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    Respiratory Short-Acting Beta-2 Agonists (SABA)

    DEA CLASS

    Rx

    DESCRIPTION

    Inhaled short-acting beta-2 agonist (SABA); active R-enantiomer of racemic albuterol
    Used for acute bronchospams and asthma and prevention of bronchospasm or exercise-induced brochospasm in adults and pediatrics; also used in adults for treatment of COPD
    Available as nebulizer solutions or aerosol inhaler

    COMMON BRAND NAMES

    Xopenex, Xopenex Pediatric

    HOW SUPPLIED

    Levalbuterol/Levalbuterol Hydrochloride/Xopenex/Xopenex Pediatric Respiratory (Inhalation) Sol: 0.31mg, 0.5mL, 0.63mg, 1.25mg, 3mL
    Levalbuterol/Levalbuterol Tartrate/Xopenex Respiratory (Inhalation) Aer Met: 1actuation, 45mcg

    DOSAGE & INDICATIONS

    For the treatment of acute bronchospasm and bronchospasm prophylaxis associated with asthma.
    For bronchospasm associated with asthma in pediatric patients.
    Inhalation dosage (nebulizer solution for inhalation)
    Children and Adolescents 12 to 17 years

    0.63 mg inhaled via nebulization 3 times daily (every 6 to 8 hours) as needed (Max: 1.25 mg/dose). For acute asthma exacerbations, the National Asthma Education and Prevention Program (NAEPP) Expert Panel recommends 1.25 to 2.5 mg via nebulizer every 20 minutes for 3 doses, then 1.25 to 5 mg every 1 to 4 hours as needed. The Global Initiative for Asthma (GINA) guidelines recommend continuous nebulization of a short-acting beta agonist (e.g., albuterol), followed by intermittent as-needed therapy for hospitalized patients 6 years and older (dose not specified); however, GINA emphasizes delivery via a metered dose inhaler with a spacer is most effective and efficient for mild to moderate exacerbations.

    Children 6 to 11 years

    0.31 mg inhaled via nebulization 3 times daily as needed (Max: 0.63 mg/dose). For acute asthma exacerbations, the National Asthma Education and Prevention Program (NAEPP) Expert Panel recommends 0.075 mg/kg/dose (Min: 1.25 mg/dose) via nebulizer every 20 minutes for 3 doses, then 0.075 to 0.15 mg/kg/dose (Max: 5 mg/dose) every 1 to 4 hours as needed. The Global Initiative for Asthma (GINA) guidelines recommend continuous nebulization of a short-acting beta agonist (e.g., albuterol), followed by intermittent as-needed therapy for hospitalized patients 6 years and older (dose not specified); however, GINA emphasizes delivery via a metered dose inhaler with a spacer is most effective and efficient for mild to moderate exacerbations.

    Children 5 years†

    0.31 to 0.63 mg/dose inhaled via nebulization every 8 hours as needed for symptoms of bronchospasm is recommended by the National Asthma Education and Prevention Program (NAEPP) Expert Panel. For acute asthma exacerbations, the NAEPP recommends 0.075 mg/kg/dose (Min: 1.25 mg/dose) via nebulizer every 20 minutes for 3 doses, then 0.075 to 0.15 mg/kg/dose (Max: 5 mg/dose) every 1 to 4 hours as needed. The Global Initiative for Asthma (GINA) guidelines recommend a racemic albuterol dose equivalent to levalbuterol 1.25 mg/dose via nebulization with mouthpiece every 20 minutes for the first hour for acute exacerbations, with reassessment thereafter (further dosing not specified).

    Infants† and Children 4 years and younger†

    0.31 to 1.25 mg/dose inhaled via nebulization every 4 to 6 hours as needed for symptoms of bronchospasm is recommended by the National Asthma Education and Prevention Program (NAEPP) Expert Panel. For acute asthma exacerbations, the NAEPP recommends 0.075 mg/kg/dose (Min: 1.25 mg/dose) inhaled every 20 minutes for 3 doses, then 0.075 to 0.15 mg/kg/dose (Max: 5 mg/dose) every 1 to 4 hours as needed. The Global Initiative For Asthma (GINA) guidelines recommend a racemic albuterol dose equivalent to levalbuterol 1.25 mg/dose via nebulization with mouthpiece (and facemask in those younger than 4 years) every 20 minutes for the first hour for acute exacerbations, with reassessment thereafter (further dosing not specified).

    Oral inhalation dosage (metered-dose inhaler [MDI], e.g., Xopenex HFA)
    Adolescents

    2 puffs every 4 to 6 hours as needed for bronchospasm. In some patients, 1 puff every 4 hours may be sufficient. For acute asthma exacerbations, the National Asthma Education and Prevention Program (NAEPP) Expert Panel recommends 4 to 8 puffs every 20 minutes for up to 4 hours, then 4 to 8 puffs every 1 to 4 hours as needed. The Global Initiative for Asthma (GINA) guidelines recommend up to 4 to 10 puffs administered with a spacer every 20 minutes for the first hour for mild to moderate exacerbations. After the first hour, the dose required may vary from 4 to 10 puffs every 3 to 4 hours up to 6 to 10 puffs every 1 to 2 hours, or more often.

    Children 6 to 12 years

    2 puffs every 4 to 6 hours as needed for bronchospasm. In some patients, 1 puff every 4 hours may be sufficient. For acute asthma exacerbations, the National Asthma Education and Prevention Program (NAEPP) Expert Panel recommends 4 to 8 puffs using a valved holding chamber (VHC) every 20 minutes for 3 doses, then 4 to 8 puffs every 1 to 4 hours as needed. The Global Initiative for Asthma (GINA) guidelines recommend up to 4 to 10 puffs every 20 minutes for the first hour for mild to moderate exacerbations. After the first hour, the dose required may vary from 4 to 10 puffs every 3 to 4 hours up to 6 to 10 puffs every 1 to 2 hours, or more often.

    Children 4 to 5 years

    2 puffs every 4 to 6 hours as needed for bronchospasm. In some patients, 1 puff every 4 hours may be sufficient. For acute asthma exacerbations, the National Asthma Education and Prevention Program (NAEPP) Expert Panel recommends 4 to 8 puffs using a valved holding chamber (VHC) with mouthpiece and/or face mask every 20 minutes for 3 doses, then 4 to 8 puffs every 1 to 4 hours as needed. The Global Initiative for Asthma (GINA) guidelines recommend 2 to 6 puffs every 20 minutes for the first hour, then 2 to 3 puffs every hour as needed for acute exacerbations. GINA recommends transfer to an acute care setting if there is no response to inhaled SABA within 1 to 2 hours or if more than 6 puffs are required during the first 2 hours; if more than 10 puffs are required in 3 to 4 hours, hospital admission is recommended.

    Infants† and Children younger than 4 years†

    Safety and efficacy have not been established as a quick-relief medication for periodic bronchospasm. For acute asthma exacerbations, the National Asthma Education and Prevention Program (NAEPP) Expert Panel recommends 4 to 8 puffs using a valved holding chamber (VHC) and face mask every 20 minutes for 3 doses, then 4 to 8 puffs every 1 to 4 hours as needed. The Global Initiative for Asthma (GINA) guidelines recommend 2 to 6 puffs every 20 minutes for the first hour, then 2 to 3 puffs every hour as needed for acute exacerbations. GINA recommends transfer to an acute care setting if there is no response to inhaled SABA within 1 to 2 hours or if more than 6 puffs are required during the first 2 hours; if more than 10 puffs are required in 3 to 4 hours, hospital admission is recommended.

    For bronchospasm associated with asthma in adults.
    Inhalation dosage (nebulizer solution for inhalation)
    Adults

    0.63 mg inhaled via nebulization 3 times per day, given every 6 to 8 hours, as needed for bronchospasm. Patients with more severe asthma or patients who do not respond adequately may benefit from a dosage of 1.25 mg by nebulization 3 times per day. For acute asthma exacerbations, the National Asthma Education and Prevention Program Expert Panel recommends 1.25 to 2.5 mg every 20 minutes for 3 doses, then 1.25 to 5 mg every 1 to 4 hours as needed. Initiate dosage at the lower end of the range for geriatric patients; if clinically indicated, the dosage may be increased as tolerated, up to the maximum adult dosage. Patients receiving the higher dose should be monitored closely for adverse systemic effects, and the risks of such effects should be balanced against the potential for improved efficacy.

    Oral inhalation dosage (metered-dose inhaler [MDI], e.g., Xopenex HFA)
    Adults

    2 puffs (90 mcg) every 4 to 6 hours as needed for bronchospasm; in some patients, 1 puff (45 mcg) every 4 hours may be sufficient. More frequent administration or a larger number of inhalations is not routinely recommended. For acute asthma exacerbations, the National Asthma Education and Prevention Program (NAEPP) Expert Panel recommends 4 to 8 puffs every 20 minutes for up to 4 hours, then decrease to every 1 to 4 hours as needed.

    For the treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.
    Inhalation dosage (nebulizer solution for inhalation)
    Adults

    Initially, 0.63 mg inhaled by nebulization 3 times per day, given every 6 to 8 hours. Patients who do not respond adequately may benefit from a dosage of 1.25 mg inhaled by nebulization 3 times per day.[51793] According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for COPD, levalbuterol may be used as first-line therapy in Group A and may also be used in Groups B, C, and D for additional symptom control. Short-acting beta-2 agonists (SABAs) such as levalbuterol are preferred therapy for the treatment of acute COPD exacerbations, used with or without a short-acting anticholinergic. The optimal dosage of levalbuterol for the treatment of a COPD exacerbation is not established; adjust dose according to clinical symptoms or the development of adverse effects.[55976] No significant differences in FEV-1 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 patients that are more acutely ill.[63765]

    Oral inhalation dosage (metered-dose inhaler [MDI], e.g., Xopenex HFA)
    Adults

    2 puffs (90 mcg) every 4 to 6 hours; in some patients, 1 puff (45 mcg) every 4 hours may be sufficient. More frequent administration or a larger number of inhalations is not routinely recommended. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for COPD, levalbuterol may be used as first-line therapy in Group A and may also be used in Groups B, C, and D for additional symptom control. Short-acting beta-2 agonists (SABAs) such as levalbuterol are preferred therapy for the treatment of acute COPD exacerbations, used with or without a short-acting anticholinergic. The optimal dosage of levalbuterol for the treatment of an acute COPD exacerbation is not established; adjust dose according to clinical symptoms or the development of adverse effects. No significant differences in FEV-1 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 patients that are more acutely ill.

    For the adjunctive emergency acute treatment of hyperkalemia† until hemodialysis is available.
    NOTE: Beta-agonists can be effective treatments for hyperkalemia via beta-adrenergic induction of potassium (K+) uptake. However, they are a temporary adjunctive measure.
    Oral inhalation dosage (levalbuterol nebulizer solution)
    Adults†

    Single doses of levalbuterol 2.5 mg have been administered in one trial of healthy adults and are reportedly as effective as albuterol 10 mg nebulized. K+ concentrations usually fall within 30 minutes of treatment. Levalbuterol reportedly results in fewer reported side effects than albuterol; however, it is more costly.

    For exercise-induced bronchospasm prophylaxis†.
    Oral inhalation dosage (metered-dose inhaler [MDI], e.g., Xopenex HFA))
    Adults

    2 inhalations (90 mcg) administered 15 minutes before exercise. The American Thoracic Society strongly recommends administration of an inhaled short-acting beta-2 agonist (SABA) 15 minutes before exercise for prevention. The efficacy of levalbuterol for prevention of EIB was assessed in a randomized, double-blind, placebo-controlled, cross over study in 15 asthmatic adults with stable asthma and EIB. Patients were required to have a 20—50% decrease in FEV1 following an exercise challenge and a dose of placebo metered dose inhaler. Low or moderate dose leukotriene inhibitors and inhaled corticosteroids were allowed if the patient was stable on the drug 30 days prior to entry; montelukast, inhaled steroids, and antihistamines were used in 6.7%, 33.3%, and 13.3% of patients, respectively. The primary endpoint was the maximum percent decrease in FEV1 from baseline (post-dose/pre-challenge FEV1). The study consisted of 3 visits; baseline values and EIB diagnosis was confirmed during visit 1, randomization occurred at visit 2 followed by exercise, and patients were crossed over to the opposite treatment at visit 3, followed by exercise. The maximum percent FEV1 decrease was significantly less when patients received levalbuterol compared to placebo (least square mean +/- SE -4.8% +/- 2.8% vs. -22.5% +/- 2.8%, p = 0.0002). Following exercise challenge with levalbuterol prophylaxis, no patients required rescue medication, while 3 patients required rescue medication following placebo prophylaxis.

    Children and Adolescents 4 years and older

    2 puffs inhaled approximately 15 minutes (range, 5 to 20 minutes) before exercise. Protection usually lasts for 2 to 4 hours for most patients. For those who use a short-acting beta-agonist on a daily basis, a controller agent (e.g., inhaled corticosteroid, leukotriene receptor antagonist) should be considered if tolerance develops.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    2 puffs (MDI) every 4 hours as needed for treatment/prevention of bronchospasm; higher doses may be required acutely during severe exacerbations. For nebulized solution, 1.25 mg/dose given 3 times/day for treatment/prevention of bronchospasm.

    Geriatric

    2 puffs (MDI) every 4 hours as needed for treatment/prevention of bronchospasm; higher doses may be required acutely during severe exacerbations. For nebulized solution, 1.25 mg/dose given 3 times/day for treatment/prevention of bronchospasm.

    Adolescents

    2 puffs (MDI) every 4 hours as needed for treatment/prevention of bronchospasm; higher doses may be required acutely during severe asthma exacerbations. For nebulized solution, 1.25 mg/dose given 3 times/day for treatment/prevention of bronchospasm; doses up to 5 mg/dose have been used off-label for acute exacerbations.

    Children

    12 years: 2 puffs (MDI) every 4 hours as needed for treatment/prevention of bronchospasm; higher doses may be required acutely during severe asthma exacerbations. For nebulized solution, 1.25 mg/dose given 3 times/day for treatment/prevention of bronchospasm; doses up to 5 mg/dose have been used off-label for acute exacerbations.
    6 to 11 years: 2 puffs (MDI) every 4 hours as needed for treatment/prevention of bronchospasm; higher doses may be required acutely during severe asthma exacerbations. For nebulized solution, 0.63 mg/dose given 3 times/day for treatment/prevention of bronchospasm; doses up to 0.15 mg/kg/dose (Max: 5 mg/dose) have been used off-label for acute exacerbations.
    4 to 5 years: 2 puffs (MDI) every 4 hours as needed for treatment/prevention of bronchospasm; higher doses may be required acutely during severe asthma exacerbations. Safety and efficacy of the nebulized oral solution has not been established; however, doses up to 0.15 mg/kg/dose (Max: 5 mg/dose) have been used off-label for acute exacerbations.
    Less than 4 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustments are needed.

    Renal Impairment

    No specific dosage adjustments are recommended; caution may be warranted during the administration of high doses in patients with renal impairment, as renal clearance is reduced.

    ADMINISTRATION

    Inhalation Administration
    Oral Inhalation Administration

    Solution for nebulization:
    For 3 mL inhalation solution vials: No dilution is necessary; the single-dose vials are ready-to-use. Use vials immediately after removing from the foil pouch. If the vial is removed from the pouch and then not used immediately, protect from light and use within 1 week. Once protective foil pouch is opened use all contained vials within 2 weeks.[51793]
    For 0.5 mL inhalation solution concentrate vials: Squeeze entire contents of vial into nebulizer reservoir; then, dilute with 2.5 mL of sterile normal saline for inhalation, and gently swirl nebulizer reservoir to mix. If dispensed for home use, instruct patient or caregiver on dilution technique or consider dispensing ready-to-use vials. Use vial immediately after opening individually foil pouched vials.[42050]
    Discard and do not use any vial if the contained solution is not colorless.[42050] [51793]
    The compatibility of levalbuterol inhalation solution with other drugs administered by nebulization has not been established.
    For doses less than 1.25 mg, the 3 mL inhalation solution vials must be used.
    Deliver solution by nebulization over 5 to 15 minutes.
    Safety and efficacy have been established when administered via PARI LC Jet or PARI LC Plus nebulizers and via PARI Master Dura-Neb 2000 or Dura-Neb 3000 compressors.
    The choice of using a mouthpiece versus a face mask must be made based on the skills and understanding of each 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.[42050] [51793]
     
    Aerosol inhalation (metered-dose inhaler [MDI]):
    Instruct patient on proper inhalation technique. Make sure the canister is firmly seated in the plastic mouthpiece adapter before each use. Shake the inhaler well. Prime the inhaler before the initial use by releasing 4 sprays into the air, away from the eyes and face. If not used for more than 3 days, re-prime the inhaler.[51022]
    For patients of any age unable to coordinate inhalation and actuation, a spacer or valved holding chamber (VHC) should be used.
    The choice of using a mouthpiece versus a face mask with a spacer/VHC device must be made based on the skills and understanding of each patient. However, in general, children younger than 4 years require administration with a tight-fitting face mask and spacer/VHC device to achieve optimal delivery. If a face mask is used, allow 5 to 6 inhalations per actuation. Administer 1 puff at a time.[51837]
    If the patient is using other inhalers, instruct them to use levalbuterol first and wait 5 minutes, then use other inhalers as directed.
    Following administration, instruct patient to rinse mouth with water to minimize dry mouth.
    To avoid the spread of infection, do not use the inhaler for more than 1 person.
    The dose indicator on the canister indicates the number of remaining inhalations. The dose indication display will move every tenth actuation. Towards the end of the usable inhalations, the color behind the number in the dose indicator window will change to red. Discard when the dose indicator display window shows "0".
    Clean the plastic mouthpiece of the inhaler at least once a week. After removing the medication canister wash the mouthpiece in warm running water. Shake excess water from the mouthpiece. Allow the actuator to air-dry completely. Blockage from medicine build-up is more likely to occur if the actuator is not allowed to air-dry thoroughly. If build-up occurs, then washing the actuator will remove the blockage.
    The blue actuator (mouthpiece) supplied with levalbuterol (Xopenex HFA) should not be used with any other product canisters; conversely, actuators from other products should not be used with the levalbuterol (Xopenex HFA) canister.[51022]

    STORAGE

    Xopenex:
    - After opening the foil pouch, product should be used within 2 weeks
    - After removing from pouch, protect from light and use product within one week
    - Avoid excessive heat (above 104 degrees F)
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store unused product in foil pouch
    Xopenex Pediatric:
    - After opening the foil pouch, product should be used within 2 weeks
    - After removing from pouch, protect from light and use product within one week
    - Avoid excessive heat (above 104 degrees F)
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store unused product in foil pouch

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Do not exceed the recommended dose of levalbuterol; fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma. The exact cause of death is unknown; however, cardiac arrest following an unexpected development of a severe acute asthmatic crisis and subsequent hypoxia is suspected.

    Albuterol hypersensitivity, angioedema, levalbuterol hypersensitivity

    Levalbuterol is contraindicated in patients with a known levalbuterol hypersensitivity or albuterol hypersensitivity, or hypersensitivity to any component of the specific dosage formulation. Immediate hypersensitivity reactions may occur after administration of racemic albuterol, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema. Like other inhaled beta-agonists, levalbuterol inhalational solution can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, levalbuterol inhalational solution should be discontinued immediately and alternative therapy instituted. It should be recognized that paradoxical bronchospasm, when associated with inhaled formulations, frequently occurs with the first use of a new canister or vial.

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

    Levalbuterol should be used with caution in patients with cardiovascular disorders including ischemic cardiac disease (coronary artery disease), hypertension, cardiac arrhythmias, tachycardia, or QT prolongation. Beta-agonists should also be avoided in patients with suspected or known congenital long QT syndrome due to the risk for torsade de pointes. Use levalbuterol with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, 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 impairment, malnutrition, alcoholism, or hepatic disease may also be at increased risk for QT prolongation. Significant changes in systolic and diastolic blood pressures and heart rate could be expected to occur in some patients after use of any beta-adrenergic bronchodilator. As with other beta-adrenergic agonist medications, levalbuterol may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease is usually transient, not requiring supplementation. Correct pre-existing hypokalemia prior to beta-agonist administration.

    Renal failure, renal impairment

    A study of 5 patients with creatinine clearances ranging from 7 to 53 mL/minute showed that the renal clearance of levalbuterol was reduced by 67%, although the half-life of the drug was not affected. Since levalbuterol is substantially excreted by the kidney, the risk of toxic reactions may be greater in patients with renal impairment including renal failure. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

    Hyperthyroidism, pheochromocytoma, seizure disorder, seizures, thyroid disease, thyrotoxicosis

    Levalbuterol also should be used cautiously in patients with hyperthyroidism (thyrotoxicosis, thyroid disease), pheochromocytoma, unusual responsiveness to other sympathomimetic amines, or a seizure disorder (history of seizures).

    Diabetes mellitus

    Levalbuterol should be used with caution in patients with diabetes mellitus. Large doses of intravenous racemic albuterol have been reported to aggravate preexisting diabetes mellitus and ketoacidosis.

    Deterioration of asthma, paradoxical bronchospasm

    Paradoxical bronchospasm can occur after treatment with levalbuterol and can be life-threatening. If this occurs, levalbuterol should be discontinued immediately and supportive care provided as necessary. Additionally, increased levalbuterol use may indicate asthma destabilization. Asthma may deteriorate acutely over a period of hours or chronically over several days or weeks. If deterioration of asthma occurs during therapy with levalbuterol, appropriate evaluation of the patient and the treatment strategy is warranted, giving special consideration to corticosteroid therapy. Levalbuterol has no anti-inflammatory activity and is not a substitute for inhaled or oral corticosteroid therapy. The use of beta-agonists alone may not be adequate to control asthma in many patients. Early consideration should be given to adding anti-inflammatory agents (e.g., corticosteroids) to the therapeutic regimen. Corticosteroids should not be stopped or reduced when levalbuterol therapy is instituted.

    Labor, obstetric delivery, pregnancy

    Pregnant women receiving levalbuterol should be closely monitored and medications adjusted as necessary to maintain optimal control. There are no adequate and well-controlled studies of levalbuterol during human pregnancy.[51022] Poorly controlled or moderately controlled asthma may present risks to pregnant women and to the fetus; there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate.[51022] During postmarketing experience, various congenital anomalies, including cleft palate and limb defects, have been rarely reported in the infants of patients treated with racemic albuterol. Some of the mothers were taking multiple medications during their pregnancies. No consistent pattern of defects can be discerned, and a relationship between racemic albuterol and congenital anomalies has not been established.[51793] The National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group include short-acting inhaled beta-2 agonists (SABAs) as first-line therapy for mild intermittent asthma during pregnancy, if treatment is required. Albuterol is preferred over other SABAs due to extensive safety-related information during pregnancy. However, there is no evidence of fetal injury with the use of other SABAs, and maintaining a previously established treatment regimen may be more beneficial to the patient.[31822] Due to the potential for beta-agonist interference with uterine contractility, the use of levalbuterol for acute relief of bronchospasm during labor and obstetric delivery should be restricted to those patients in whom the benefits clearly outweigh the risks. Levalbuterol is not approved for the management of pre-term labor; serious adverse events, including pulmonary edema, have been reported after treatment of premature labor with beta-2 agonists.[51022] A pregnancy registry is available to monitor pregnancy outcomes in women exposed to asthma medications, including levalbuterol. To enroll in MotherToBaby Pregnancy Studies' Asthma and Pregnancy Study, patients should call 1-877-311-8972 or visit www.mothertobaby.org/ongoing-study/asthma. 

    Breast-feeding

    There are no available data on the presence of levalbuterol in human milk, the effects on the breast-fed infant, or the effects on milk production. According to the National Asthma Education and Prevention Program (NAEPP) working group for managing asthma during pregnancy, there is no contraindication for use of short-acting inhaled beta-2 agonists (SABAs) during breast-feeding. Plasma concentrations of levalbuterol after inhalation of therapeutic doses are very low in humans, but it is not known whether levalbuterol is excreted in human milk. Gastrointestinal absorption is likely low in the breastfed infant.

    Children, infants, neonates

    Safety and efficacy have not been established for neonates, infants, and children < 4 years for the aerosolized levalbuterol inhaler. Safety and efficacy have also not been established for neonates, infants and children < 6 years with the use of the nebulized levalbuterol product. Clinical trials of levalbuterol nebulized solution (n = 379; children < 6 years) and inhalation aerosol (n = 65; children < 4 years) failed to meet the primary efficacy endpoint and demonstrated an increased number of asthma-related adverse reactions with chronic treatment.

    MAOI therapy

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

    Geriatric

    Clinical trials with levalbuterol nebulizer solution and inhalation aerosol did not include sufficient numbers of geriatric patients to determine if they respond differently than younger adults. general, patients 65 years of age and older should be started at lower doses (e.g., a dose of 0.63 mgper nebulizer dose). If clinically warranted due to insufficient bronchodilator response, the dose may be increased in elderly patients as tolerated, in conjunction with frequent clinical and laboratory monitoring, to the maximum recommended daily adult dose. Since levalbuterol is substantially excreted by the kidney, the risk of toxic reactions may be greater in patients with renal impairment, including geriatric patients with an age-related decline in renal function. It may be useful to monitor renal function. Geriatric patients may be more sensitive to the side effects of beta-agonists, especially tremor and tachycardia. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). The OBRA guidelines caution that inhaled beta-agonists, such as levalbuterol, can cause restlessness, increased heart rate, and anxiety.

    ADVERSE REACTIONS

    Severe

    atrial fibrillation / Early / 0-1.0
    bronchospasm / Rapid / Incidence not known
    arrhythmia exacerbation / Early / Incidence not known

    Moderate

    lymphadenopathy / Delayed / 0-3.0
    sinus tachycardia / Rapid / 2.7-2.8
    migraine / Early / 2.7-2.7
    wheezing / Rapid / 0-2.0
    hypotension / Rapid / 0-2.0
    hypertension / Early / 0-2.0
    chest pain (unspecified) / Early / 0-2.0
    conjunctivitis / Delayed / 0-2.0
    hyperesthesia / Delayed / 0-2.0
    constipation / Delayed / 0-2.0
    hematuria / Delayed / 0-2.0
    candidiasis / Delayed / 0-2.0
    dysphonia / Delayed / Incidence not known
    hypokalemia / Delayed / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    metabolic acidosis / Delayed / Incidence not known

    Mild

    headache / Early / 7.6-11.9
    vomiting / Early / 11.0-11.0
    pharyngitis / Delayed / 3.0-10.4
    fever / Early / 3.0-9.1
    tremor / Early / 6.8-6.8
    diarrhea / Early / 1.5-6.0
    cough / Delayed / 1.4-4.0
    dizziness / Early / 1.4-3.0
    asthenia / Delayed / 3.0-3.0
    sinusitis / Delayed / 1.4-2.7
    dyspepsia / Early / 1.4-2.7
    muscle cramps / Delayed / 0-2.7
    epistaxis / Delayed / 0-2.0
    syncope / Early / 0-2.0
    ocular pruritus / Rapid / 0-2.0
    acne vulgaris / Delayed / 0-2.0
    anxiety / Delayed / 0-2.0
    paresthesias / Delayed / 0-2.0
    insomnia / Early / 0-2.0
    nausea / Early / 0-2.0
    xerostomia / Early / 0-2.0
    myalgia / Early / 1.5-2.0
    dysmenorrhea / Delayed / 0-2.0
    chills / Rapid / 0-2.0
    abdominal pain / Early / 1.5-1.5
    vertigo / Early / Incidence not known
    infection / Delayed / Incidence not known
    gastroesophageal reflux / 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) Sensitive patients may wish to limit or avoid excessive caffeine intake from foods, beverages, dietary supplements and medications during therapy with beta-agonists. Additive side effects may occur between caffeine and beta-agonists. Caffeine is a CNS-stimulant and beta-agonists are sympathomimetic agents. Sensitive patients might experience tremor, sleep difficulties, or mild increases in heart rate.
    Acetaminophen; Butalbital; Caffeine: (Moderate) Sensitive patients may wish to limit or avoid excessive caffeine intake from foods, beverages, dietary supplements and medications during therapy with beta-agonists. Additive side effects may occur between caffeine and beta-agonists. Caffeine is a CNS-stimulant and beta-agonists are sympathomimetic agents. Sensitive patients might experience tremor, sleep difficulties, or mild increases in heart rate.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Sensitive patients may wish to limit or avoid excessive caffeine intake from foods, beverages, dietary supplements and medications during therapy with beta-agonists. Additive side effects may occur between caffeine and beta-agonists. Caffeine is a CNS-stimulant and beta-agonists are sympathomimetic agents. Sensitive patients might experience tremor, sleep difficulties, or mild increases in heart rate.
    Acetaminophen; Caffeine: (Moderate) Sensitive patients may wish to limit or avoid excessive caffeine intake from foods, beverages, dietary supplements and medications during therapy with beta-agonists. Additive side effects may occur between caffeine and beta-agonists. Caffeine is a CNS-stimulant and beta-agonists are sympathomimetic agents. Sensitive patients might experience tremor, sleep difficulties, or mild increases in heart rate.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Sensitive patients may wish to limit or avoid excessive caffeine intake from foods, beverages, dietary supplements and medications during therapy with beta-agonists. Additive side effects may occur between caffeine and beta-agonists. Caffeine is a CNS-stimulant and beta-agonists are sympathomimetic agents. Sensitive patients might experience tremor, sleep difficulties, or mild increases in heart rate.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Sensitive patients may wish to limit or avoid excessive caffeine intake from foods, beverages, dietary supplements and medications during therapy with beta-agonists. Additive side effects may occur between caffeine and beta-agonists. Caffeine is a CNS-stimulant and beta-agonists are sympathomimetic agents. Sensitive patients might experience tremor, sleep difficulties, or mild increases in heart rate.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Sensitive patients may wish to limit or avoid excessive caffeine intake from foods, beverages, dietary supplements and medications during therapy with beta-agonists. Additive side effects may occur between caffeine and beta-agonists. Caffeine is a CNS-stimulant and beta-agonists are sympathomimetic agents. Sensitive patients might experience tremor, sleep difficulties, or mild increases in heart rate.
    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.
    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 beta-agonists due to the potential for QT prolongation. Alfuzosin may prolong the QT interval in a dose-dependent manner. 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.
    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. The concomitant use of amiodarone and other drugs known to prolong the QT interval, such as beta-agonists, should only be done after careful assessment of risks versus benefits. Beta-agonists may rarely be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    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 used cautiously and with close monitoring with anagrelide. 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 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.
    Apomorphine: (Minor) Beta-agonists should be used cautiously and with close monitoring with apomorphine. Limited data indicate that QT prolongation is possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines. In one study, a single mean dose of 5.2 mg (range 2 to10 mg) prolonged the QT interval by about 3 msec. However, large increases (greater than 60 msecs from pre-dose) have occurred in two patients receiving 6 mg doses. Doses less than or equal to 6 mg SC are associated with minimal increases in QTc; doses greater than 6 mg SC do not provide additional clinical benefit and are not recommended. 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.
    Aripiprazole: (Minor) QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Caution advised if administering with other drugs that may cause QT prolongation and torsade de pointes (TdP), including the beta-agonists. Beta-agonists may 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) Sensitive patients may wish to limit or avoid excessive caffeine intake from foods, beverages, dietary supplements and medications during therapy with beta-agonists. Additive side effects may occur between caffeine and beta-agonists. Caffeine is a CNS-stimulant and beta-agonists are sympathomimetic agents. Sensitive patients might experience tremor, sleep difficulties, or mild increases in heart rate.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Sensitive patients may wish to limit or avoid excessive caffeine intake from foods, beverages, dietary supplements and medications during therapy with beta-agonists. Additive side effects may occur between caffeine and beta-agonists. Caffeine is a CNS-stimulant and beta-agonists are sympathomimetic agents. Sensitive patients might experience tremor, sleep difficulties, or mild increases in heart rate.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Sensitive patients may wish to limit or avoid excessive caffeine intake from foods, beverages, dietary supplements and medications during therapy with beta-agonists. Additive side effects may occur between caffeine and beta-agonists. Caffeine is a CNS-stimulant and beta-agonists are sympathomimetic agents. Sensitive patients might experience tremor, sleep difficulties, or mild increases in heart rate.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Sensitive patients may wish to limit or avoid excessive caffeine intake from foods, beverages, dietary supplements and medications during therapy with beta-agonists. Additive side effects may occur between caffeine and beta-agonists. Caffeine is a CNS-stimulant and beta-agonists are sympathomimetic agents. Sensitive patients might experience tremor, sleep difficulties, or mild increases in heart rate.
    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.
    Azithromycin: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and short-acting beta-agonists should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. 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.
    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.
    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.
    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) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with metronidazole include beta-agonists.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with metronidazole include 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.
    Bretylium: (Minor) The use of bretylium (a class III antiarrhythmic agent) in conjunction with other drugs associated with QT prolongation should be used with caution due to the potential risk for ventricular tachycardia, including torsade de pointes. Agents associated with a low, but possible risk for QT prolongation and TdP based on varying levels of documentation 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.
    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; 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.
    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.
    Caffeine: (Moderate) Sensitive patients may wish to limit or avoid excessive caffeine intake from foods, beverages, dietary supplements and medications during therapy with beta-agonists. Additive side effects may occur between caffeine and beta-agonists. Caffeine is a CNS-stimulant and beta-agonists are sympathomimetic agents. Sensitive patients might experience tremor, sleep difficulties, or mild increases in heart rate.
    Caffeine; Ergotamine: (Moderate) Sensitive patients may wish to limit or avoid excessive caffeine intake from foods, beverages, dietary supplements and medications during therapy with beta-agonists. Additive side effects may occur between caffeine and beta-agonists. Caffeine is a CNS-stimulant and beta-agonists are sympathomimetic agents. Sensitive patients might experience tremor, sleep difficulties, or mild increases in heart rate.
    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.
    Chloroquine: (Minor) Beta-agonists should be used cautiously and with close monitoring with chloroquine. Chloroquine administration is associated with an increased risk of QT prolongation and torsades de pointes (TdP). The need to coadminister chloroquine with drugs known to prolong the QT interval should be done with a careful assessment of risks versus benefits and should be avoided when possible. 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.
    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: (Severe) 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) For patients taking a deutetrabenazine dosage more than 24 mg/day with a short-acting beta-agonist, assess the QTc interval before and after increasing the dosage of either medication. Clinically relevant QTc prolongation may occur with deutetrabenazine. 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.
    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.
    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: (Severe) 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.
    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.
    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.
    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.
    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: (Severe) 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.
    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: (Minor) Use caution with coadministration of hydroxychloroquine and short-acting beta-agonists. Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes have been reported with the use of hydroxychloroquine. 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.
    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.
    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 co-use, 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. At least one case of hypertension occurred in a patient with previous episodes of high blood pressure who was receiving albuterol and selegiline concurrently. 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: (Severe) 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.
    Lomefloxacin: (Minor) Some quinolones, including lomefloxacin, have been associated with QT prolongation and infrequent cases of arrhythmia. Post-marketing surveillance for lomefloxacin has identified very rare cases of torsade de pointes (TdP). Other medications which might prolong the QT interval should be used cautiously when given concurrently with lomefloxacin 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.
    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: (Minor) QT prolongation in patients taking lopinavir; ritonavir has been reported. Coadministration with other drugs that prolong the QT interval may result in additive QT prolongation. Use cautiously with drugs that 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. Concomitant use of salmeterol and lopinavir; ritonavir is not recommended as increased concentrations of salmeterol may occur via inhibition of CYP3A4, which might increase the risk for cardiac adverse reactions, like increased heart rate.
    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.
    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: (Severe) 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 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.
    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) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with metronidazole include 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 co-use, 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. At least one case of hypertension occurred in a patient with previous episodes of high blood pressure who was receiving albuterol and selegiline concurrently. 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.
    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) 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. 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. 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.
    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 co-use, 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. At least one case of hypertension occurred in a patient with previous episodes of high blood pressure who was receiving albuterol and selegiline concurrently. 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: (Severe) 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.
    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.
    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.
    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.
    Selegiline: (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 co-use, 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. At least one case of hypertension occurred in a patient with previous episodes of high blood pressure who was receiving albuterol and selegiline concurrently. 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.
    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) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of sorafenib with short-acting beta-agonists is necessary; correct any electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Sorafenib 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.
    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: (Severe) 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 co-use, 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. At least one case of hypertension occurred in a patient with previous episodes of high blood pressure who was receiving albuterol and selegiline concurrently. 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.
    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.
    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) Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil produce an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction). The effect of vardenafil on the QT interval should be considered when prescribing the drug. Drugs with a possible risk for QT prolongation that should be used cautiously with vardenafil 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.
    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.
    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 levalbuterol in human milk, the effects on the breast-fed infant, or the effects on milk production. According to the National Asthma Education and Prevention Program (NAEPP) working group for managing asthma during pregnancy, there is no contraindication for use of short-acting inhaled beta-2 agonists (SABAs) during breast-feeding. Plasma concentrations of levalbuterol after inhalation of therapeutic doses are very low in humans, but it is not known whether levalbuterol is excreted in human milk. Gastrointestinal absorption is likely low in the breastfed infant.

    MECHANISM OF ACTION

    Mechanism of Action: Levalbuterol is the R-isomer of albuterol. It is a moderately selective beta2-adrenergic agonist that stimulates receptors of the smooth muscle in the lungs, uterus, and vasculature supplying skeletal muscle. Results from an in vitro study of binding to human beta-adrenergic receptors demonstrated that levalbuterol has approximately 2-fold greater binding affinity than racemic albuterol and approximately 100-fold greater binding affinity than (S)-albuterol. The R-isomer of albuterol, levalbuterol, is primarily responsible for bronchodilation, while the S-isomer lacks significant bronchodilator effects. Although not confirmed during clinical trials in humans, the S-isomer of albuterol has bronchoconstrictive properties in animal models. Data showing an increase in airway reactivity from the administration of S-albuterol are lacking in humans.Intracellularly, the actions of levalbuterol are mediated by cyclic AMP, the production of which is augmented by beta2-stimulation. Levalbuterol is believed to work by activating adenylate cyclase, the enzyme responsible for generating cyclic AMP, an intracellular mediator. Increased cyclic AMP leads to activation of protein kinase A, which inhibits phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in relaxation. The net result of beta2-receptor agonism in the lungs is relaxation of bronchial and tracheal smooth muscles, which in turn relieves bronchospasm, reduces airway resistance, facilitates mucous drainage, and increases vital capacity.Levalbuterol can also inhibit the degranulation and subsequent release of inflammatory autocoids from mast cells. Stimulation of beta2-receptors on peripheral vascular smooth muscle can cause vasodilation and a modest decrease in diastolic blood pressure. Beta2-adrenergic stimulation also results in intracellular accumulation of serum potassium, possibly due to stimulation of the Na/K ATPase pump, leading to moderate degrees of hypokalemia.

    PHARMACOKINETICS

    Levalbuterol is administered via nebulized or aerosolized oral inhalation. Racemic albuterol crosses the blood-brain barrier and may cross the placenta. R-albuterol appears to be preferentially metabolized in the gastrointestinal tract, presumably by SULT1A3 (sulfotransferase). The primary route of elimination of R-albuterol is through renal excretion (80% to 100%), with 25% to 46% being excreted as unchanged drug in the urine. Less than 20% of the drug is excreted in the feces. The half-life is 3.3 to 4 hours in patients 12 years and older.
     
    Affected cytochrome P450 (CYO450) isoenzymes or drug transporters: None

    Inhalation Route

    Following oral inhalation, levalbuterol is absorbed over several hours from the respiratory tract. Most of an inhaled dose is actually swallowed and absorbed through the GI tract. Plasma levels of levalbuterol after oral inhalation of therapeutic doses are very low. Peak serum concentrations of R-albuterol occur in 0.2 hours.
    Oral inhalation solution: The mean onset time (15% increase in FEV-1) for nebulized doses of 0.63 mg and 1.25 mg levalbuterol was approximately 17 and 10 minutes, respectively. The mean time to peak effect is approximately 1.5 hours. The mean duration (more than a 15% increase in FEV-1) following administration of 0.63 and 1.25 mg doses of levalbuterol is 5 and 6 hours, respectively. In some patients, the duration of effect was as long as 8 hours.
    Oral inhalation aerosol: The mean onset time (15% increase in FEV-1) for aerosolized doses of 90 mcg of levalbuterol (2 inhalations) ranges from 4.5 to 10.2 minutes. The mean time to peak effect is 76 to 78 minutes. The mean duration (more than a 15% increase in FEV-1) following administration of 90 mcg of levalbuterol is 3 hours, with a duration of effect as long as 6 hours in some patients.