause adverse cardiovascular effects, usually at higher doses and/or when associated with hypokalemia.
    Nadolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Naproxen; Pseudoephedrine: (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.
    Nebivolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Nebivolol; Valsartan: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Nilotinib: (Minor) Coadministration of nilotinib with short-acting beta-agonists may increase the potential for additive QT prolongation. Sudden death and QT interval prolongation have occurred in patients who received nilotinib therapy. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    Norfloxacin: (Minor) Quinolones have been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during post-marketing surveillance of norfloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. Norfloxacin should be used cautiously with other agents that may prolong the QT interval such as the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Nortriptyline: (Minor) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia.
    Octreotide: (Minor) Use octreotide with caution in combination with short-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists [such as albuterol]. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Ofloxacin: (Minor) Ofloxacin should be used cautiously with short-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists [such as albuterol]. Quinolones have been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of ofloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Olanzapine: (Minor) Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation. Drugs with a possible risk for QT prolongation include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Ondansetron: (Minor) Ondansetron has been associated with QT prolongation and post-marketing reports of torsade de pointes (TdP). Among 42 patients receiving a 4 mg IV bolus dose of ondansetron for postoperative nausea and vomiting, the mean maximal QTc interval prolongation was 20 +/- 13 msec at the third minute after administration (p < 0.0001). Risk for QT prolongation increases with increased dosage, and a 32 mg IV dose must no longer be used for prevention of chemotherapy induced emesis. If ondansetron and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with ondansetron include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Osilodrostat: (Minor) Monitor ECGs in patients receiving osilodrostat with short-acting beta-agonists. Osilodrostat is associated with dose-dependent QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be lower with short-acting beta-agonists as compared to long-acting beta-agonists.
    Osimertinib: (Minor) Use osimertinib and short-acting beta-agonists together with caution due to the risk of QT prolongation. The manufacturer of osimertinib recommends avoiding coadministration with other drugs that prolong the QT, if possible; if unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes. An interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Oxaliplatin: (Minor) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists such as albuterol, levalbuterol, metaproterenol, pirbuterol, and terbutaline.
    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.
    Ozanimod: (Minor) Coadministration of ozanimod with short-acting beta-agonists may increase the potential for additive QT prolongation. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Paliperidone: (Minor) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. Drugs with a possible risk for QT prolongation that should be used cautiously with paliperidone include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Closely monitor patients with known risk factors for cardiac disease or arrhythmias during coadministration.
    Panobinostat: (Minor) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include beta-agonists.
    Pasireotide: (Minor) Use caution when using pasireotide in combination with beta-agonists as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Pazopanib: (Minor) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation that should be used cautiously with pazopanib include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Pemoline: (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.
    Penbutolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Pentamidine: (Minor) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) should be used cautiously with pentamidine. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QTprolongation, usually at higher doses and/or when associated with hypokalemia.
    Perphenazine: (Minor) Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with perphenazine include the beta-agonists. Beta-agonists may cause adverse cardiovascular effects such as QT prolongation, usually at higher doses and/or when associated with hypokalemia.
    Perphenazine; Amitriptyline: (Minor) Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with perphenazine include the beta-agonists. Beta-agonists may cause adverse cardiovascular effects such as QT prolongation, usually at higher doses and/or when associated with hypokalemia. (Minor) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia.
    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: (Major) Beta-agonists should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors (MAOIs) due to their sympathomimetic effects. Weigh the risks of coadministration, and where possible, allow a washout period after discontinuation of the MAOI before instituring beta-agonist treatment or vice-versa. The cardiovascular effects of beta-agonists may be potentiated by concomitant use of MAOIs. Close observation for such effects is prudent, particularly if beta-agonists are administered within 2 weeks of stopping the MAOI. Monitor blood pressure and heart rate.
    Phentermine: (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.
    Phentermine; Topiramate: (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.
    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.
    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. (Minor) Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Use cautiously with promethazine, which has been reported to cause QT prolongation.
    Pimavanserin: (Minor) Pimavanserin may cause QT prolongation and should be used with caution with beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP) and should not be used with other drugs that might prolong the QT interval. Because of the potential for TdP, use of beta-agonists with pimozide is contraindicated. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Pindolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Pitolisant: (Minor) Coadministration of pitolisant and short-acting beta-agonists may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Ponesimod: (Minor) Concomitant use of ponesimod and short-acting beta-agonist may increase the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Posaconazole: (Minor) Use posaconazole with caution in combination with short-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Prilocaine; Epinephrine: (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.
    Primaquine: (Minor) Exercise caution when administering primaquine in combination with short-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Primaquine is associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Procainamide: (Minor) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    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.
    Prochlorperazine: (Minor) Phenothiazines like prochlorperazine have been associated with a risk of QT prolongation. This risk is generally higher at elevated drugs concentrations. Agents that prolong the QT interval and that should be used cautiously with prochlorperazine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Promethazine: (Minor) Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Use cautiously with promethazine, which has been reported to cause QT prolongation.
    Propafenone: (Minor) Propafenone is a Class IC antiarrhythmic which increases the QT interval, but largely due to prolongation of the QRS interval.. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with propafenone include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    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) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Protriptyline: (Minor) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia.
    Pseudoephedrine: (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.
    Quetiapine: (Minor) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Quinidine: (Minor) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Quinine: (Minor) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    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.
    Ranolazine: (Minor) Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. The mean increase in QTc is about 6 milliseconds, measured at the Tmax of the maximum dosage (1000 mg PO twice daily). However, in 5% of the population studied, increases in the QTc of at least 15 milliseconds have been reported. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with ranolazine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    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.
    Relugolix: (Minor) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Relugolix; Estradiol; Norethindrone acetate: (Minor) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Ribociclib: (Minor) Coadministration may result in additive effects on the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval such as ribociclib. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Ribociclib; Letrozole: (Minor) Coadministration may result in additive effects on the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval such as ribociclib. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Rilpivirine: (Minor) Caution is advised when administering rilpivirine with short-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Risperidone: (Minor) Use risperidone and short-acting beta-agonists together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Romidepsin: (Minor) Romidepsin has been reported to prolong the QT interval. If romidepsin must be coadministered with another drug that prolongs the QT interval, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of serum electrolytes and the ECG at baseline and periodically during treatment. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with romidepsin include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Saquinavir: (Minor) Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsades de pointes (TdP). Avoid administering saquinavir boosted with ritonavir with other drugs that may prolong the QT interval, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations.
    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.
    Selpercatinib: (Minor) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with short-acting beta-agonists is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Sertraline: (Minor) Use caution and monitor patients for QT prolongation when administering short-acting beta-agonists with sertraline. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists versus short-acting beta-agonists. Sertraline's FDA-approved labeling recommends avoiding concomitant use with drugs known to prolong the QTc interval; however, the risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure).
    Sevoflurane: (Minor) Sevoflurane, like other halogenated anesthetics, can prolong the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously with halogenated anesthetics include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. The action of beta-agonists on the cardiovascular system may be potentiated by a halogenated anesthetic.
    Siponimod: (Minor) In general, do not initiate treatment with siponimod in patients receiving prochlorperazine due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be lower with short-acting beta-agonists compared to long-acting beta-agonists.
    Solifenacin: (Minor) Solifenacin has been associated dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with post-marketing use, although causality was not determined. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. The action of beta-agonists on the cardiovascular system may be potentiated.
    Sorafenib: (Minor) Use caution if coadministration of sorafenib with short-acting beta-agonists is necessary due to the risk of QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. Sorafenib is also associated with QTc prolongation.
    Sotalol: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Sunitinib: (Minor) Monitor patients for QT prolongation if coadministration of short-acting beta-agonists with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Tacrolimus: (Minor) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with a short-acting beta-agonist. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Tamoxifen: (Minor) Caution is advised with the concomitant use of tamoxifen and short-acting beta-agonists due to an increased risk of QT prolongation. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be lower with short-acting beta-agonists compared with long-acting beta-agonists.
    Telavancin: (Minor) Due to increased risk of QT interval prolongation and torsade de pointes (TdP), use caution if telavancin is administered with a beta-agonist. Telavancin has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Telithromycin: (Minor) Use caution if short-acting beta-agonists are administered with telithromycin as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Tetrabenazine: (Minor) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    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.
    Thioridazine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Because of the potential for QR prolongation, use of beta-agonists with thioridazine is contraindicated. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Thyroid hormones: (Moderate) Based on the cardiovascular stimulatory effects of beta-agonists and other sympathomimetics, concomitant use with thyroid hormones might enhance the effects on the cardiovascular system. 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) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients 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. 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.
    Tolterodine: (Minor) Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. This should be taken into consideration when prescribing tolterodine to patients taking other drugs that are associated with QT prolongation. Drugs with a possible risk for QT prolongation that should be used cautiously with tolterodine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Toremifene: (Minor) Use toremifene and short-acting beta-agonists together with caution due to the risk of QT prolongation. The manufacturer of toremifene recommends avoiding toremifene with other drugs that prolong the QT, if possible. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Torsemide: (Moderate) Loop diuretics may potentiate hypokalemia and ECG changes seen with beta agonists. Hypokalemia due to beta agonists appears to be dose related and is more likely with high dose therapy. Caution is advised when loop diuretics are coadministered with high doses of beta agonists; potassium levels may need to be monitored.
    Tranylcypromine: (Major) Beta-agonists should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors (MAOIs) due to their sympathomimetic effects. Weigh the risks of coadministration, and where possible, allow a washout period after discontinuation of the MAOI before instituring beta-agonist treatment or vice-versa. The cardiovascular effects of beta-agonists may be potentiated by concomitant use of MAOIs. Close observation for such effects is prudent, particularly if beta-agonists are administered within 2 weeks of stopping the MAOI. Monitor blood pressure and heart rate.
    Trazodone: (Minor) Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are post-marketing reports of torsade de pointes (TdP). Therefore, the manufacturer recommends avoiding trazodone in patients receiving other drugs that increase the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Coadministration with other drugs known to prolong the QT interval may potentiate the action of beta-agonists on the cardiovascular system.
    Triclabendazole: (Minor) Monitor ECGs in patients receiving triclabendazole with short-acting beta-agonists. Transient prolongation of the mean QTc interval was noted on the ECG recordings in dogs administered triclabendazole. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be lower with short-acting beta-agonists as compared to long-acting beta-agonists.
    Tricyclic antidepressants: (Minor) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia.
    Trifluoperazine: (Minor) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation that should be used cautiously with trifluoperazine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    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.
    Trimipramine: (Minor) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia.
    Triptorelin: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving short-acting beta-agonists. Androgen deprivation therapy may prolong the QT/QTc interval. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Vandetanib: (Minor) If concomitant use of vandetanib with short-acting beta-agonists is necessary, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Vardenafil: (Minor) Coadministration of vardenafil and short-acting beta-agonists may increase the risk of QT prolongation. Vardenafil has been associated with QT prolongation. Therapeutic and supratherapeutic doses of vardenafil can produce an increase in QTc interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Vemurafenib: (Minor) Vemurafenib has been associated with QT prolongation. If vemurafenib and another drug that is associated with a possible risk for QT prolongation and torsade de pointes (TdP) must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation that should be used cautiously with vemurafenib include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Venlafaxine: (Minor) Venlafaxine administration is associated with a possible risk of QT prolongation; torsade de pointes (TdP) has been reported with post-marketing use. Drugs with a possible risk for QT prolongation that should be used cautiously with venlafaxine include the beat-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Voclosporin: (Minor) Concomitant use of voclosporin and short-acting beta-agonists may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Voriconazole: (Minor) Voriconazole has been associated with QT prolongation and rare cases of torsade de pointes. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with voriconazole include the beta-agonists. In addiition, voriconazole is a CYP3A4 inhibitor and may cause elevated concentrations of salmeterol or indacaterol, which are metabolized by CYP3A4. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Vorinostat: (Minor) Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval, such as vorinostat, because the action of beta-agonists on the cardiovascular system may be potentiated.
    Ziprasidone: (Minor) Use these drugs together with caution. Beta-agonists may be associated with adverse cardiovascular effects including tachycardia and QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP).

    PREGNANCY AND LACTATION

    Pregnancy

    There are no available data on the presence of albuterol; ipratropium 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 albuterol; ipratropium 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.
    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.
    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.

    PHARMACOKINETICS

    Albuterol; ipratropium combinations are administered by oral inhalation.
     
    Albuterol: Unlike isoproterenol, albuterol is not a substrate for the cellular uptake processes for catecholamines nor is it metabolized by catechol-O-methyl transferase. Instead, the drug is conjugatively metabolized in the liver to albuterol 4'-O-sulfate. Seventy-percent of an inhaled albuterol 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.
    Ipratropium: The half-life of elimination for ipratropium is about 2 hours after inhalation administration. It is partially metabolized to inactive ester hydrolysis products.

    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. 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.
     
    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.
     
    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.