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  • CLASSES

    B2-stimulants, Oral
    Short-acting B2-stimulants, Inhalant

    DEA CLASS

    Rx

    DESCRIPTION

    Short acting, selective beta-2 agonist
    Used in the management of asthma or COPD; also used to prevent exercise-induced bronchospasm
    Known as salbutamol outside of the US

    COMMON BRAND NAMES

    Accuneb, Proair HFA, ProAir RespiClick, Proventil, Proventil HFA, Proventil Repetabs, Respirol, Ventolin, Ventolin HFA, Volmax, VoSpire ER

    HOW SUPPLIED

    Accuneb/Albuterol/Albuterol Sulfate/Proventil Respiratory (Inhalation) Sol: 0.083%, 0.5%, 0.5mL, 0.63mg, 1.25mg, 2.5mg, 3mL
    Albuterol/Albuterol Sulfate/Proventil Repetabs Oral Tab: 2mg, 4mg
    Albuterol/Albuterol Sulfate/Ventolin Oral Syrup: 2mg, 5mL
    Albuterol/Albuterol Sulfate/Volmax/VoSpire ER Oral Tab ER: 4mg, 8mg
    Albuterol/Proair HFA/Proventil/Proventil HFA/Respirol/Ventolin/Ventolin HFA Respiratory (Inhalation) Aer Met: 1actuation, 90mcg
    ProAir RespiClick Respiratory (Inhalation) Inhalant: 1actuation, 90mcg

    DOSAGE & INDICATIONS

    For the treatment of acute bronchospasm (e.g., asthma) and bronchospasm prophylaxis.
    For bronchospasm associated reversible obstructive airway disease (i.e., asthma).
    Oral inhalation dosage (metered-dose inhaler [MDI])
    Adults

    180 mcg (2 puffs) every 4 to 6 hours as needed. In some patients, 90 mcg (1 puff) every 4 hours may be sufficient. FDA-approved labeling recommends to not exceed 12 puffs/day. For the acute treatment of severe episodes, the National Asthma Education and Prevention Program 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. Short-acting beta-2-agonists are the therapy of choice for the treatment of acute asthma symptoms. For mild to moderate exacerbations, the use of a metered-dose inhaler plus valved holding chamber is as effective as nebulized therapy when appropriate administration technique is used.

    Adolescents

    2 puffs every 4 to 6 hours as needed for bronchospasm. In some patients, 1 puff every 4 hours may be sufficient. FDA-approved labeling recommends to not exceed 12 puffs/day. For the 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. FDA-approved labeling recommends to not exceed 12 puffs/day. For acute asthma exacerbations, the National Asthma Education and Prevention Program (NAEPP) Expert Panel recommends 4 to 8 puffs 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 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 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. FDA-approved labeling recommends to not exceed 12 puffs/day. For acute asthma exacerbations, the National Asthma Education and Prevention Program (NAEPP) Expert Panel recommends 4 to 8 puffs 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 using a valved holding chamber (VHC) with mouthpiece and/or facemask 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†

    2 puffs using a valved holding chamber (VHC) and face mask 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 4 to 8 puffs using a 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. Three clinical trials of albuterol MDIs administered with a VHC and face mask failed to show a significant improvement in asthma symptom scores in infants and children younger than 4 years of age with bronchospasm associated with obstructive airway disease. Of note, safety profiles observed in patients younger than 4 years of age were comparable to those observed in older patients.

    Neonates†

    1 to 2 puffs/dose administered via inspiratory limb of the mechanical ventilator circuit appear to improve pulmonary mechanics in ventilator-dependent neonates. In a survey of 68 academic medical center neonatal intensive care units (NICUs), 95% reported 1 to 2 puffs as the average dose used. Frequency of administration has not been clearly defined in the neonatal population; albuterol administration is recommended every 1 to 4 hours as needed in other pediatric populations. Of note, MDIs with inline spacers have demonstrated superior drug delivery when compared to jet nebulizers in simulated neonatal lung models.

    Oral inhalation dosage (dry-powder inhaler [DPI]; e.g., ProAir RespiClick)
    Adults

    180 mcg (2 oral inhalations) every 4 to 6 hours as needed. In some patients, 90 mcg (1 oral inhalation) every 4 hours may be sufficient. FDA-approved labeling recommends to not exceed 12 inhalations/day. NOTE: Do not use the device with a spacer or volume holding chamber.

    Children and Adolescents 4 years and older

    180 mcg (2 oral inhalations) every 4 to 6 hours as needed. In some patients, 90 mcg (1 oral inhalation) every 4 hours may be sufficient. FDA-approved labeling recommends to not exceed 12 inhalations/day. NOTE: Do not use the device with a spacer or volume holding chamber.

    Oral inhalation dosage (nebulized solution)
    Adults

    2.5 mg via oral inhalation every 6 to 8 hours as needed, delivered over 5 to 15 minutes. FDA-approved labeling recommends to not exceed 4 doses/day. For the acute treatment of severe episodes, 2.5 to 5 mg initially every 20 minutes for 3 doses, then 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hour by continuous nebulization.

    Adolescents

    1.25 to 5 mg via oral inhalation every 4 to 8 hours as needed for bronchospasm is recommended by the National Asthma Education and Prevention Program (NAEPP) Expert panel. For acute asthma exacerbations, NAEPP recommends 2.5 to 5 mg every 20 minutes for 3 doses, then 2.5 to 10 mg every 1 to 4 hours as needed or 10 to 15 mg/hour by continuous nebulization. The Global Initiative for Asthma (GINA) guidelines recommend continuous nebulization, followed by intermittent as-needed therapy for hospitalized adolescents (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. FDA-approved labeling recommends 2.5 mg via oral inhalation 3 to 4 times daily as needed; do not exceed 4 doses/day. Doses should be delivered over 5 to 15 minutes.

    Children 6 to 12 years

    1.25 to 5 mg via oral inhalation every 4 to 8 hours as needed for bronchospasm is recommended by the National Asthma Education and Prevention Program (NAEPP) Expert panel. For acute asthma exacerbations, NAEPP recommends 0.15 mg/kg/dose (Min: 2.5 mg/dose) every 20 minutes for 3 doses, then 0.15 to 0.3 mg/kg/dose (Max: 10 mg/dose) every 1 to 4 hours as needed or 0.5 mg/kg/hour by continuous nebulization. The Global Initiative for Asthma (GINA) guidelines recommend continuous nebulization, 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. FDA-approved labeling for albuterol 0.083% solution recommends 2.5 mg via oral inhalation 3 to 4 times daily as needed; do not exceed 4 doses/day. For the 0.5% solution, the initial dose is 0.1 to 0.15 mg/kg/dose, with subsequent dosing titrated to achieve desired clinical response. Max: 2.5 mg/dose 3 to 4 times daily. Doses should be delivered over 5 to 15 minutes.

    Children 5 years

    1.25 to 5 mg via oral inhalation every 4 to 8 hours as needed for bronchospasm is recommended by the National Asthma Education and Prevention Program (NAEPP) Expert panel. For acute asthma exacerbations, NAEPP recommends 0.15 mg/kg/dose (Min: 2.5 mg/dose) every 20 minutes for 3 doses, then 0.15 to 0.3 mg/kg/dose (Max: 10 mg/dose) every 1 to 4 hours as needed or 0.5 mg/kg/hour by continuous nebulization. The Global Initiative for Asthma (GINA) guidelines recommend 2.5 mg/dose via nebulization with mouthpiece every 20 minutes for the first hour for acute exacerbations, with reassessment thereafter (further dosing not specified). FDA-approved labeling for albuterol 0.083% solution recommends 2.5 mg via oral inhalation 3 to 4 times daily as needed; do not exceed 4 doses/day. For the 0.5% solution, the initial dose is 0.1 to 0.15 mg/kg/dose, with subsequent dosing titrated to achieve desired clinical response. Max: 2.5 mg/dose 3 to 4 times daily. Doses should be delivered over 5 to 15 minutes.

    Children 2 to 4 years

    0.63 to 2.5 mg via oral inhalation 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 0.15 mg/kg/dose (Min: 2.5 mg/dose) via oral inhalation every 20 minutes for 3 doses, then 0.15 to 0.3 mg/kg/dose (Max: 10 mg/dose) every 1 to 4 hours as needed or 0.5 mg/kg/hour by continuous nebulization. The Global Initiative for Asthma (GINA) guidelines recommend 2.5 mg 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). According to FDA-approved labeling, initial dosing for albuterol 0.5% solution is 0.1 to 0.15 mg/kg/dose, with subsequent dosing titrated to achieve desired clinical response. Max: 2.5 mg/dose 3 to 4 times daily; do not exceed 4 doses/day. For patients weighing at least 15 kg, the 0.083% solution may be used at a dose of 2.5 mg via oral inhalation 3 to 4 times daily as needed. Doses should be delivered over 5 to 15 minutes.

    Infants† and Children younger than 2 years†

    0.63 to 2.5 mg via oral inhalation 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 0.15 mg/kg/dose (Min: 2.5 mg/dose) vial oral inhalation every 20 minutes for 3 doses, then 0.15 to 0.3 mg/kg/dose (Max: 10 mg/dose) every 1 to 4 hours as needed or 0.5 mg/kg/hour by continuous nebulization. The Global Initiative for Asthma (GINA) guidelines recommend 2.5 mg via nebulization with face mask every 20 minutes for the first hour for acute exacerbations, with reassessment thereafter (further dosing not specified).

    Neonates†

    1.25 to 2.5 mg via inhalation was the most common nebulized dose reported in a survey of 68 academic medical center neonatal intensive care units (NICUs). While significantly less common, weight-based dosing of 0.05 to 0.1 mg/kg/dose was also reported by some centers as their usual dose. Published reports describe a wide range of effective doses; 0.2 to 5 mg/dose and 0.02 to 0.2 mg/kg/dose administered every 4 to 8 hours have been reported to improve pulmonary compliance and/or resistance in ventilator-dependent neonates. Frequency of administration has not been clearly defined in the neonatal population; albuterol administration is recommended every 1 to 6 hours as needed in other pediatric populations. Of note, significantly larger doses of albuterol are used in nebulization when compared to administration with metered-dose inhalers (MDIs) due to inefficiency of nebulized drug delivery.

    Oral inhalation dosage (Accuneb nebulized solution)
    Children 5 to 12 years

    0.63 to 1.25 mg via oral inhalation 3 to 4 times daily as needed. FDA-approved labeling recommends to not exceed 4 doses/day. Doses should be delivered over 5 to 15 minutes. A higher concentration product (0.083% or 0.5% solution for inhalation) may be more appropriate for treatment of acute exacerbations. In general, the National Asthma Education and Prevention Program (NAEPP) Expert panel recommends albuterol 1.25 to 5 mg via oral inhalation every 4 to 8 hours as needed for bronchospasm.

    Children 2 to 4 years

    0.63 to 1.25 mg via oral inhalation 3 to 4 times daily as needed. FDA-approved labeling recommends to not exceed 4 doses/day. Doses should be delivered over 5 to 15 minutes. A higher concentration product (0.083% or 0.5% solution for inhalation) may be more appropriate for treatment of acute asthma exacerbations. In general, the National Asthma Education and Prevention Program (NAEPP) Expert Panel recommends albuterol 0.63 to 2.5 mg via oral inhalation every 4 to 6 hours as needed for symptoms of bronchospasm.

    Children younger than 2 years†

    0.63 to 2.5 mg via oral inhalation every 4 to 6 hours as needed for symptoms of bronchospasm is recommended by the National Asthma Education and Prevention Program (NAEPP) Expert Panel. The manufacturer of AccuNeb recommends a higher concentration product (0.083% or 0.5% solution for inhalation) for treatment of acute asthma exacerbations.

    Oral dosage (oral syrup)
    Adults

    2 to 4 mg PO every 6 to 8 hours. Geriatric patients should receive 2 mg PO every 6 to 8 hours. Max: 32 mg/day PO. 

    Adolescents 15 years and older

    Initially, 2 to 4 mg PO 3 to 4 times per day. If adequate response not obtained, dose may be increased gradually with caution. Max: 32 mg/day PO.

    Children and Adolescents 6 to 14 years

    Initially, 2 mg PO 3 to 4 times per day. If an adequate response is not obtained, dose may be increased gradually with caution. Max: 24 mg/day PO.

    Children 2 to 5 years

    Initially, 0.1 mg/kg PO every 8 hours (Max: 6 mg/day PO). If an adequate response is not obtained, dose may be gradually increased to 0.2 mg/kg/dose PO every 8 hours (Max: 12 mg/day PO).

    Infants† and Children younger than 2 years†

    Safety and efficacy have not been established. Dosing is not available for this age group; however, 0.1 to 0.2 mg/kg/dose PO every 8 hours has been used in neonates and young children.

    Neonates†

    Limited data. In a randomized, placebo-controlled trial enteral albuterol 0.15 mg/kg/dose every 8 hours for 96 hours improved pulmonary resistance in ventilator dependent premature neonates at risk for developing chronic lung disease (n = 30). Improvement was achieved without major cardiovascular side effects, although patients did experience statistically significant heart and respiratory rate increases deemed clinically unimportant by investigators.

    Oral dosage (immediate-release tablets)
    Adults

    2 to 4 mg PO every 6 to 8 hours. Geriatric patients should receive 2 mg PO every 6 to 8 hours. Max: 32 mg/day PO.

    Adolescents

    Initially, 2 to 4 mg PO 3 to 4 times per day. If an adequate response is not obtained, dose may be increased gradually with caution. Max: 32 mg/day PO.

    Children 6 to 12 years

    Initially, 2 mg PO 3 to 4 times per day. If an adequate response is not obtained, dose may be increased gradually with caution. Max: 24 mg/day PO.

    Oral dosage (extended-release tablets)
    Adults and Adolescents

    Initially, 4 to 8 mg PO every 12 hours. If an adequate response is not obtained, dose may be increased gradually with caution. Max: 32 mg/day PO. DOSE CONVERSION: 2 mg immediate-release PO every 6 hours = 4 mg extended-release PO every 12 hours. In general, inhaled long-acting beta-agonists are preferred since they are longer-acting and have fewer side effects than oral sustained-release agents.

    Children 6 to 12 years

    Initially, 4 mg PO every 12 hours. If an adequate response is not obtained, dose may be increased gradually with caution. Max: 24 mg/day PO. DOSE CONVERSION: 2 mg immediate-release PO every 6 hours = 4 mg extended-release PO every 12 hours. In general, inhaled long-acting beta-agonists are preferred since they are longer-acting and have fewer side effects than oral sustained-release agents.

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

    2 inhalations (180 mcg) at least 15 minutes prior to exercise; many manufacturers recommend giving 15 to 30 minutes prior to exercise. Protection lasts 2 to 3 hours in most patients. Inhaled short-acting beta-2 agonists (SABAs) are the therapy of choice for preventing exercise-induced bronchospasm, and they are strongly recommended by the American Thoracic Society for EIB prophylaxis.

    Children and Adolescents 5 to 17 years

    2 puffs administered 5 to 30 minutes before exercise. Protection may last 2 to 4 hours. 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 albuterol tolerance develops.

    Children 4 years

    1 to 2 puffs administered 5 to 30 minutes before exercise. Protection may last 2 to 4 hours. 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 albuterol tolerance develops.

    Children 1 to 3 years

    1 to 2 puffs administered 5 to 20 minutes before exercise. Protection may last 2 to 4 hours. 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 albuterol tolerance develops.

    Oral inhalation dosage (dry-powder inhaler [DPI]; ProAir RespiClick)
    Adults

    2 oral inhalations (180 mcg) 15 to 30 minutes prior to exercise. The action of albuterol inhalation powder should last for 4 to 6 hours. NOTE: Do not use the device with a spacer or volume holding chamber. Inhaled short-acting beta-2 agonists (SABAs) are the therapy of choice for preventing exercise-induced bronchospasm, and they are strongly recommended by the American Thoracic Society for EIB prophylaxis. 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 albuterol tolerance develops.

    Children and Adolescents 4 years and older

    2 oral inhalations (180 mcg) 15 to 30 minutes prior to exercise. The action of albuterol inhalation powder should last for 4 to 6 hours. NOTE: Do not use the device with a spacer or volume holding chamber. Inhaled short-acting beta-2 agonists (SABAs) are the therapy of choice for preventing exercise-induced bronchospasm, and they are strongly recommended by the American Thoracic Society for EIB prophylaxis. 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 albuterol tolerance develops.

    For the adjunctive emergency acute treatment of hyperkalemia†.
    Oral inhalation dosage (nebulized solution)
    Adults†

    Single doses of 10 to 20 mg have been administered. K+ concentrations begin to fall within 30 minutes of administration, and may remain depressed up to 300 minutes when albuterol is nebulized. Inhaled short acting beta-agonists treat hyperkalemia through beta-adrenergic stimulation of cellular potassium (K+) uptake. However, it is a temporary adjunctive measure. Adjuvant or alternative therapy is warranted for patients experiencing electrocardiographic (ECG) changes or significantly elevated serum potassium concentrations.

    Children and Adolescents weighing 25 kg or more

    5 mg/dose via oral inhalation was effective in a small study of pediatric patients (5 to 18 years of age) with end stage renal failure (n = 11). Doses were repeated every 2 hours as needed. Adjuvant or alternative therapy is warranted for patients experiencing electrocardiographic (ECG) changes or significantly elevated serum potassium concentrations.

    Children weighing less than 25 kg

    2.5 mg/dose via oral inhalation was effective in a small study of pediatric patients (5 to 18 years of age) with end stage renal failure (n = 11). Doses were repeated every 2 hours as needed. Adjuvant or alternative therapy is warranted for patients experiencing electrocardiographic (ECG) changes or significantly elevated serum potassium concentrations.

    Infants

    Although not specifically studied in this population, nebulized albuterol 2.5 mg in children weighing less than 25 kg every 2 hours was effective in pediatric end stage renal failure patients. Smaller doses for younger infants may be necessary. A dose of 400 mcg every 2 hours was effective in lowering serum potassium concentrations to less than 5 mmol/L in mechanically ventilated newborns weighing less than 2,000 grams. Adjuvant or alternative therapy is warranted for patients experiencing electrocardiographic changes or significantly elevated serum potassium concentrations.

    Neonates

    400 mcg via oral inhalation administered every 2 hours was effective in a study of mechanically ventilated neonates weighing less than 2,000 grams (n = 19). Doses were repeated every 2 hours until serum potassium concentrations fell to less than 5 mmol/L, the patient experienced adverse effects, or the maximum of 12 doses was reached. Adjuvant or alternative therapy is warranted for patients experiencing electrocardiographic (ECG) changes or significantly elevated serum potassium concentrations (e.g., more than 7.5 mmol/L).

    For the treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD)† including chronic bronchitis† and emphysema†.
    Oral inhalation dosage (metered-dose inhaler [MDI]; e.g., ProAir HFA)
    Adults

    180 mcg (2 puffs) every 4 to 6 hours as needed for symptoms. In some patients, 90 mcg (1 puff) every 4 hours may be sufficient. FDA-approved labeled maximum: 12 puffs/day. Albuterol may be used as needed for first line therapy for GOLD group A category patients with stable COPD (few symptoms and a low risk of exacerbation). Albuterol may be used routinely or with a short-acting anticholinergic in group A patients who continue to have evidence of bronchospasm with monotherapy, or a long-acting bronchodilator may be introduced; albuterol may also be used in GOLD B, C, and D category patients with stable disease for additional symptom control. Evidence does not support the use of high doses of albuterol on an as needed basis in patients already treated with long-acting bronchodilators. Short-acting-beta-2-agonists such as albuterol are preferred therapy for the treatment of COPD exacerbations, used with or without a short-acting anticholinergic. Increasing the dosage and/or frequency of administration during an exacerbation is recommended for clinical improvement. The optimal dosage of albuterol for the treatment of an acute COPD exacerbation is not established; adjust dose according to clinical symptoms or the development of adverse effects. A regimen of incremental doses using puff aerosol (cumulative doses of 200 mcg, 400 mcg, 800 mcg, 1,600 mcg, and 3,200 mcg) given sequentially every 20 minutes with a spacer, followed by maintenance dosing using nebulized albuterol has been used. No significant differences in FEV1 have been demonstrated between metered-dose inhalers (with or without a spacer) and nebulizers among short-acting bronchodilators in clinical trials; nebulizers may be more convenient for sicker patients.

    Inhalational dosage (nebulizer solution)
    Adults

    2.5 mg inhaled via nebulizer every 6 to 8 hours as needed, delivered over 5 to 15 minutes. FDA-approved labeling recommends to not exceed 4 doses/day. Albuterol may be used as needed for first line therapy for GOLD group A category patients with stable COPD (few symptoms and a low risk of exacerbation). Albuterol may be used routinely or with a short-acting anticholinergic in group A patients who continue to have evidence of bronchospasm with monotherapy, or a long-acting bronchodilator may be introduced; albuterol may also be used in GOLD B, C, and D category patients with stable disease for additional symptom control. Evidence does not support the use of high doses of albuterol on an as needed basis in patients already treated with long-acting bronchodilators. Short-acting beta-2 agonists (SABAs) such as albuterol are preferred therapy for the treatment of acute COPD exacerbations, used with or without a short-acting anticholinergic. Increasing the dosage and/or frequency of administration during an exacerbation is recommended for clinical improvement. The optimal dosage of albuterol for the treatment of an acute COPD exacerbation is not established; adjust dose according to clinical symptoms or the development of adverse effects. A nebulized albuterol dose of 5 mg every 4 hours has been used, as well as a regimen of 2.5 mg given every 20 minutes for 2 hours. No significant differences in FEV1 have been demonstrated between metered-dose inhalers (with or without a spacer) and nebulizer treatments; nebulizers may be more convenient those who are more acutely ill.

    Oral dosage (immediate-release dosage forms)
    Adults

    2 to 4 mg PO every 6 to 8 hours. Geriatric patients should receive 2 mg PO every 6 to 8 hours initially. Maximum: 32 mg/day PO. Inhaled bronchodilators are preferred over oral bronchodilators for the management of COPD.

    Oral dosage (extended-release tablets)
    Adults

    4 to 8 mg PO every 12 hours (Maximum: 32 mg/day PO). Inhaled bronchodilators are preferred over oral bronchodilators for the management of COPD.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    32 mg/day PO for syrup and tablets; FDA-approved labeling for inhaler recommends not exceeding 12 puffs/day; FDA-approved labeling for nebulizer solution for oral inhalation recommends not exceeding 4 doses/day or 10 mg/day (0.083% or 0.5% nebulizer solution), 2.5 mg/day (0.63 mg/3 mL nebulizer solution), and 5 mg/day (1.25 mg/3 mL nebulizer solution). Higher maximum dosages for inhalation products have been recommended in NAEPP guidelines for acute exacerbations of asthma.

    Geriatric

    32 mg/day PO for syrup and tablets; FDA-approved labeling for inhaler recommends not exceeding 12 puffs/day; FDA-approved labeling for nebulizer solution for oral inhalation recommends not exceeding 4 doses/day or 10 mg/day (0.083% or 0.5% nebulizer solution), 2.5 mg/day (0.63 mg/3 mL nebulizer solution), and 5 mg/day (1.25 mg/3 mL nebulizer solution). Higher maximum dosages for inhalation products have been recommended in NAEPP guidelines for acute exacerbations of asthma.

    Adolescents

    15 to 17 years: 32 mg/day PO for syrup and tablets; FDA-approved labeling for inhaler recommends not exceeding 12 puffs/day; FDA-approved labeling for nebulizer solution for oral inhalation recommends not exceeding 4 doses/day or 10 mg/day (0.083% or 0.5% nebulizer solution), 2.5 mg/day (0.63 mg/3 mL nebulizer solution), and 5 mg/day (1.25 mg/3 mL nebulizer solution). Higher maximum dosages for inhalation products have been recommended in NAEPP guidelines for acute exacerbations of asthma.
    13 to 14 years: 24 mg/day PO for syrup; 32 mg/day PO for tablets; FDA-approved labeling for inhaler recommends not exceeding 12 puffs/day; FDA-approved labeling for nebulizer solution for oral inhalation recommends not exceeding 4 doses/day or 10 mg/day (0.083% or 0.5% nebulizer solution), 2.5 mg/day (0.63 mg/3 mL nebulizer solution), and 5 mg/day (1.25 mg/3 mL nebulizer solution). Higher maximum dosages for inhalation products have been recommended in NAEPP guidelines for acute exacerbations of asthma.

    Children

    6 to 12 years: 24 mg/day PO for syrup and tablets; FDA-approved labeling for inhaler recommends not exceeding 12 puffs/day; FDA-approved labeling for nebulizer solution for oral inhalation recommends not exceeding 4 doses/day or 10 mg/day (0.083% or 0.5% nebulizer solution), 2.5 mg/day (0.63 mg/3 mL nebulizer solution), and 5 mg/day (1.25 mg/3 mL nebulizer solution). Higher maximum dosages for inhalation products have been recommended in NAEPP guidelines for acute exacerbations of asthma.
    4 to 5 years: 0.6 mg/kg/day PO (Max: 12 mg/day PO) for albuterol syrup; FDA-approved labeling for inhaler recommends not exceeding 12 puffs/day; FDA-approved labeling for nebulizer solution for oral inhalation recommends not exceeding 4 doses/day or 10 mg/day (0.083% or 0.5% nebulizer solution), 2.5 mg/day (0.63 mg/3 mL nebulizer solution), and 5 mg/day (1.25 mg/3 mL nebulizer solution). Higher maximum dosages for inhalation products have been recommended in NAEPP guidelines for acute exacerbations of asthma.
    2 to 3 years: 0.6 mg/kg/day PO (Max: 12 mg/day PO) for albuterol syrup; FDA-approved labeling for nebulizer solution for oral inhalation recommends not exceeding 4 doses/day or 10 mg/day (0.083% or 0.5% nebulizer solution), 2.5 mg/day (0.63 mg/3 mL nebulizer solution), and 5 mg/day (1.25 mg/3 mL nebulizer solution). Higher maximum dosages for inhalation products have been recommended in NAEPP guidelines for acute exacerbations of asthma.
    1 year: Safety and efficacy have not been established; nebulizer inhalation maximum dependent on patient response and formulation used.

    Infants

    Safety and efficacy have not been established; nebulizer inhalation maximum dependent on patient response and formulation used.

    Neonates

    Safety and efficacy have not been established; nebulizer inhalation maximum dependent on patient response and formulation used.

    DOSING CONSIDERATIONS

    Hepatic Impairment

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

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available. Caution may be warranted during the administration of high doses in patients with renal impairment, as renal clearance is reduced.

    ADMINISTRATION

    Oral Administration

    Administer with meals to minimize gastric irritation.

    Oral Solid Formulations

    Swallow whole, do not chew or crush the extended-release tablets.

    Oral Liquid Formulations

    Administer using a calibrated measuring device.

    Inhalation Administration

    Aerosol inhalation (e.g., ProAir HFA, Ventolin HFA)
    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 first use by spraying four times into the air, away from the eyes and face. When the inhaler has not been used for a prolonged period, prime by spraying two to four (2 to 4) times into the air away from the face, according to the specific inhaler type.
    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 individual patient. However, in general, children < 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 3—5 inhalations per actuation.
    General administration instructions: Shake the inhaler well before each use. Take the cap off the mouthpiece. Hold the inhaler as directed for the inhaler type. Patient will breathe out through the mouth and push as much air from lungs as the patient can. Put the mouthpiece in the mouth and have patient close lips around it. Push the top of the canister all the way down while the patient breathes in deeply and slowly through the mouth. Right after the spray comes out, release the canister. After the patient has breathed in all the way, take the inhaler out of the mouth. The patient should hold breath as long as they can, up to 10 seconds, then breathe normally. If prescribed more sprays, wait 1 minute and shake the inhaler again. Repeat inhaler steps. Put the cap back on the mouthpiece after use.
    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 one person.
    Clean the plastic mouthpiece of the inhaler at least once a week; some manufacturers advocate daily cleaning. After removing the medication canister wash the mouthpiece in warm running water. Do not allow the medication canister to get wet. Shake excess water from the mouthpiece and verify that all medication build-up has been rinsed away. Allow the mouthpiece to air-dry before next use (e.g., over-night).
    Discard medication and inhaler after expired or once the labeled number of inhalations have been used, whichever comes first; some products may have an inhalation counter. Ventolin HFA expires 12 months after medication removal from foil pouch. Other products should be discarded when the labeled number of actuations have been used or by the expiration date printed on original packaging; whichever comes first.
     
    Powder for Inhalation (e.g., ProAir RespiClick)
    Instruct patient on proper inhalation technique.
    Before using for the first time, check the dose counter window to ensure that the inhaler is full and the number "200" is in the window. The dose counter will count down each time the mouthpiece cap is opened and closed. The dose counter only displays even numbers (example: 200, 198, 196, etc.) in the window.
    Hold the inhaler upright while opening the cap fully. When the cap is opened, a dose of albuterol will be activated for delivery of the medicine. Make sure a "click" sound is heard; if not, the inhaler may not be activated to give a dose of medicine.
    The cap should not be opened unless the patient is ready to take a dose; opening and closing the cap without inhaling a dose will waste the medicine and may damage the inhaler.
    The patient should breathe out through the mouth and push as much air from the lungs as they can. Be careful that the patient does not breathe out into the inhaler mouthpiece. Put the mouthpiece in the mouth and have patient close lips around it. The patient should breathe in deeply through the mouth, until their lungs feel completely full of air. Ensure that the vent above the mouthpiece is not blocked by the patient's lips or fingers. The patient should hold their breath for about 10 seconds or as long as they comfortably can.
    Remove the inhaler from the mouth.
    Check the dose counter on the back of the inhaler to make sure the dose was received.
    Close the cap over the mouthpiece after each use of the inhaler; make sure the cap closes firmly into place.
    To inhale another dose, close the cap and then repeat inhaler steps.
    The inhaler contains a powder and must be kept clean and dry at all times. Do not wash or put any part of the inhaler in water. If the mouthpiece needs cleaning, gently wipe it with a dry cloth or tissue.
    When there are "20" doses left, the dose counter will change to red; refill the prescription or contact the doctor for another prescription.
    Throw away the inhaler 13 months after removing it from the foil pouch for the first time, when the dose counter displays "0", or after the expiration date on the package, whichever comes first.
     
    Inhalation solution for nebulization
    For a 2.5 mg dose of albuterol, dilute 0.5 mL of a 0.5% solution for nebulization to a final volume of 3 mL with 0.9% Sodium Chloride Solution or use 3 mL of the commercially available 0.083% solution for nebulization. Deliver solution by nebulization over 5—15 minutes.
    The choice of using a mouthpiece versus a face mask must be made based on the skills and understanding of each individual patient.
    Using the 'blow by' technique (i.e., holding the face mask or open tube near the patient's nose and mouth) is not recommended.
    Some nebulizer solutions state a grace period of 1 week is allowed after removal from the foil pouch. Other products state that the vials should be stored in the foil pouch until time of use. Refer to the specific product for this information.

    STORAGE

    Generic:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Accuneb:
    - After removing from pouch, use product within one week
    - Avoid excessive heat (above 104 degrees F)
    - Do not store outside the pouch provided
    - Protect from light
    - Store between 36 to 77 degrees F
    Proair HFA:
    - Exposure to temperatures above 120 degrees F may cause bursting
    - Flammable, keep away from heat and flame
    - Store away from excessive heat and cold
    - Store between 59 to 77 degrees F
    ProAir RespiClick:
    - Avoid excessive humidity
    - Store away from excessive heat and cold
    - Store between 59 to 77 degrees F
    Proventil:
    - Store between 59 to 77 degrees F
    - Store inhaler with mouthpiece down
    Proventil HFA:
    - Store between 59 to 77 degrees F
    - Store inhaler with mouthpiece down
    Proventil Repetabs:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Respirol :
    - Store between 59 to 77 degrees F
    - Store inhaler with mouthpiece down
    Ventolin:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Ventolin HFA:
    - Store between 59 to 77 degrees F
    - Store inhaler with mouthpiece down
    Volmax:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    VoSpire ER:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Do not exceed recommended dosages of beta-agonists; fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma. The exact cause of death is unknown, but cardiac arrest after an unexpected development of a severe acute asthmatic crisis and subsequent hypoxia is suspected.

    Albuterol hypersensitivity, levalbuterol hypersensitivity, milk protein hypersensitivity

    Albuterol is contraindicated in patients with albuterol hypersensitivity, levalbuterol hypersensitivity, or hypersensitivity to any component of the specific dosage formulation. Albuterol inhalation powder (i.e., ProAir RespiClick) is contraindicated in patients with severe milk protein hypersensitivity since the formulation contains lactose, which contains milk proteins. 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 beta-agonists, albuterol can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, albuterol 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, thyroid disease

    Albuterol should be used with caution in patients with cardiovascular disorders including ischemic cardiac disease (coronary artery disease), hypertension, cardiac arrhythmias, tachycardia, or QT prolongation. In addition, beta-agonists should be avoided in patients with congenital long QT syndrome. Use albuterol with caution in patients with conditions that may increase the risk of QT prolongation including heart failure, bradycardia, myocardial infarction, 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 disease, 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, albuterol 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.

    Geriatric

    Reported clinical experience with inhaled albuterol has not identified any differences in safety, efficacy or clinical responsiveness with geriatric vs. younger adult patients. Geriatric patients may be more sensitive to the side effects of inhaled and systemic beta-agonists, especially tremor and tachycardia. Although not clearly established, airway responsiveness to albuterol may also change with age. 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 albuterol, can cause restlessness, increased heart rate, and anxiety.

    Hyperthyroidism, pheochromocytoma, seizure disorder, seizures, thyrotoxicosis

    Albuterol 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, diabetic ketoacidosis

    Use albuterol with caution in patients with diabetes mellitus. Large doses of intravenous racemic albuterol have been reported to aggravate preexisting diabetes mellitus and diabetic ketoacidosis. In addition, patients with diabetic ketoacidosis (DKA) typically have severe electrolyte imbalance. Serum potassium concentrations must be closely monitored during the treatment of DKA and albuterol may contribute to changes in serum potassium concentrations.

    Deterioration of asthma, paradoxical bronchospasm

    Paradoxical bronchospasm can occur after treatment with albuterol and can be life-threatening. If this occurs, albuterol should be discontinued immediately and supportive care provided as necessary. Additionally, increased albuterol 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 albuterol, appropriate evaluation of the patient and the treatment strategy is warranted, giving special consideration to corticosteroid therapy. Albuterol 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 albuterol therapy is instituted.

    Labor, obstetric delivery, pregnancy

    There are no randomized clinical studies of use of albuterol during pregnancy. Available data from published epidemiological studies and post-marketing case reports of pregnancy outcomes following inhaled albuterol use do not consistently demonstrate a risk of major birth defects or miscarriage. In animal reproduction studies, when albuterol sulfate was administered subcutaneously to pregnant mice there was evidence of cleft palate at less than and up to 9 times the maximum recommended human daily inhalation dose (MRHDID).. In women with poorly or moderately controlled asthma, there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Pregnant women should be closely monitored and medication adjusted as necessary to maintain optimal control. The 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group include short-acting inhaled beta-2 agonists as first line therapy for mild intermittent asthma during pregnancy, if treatment is required. Albuterol is preferred over other short-acting beta-2 agonists due to extensive safety-related information during pregnancy. However, there is no evidence of fetal injury with the use of other short-acting inhaled beta-2 agonists, and maintaining a previously established treatment regimen may be more beneficial to the patient. Due to the potential for beta-agonist interference with uterine contractility, the use of albuterol for acute relief of bronchospasm during labor and obstetric delivery should be restricted to those patients in whom the benefits clearly outweigh the risks. Additionally, albuterol 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.

    Breast-feeding

    There are no available systematic human data evaluating the presence of albuterol in human milk, the effects on the breastfed child, or the effects on milk production. According to the 2004 recommendations of the National Asthma Education and Prevention Program for managing asthma during pregnancy, there is currently no contraindication for use of short-acting inhaled beta-2 agonists, including albuterol, during lactation. Plasma concentrations of albuterol after inhalation of therapeutic doses are very low in humans and substantially lower than systemically-administered albuterol. If present in breast milk, albuterol has a low oral bioavailability. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Children, infants, neonates

    Albuterol is often prescribed in children and infants, including neonates, in the clinical setting, and recommendations for use exist in established asthma treatment guidelines. Nebulizer administration is helpful for acute asthma exacerbations, or, when proper use of a metered dose inhaler (MDI) device is difficult for the child in outpatient settings. Metered dose inhalers (MDIs) are also used commonly in even young children for the treatment of asthma. A spacer device is often recommended for use with metered-dose inhalation solution inhalers to assist coordination of proper medication delivery; however, a spacer or volume holding chamber should not be used with the albuterol inhalation powder inhaler. The safety and effectiveness of albuterol inhalation powder has not yet established for children below the age of 12 years; however, single-dose clinical studies have included children as young as 4 years of age; very young children often have difficulty with the inspiratory flow required for proper use of dry powder inhalers. The safety and effectiveness of oral albuterol immediate-release and extended-release tablets has not been established for children below the age of 6 years ; albuterol syrup is approved for use in children 2 years and older.

    Renal impairment

    The pharmacokinetics of albuterol were studied in a small number of subjects with creatinine clearances between 7—53 mL/minute in comparison to healthy volunteers. The half-life was unchanged; however albuterol clearance was decreased by 67% in those with renal impairment. The manufacturer recommends caution during administration of high doses of inhaled albuterol to patients with renal impairment.

    MAOI therapy

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

    ADVERSE REACTIONS

    Severe

    bronchospasm / Rapid / 8.0-15.4
    arrhythmia exacerbation / Early / Incidence not known
    atrial fibrillation / Early / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    muscle paralysis / Delayed / Incidence not known

    Moderate

    excitability / Early / 1.0-20.0
    palpitations / Early / 0-10.0
    sinus tachycardia / Rapid / 1.0-10.0
    hypertension / Early / 0-5.0
    chest pain (unspecified) / Early / 0-3.0
    ataxia / Delayed / 0-3.0
    dysphonia / Delayed / 0-3.0
    edema / Delayed / 0-3.0
    glossitis / Early / 0-3.0
    dyspnea / Early / 0-3.0
    lymphadenopathy / Delayed / 0.9-2.6
    migraine / Early / 1.0-2.0
    wheezing / Rapid / 1.0-1.5
    urinary retention / Early / 0-1.0
    conjunctivitis / Delayed / 1.0-1.0
    QT prolongation / Rapid / Incidence not known
    ST-T wave changes / Rapid / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    hypotension / Rapid / Incidence not known
    hypokalemia / Delayed / Incidence not known
    angina / Early / Incidence not known
    peripheral vasodilation / Rapid / Incidence not known
    supraventricular tachycardia (SVT) / Early / Incidence not known
    metabolic acidosis / Delayed / Incidence not known

    Mild

    tremor / Early / 0-37.9
    infection / Delayed / 0-21.0
    headache / Early / 3.0-18.8
    rhinitis / Early / 4.0-16.0
    nausea / Early / 0-15.0
    pharyngitis / Delayed / 7.0-14.0
    throat irritation / Early / 6.0-10.0
    vomiting / Early / 4.2-7.0
    dizziness / Early / 0-7.0
    muscle cramps / Delayed / 0-6.9
    fever / Early / 6.0-6.0
    cough / Delayed / 0-5.0
    dyspepsia / Early / 0-5.0
    musculoskeletal pain / Early / 3.0-5.0
    hyperkinesis / Delayed / 0-4.0
    insomnia / Early / 1.0-3.1
    xerostomia / Early / 0-3.0
    flatulence / Early / 0-3.0
    epistaxis / Delayed / 1.0-3.0
    abdominal pain / Early / 0-3.0
    anxiety / Delayed / 0-3.0
    diarrhea / Early / 0-3.0
    drowsiness / Early / 0-3.0
    hyperhidrosis / Delayed / 0-3.0
    laryngitis / Delayed / 0-3.0
    otalgia / Early / 0-3.0
    tinnitus / Delayed / 0-3.0
    weakness / Early / 0-2.0
    urticaria / Rapid / 0.9-1.7
    malaise / Early / 1.5-1.5
    nightmares / Early / 1.0-1.0
    emotional lability / Early / 1.0-1.0
    agitation / Early / 1.0-1.0
    flushing / Rapid / 0-1.0
    restlessness / Early / 0-1.0
    irritability / Delayed / 0-1.0
    nasal congestion / Early / 1.0-1.0
    rash (unspecified) / Early / Incidence not known
    tooth discoloration / Delayed / Incidence not known
    hoarseness / Early / Incidence not known
    eructation / Early / Incidence not known
    hyperactivity / Early / Incidence not known
    vertigo / Early / 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; 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: (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; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (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; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (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; Dextromethorphan; Guaifenesin; Phenylephrine: (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; Dextromethorphan; Phenylephrine: (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; Dextromethorphan; Pseudoephedrine: (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; 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: (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; Pseudoephedrine: (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.
    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: (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.
    Alfuzosin: (Minor) Based on electrophysiology studies performed by the manufacturer, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. The manufacturer warns that the QT effect of alfuzosin should be considered prior to administering the drug to patients taking other medications known 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. 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.
    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: (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.
    Amphetamine; Dextroamphetamine Salts: (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.
    Amphetamine; Dextroamphetamine: (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.
    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: (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.
    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.
    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: (Moderate) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Both atomoxetine and beta-agonists are considered drugs with a possible risk of torsade de pointes (TdP); therefore, the combination should be used cautiously and with close monitoring. Other cardiovascular adverse effects of beta-agonists, such as increased heart rate and blood pressure, have been shown to be potentiated by the coadministration of atomoxetine. Albuterol 600 mcg IV over 2 hours when combined with atomoxetine 60 mg twice a day for 5 days resulted in additional increases in heart rate and blood pressure over that seen alone with albuterol. Exercise caution if beta-agonists and atomoxetine are coadministered; consider monitoring heart rate and blood pressure initially. The interaction may be less likely with inhaled beta-agonists versus those given systemically.
    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: (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.
    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: (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.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (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.
    Brompheniramine; Pseudoephedrine: (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.
    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: (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.
    Carbetapentane; Diphenhydramine; Phenylephrine: (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.
    Carbetapentane; Guaifenesin; Phenylephrine: (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.
    Carbetapentane; Phenylephrine: (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.
    Carbetapentane; Phenylephrine; Pyrilamine: (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.
    Carbetapentane; Pseudoephedrine: (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.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (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.
    Carbinoxamine; Hydrocodone; Phenylephrine: (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.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (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.
    Carbinoxamine; Phenylephrine: (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.
    Carbinoxamine; Pseudoephedrine: (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.
    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: (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.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (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.
    Chlophedianol; Guaifenesin; Phenylephrine: (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.
    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: (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.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (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.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (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.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (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.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (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.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (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.
    Chlorpheniramine; Phenylephrine: (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.
    Chlorpheniramine; Pseudoephedrine: (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.
    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.
    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.
    Codeine; Phenylephrine; Promethazine: (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. (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.
    Cyclobenzaprine: (Minor) Cyclobenzaprine is structurally similar to tricyclic antidepressants (TCAs). TCAs have been reported to prolong the QT interval, especially when given in excessive doses (or in overdosage settings). Cyclobenzaprine is associated with a possible risk of QT prolongation and torsade de pointes (TdP), particularly in the event of acute overdose. Drugs with a possible risk for QT prolongation that should be used cautiously with cyclobenzaprine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects, usually at higher doses and/or when associated with hypokalemia.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir, include beta-agonists.
    Dasatinib: (Minor) In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Cautious dasatinib administration is recommended to patients who have or may develop QT prolongation, such as patients taking drugs that lead to QT prolongation. Drugs with a possible risk for QT prolongation that should be used cautiously with dasatinib include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Daunorubicin: (Minor) Acute cardiotoxicity can occur during administration of daunorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Degarelix: (Minor) Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with degarelix 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.
    Desiccated Thyroid: (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.
    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: (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.
    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: (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.
    Dextroamphetamine: (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.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (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.
    Dextromethorphan; Guaifenesin; Phenylephrine: (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.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (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.
    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: (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.
    Diphenhydramine; Hydrocodone; Phenylephrine: (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.
    Diphenhydramine; Phenylephrine: (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.
    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: (Severe) Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of 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. Because of the potential for TdP, use of beta-agonists with dofetilide is contraindicated.
    Dolasetron: (Minor) Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram (ECG). Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with dolasetron 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.
    Donepezil: (Minor) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include the beta-agonists.
    Donepezil; Memantine: (Minor) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include the 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.
    Doxorubicin: (Minor) Acute cardiotoxicity can occur during administration of doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with 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) Although data are limited, coadministration of efavirenz and beta-agonists may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with 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) Although data are limited, coadministration of efavirenz and beta-agonists may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with 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) Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR 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.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Minor) Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR 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.
    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.
    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: (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.
    Epirubicin: (Minor) Acute cardiotoxicity can occur during the administration of epirubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with epirubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    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) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as beta-agonists, should be done with caution and close monitoring.
    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) Ezogabine has been associated with QT prolongation. The manufacturer of ezogabine recommends caution during concurrent use of medications known to increase the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with ezogabine 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.
    Fexofenadine; Pseudoephedrine: (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.
    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) Fluconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with fluconazole 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.
    Fluoxetine: (Minor) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include beta-agonists.
    Fluoxetine; Olanzapine: (Minor) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include beta-agonists. (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.
    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) 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. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with gemifloxacin include the beta-agonists. Beta-agonists may cause adverse cardiovascular effects, usually at higher doses and/or when associated with hypokalemia.
    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.
    Goserelin: (Minor) Androgen deprivation therapy (e.g., goserelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with goserelin include beta-agonists.
    Granisetron: (Minor) Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with granisetron include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    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: (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.
    Guaifenesin; Phenylephrine: (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.
    Guaifenesin; Pseudoephedrine: (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.
    Guarana: (Moderate) Caffeine, an active constituent of guarana, is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Use of guarana should be avoided with beta-agonists. When combined with any of these medications, nervousness, irritability, insomnia, and/or cardiac arrhythmias may result.
    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) 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. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known 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.
    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.
    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: (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.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (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.
    Hydrocodone; Pseudoephedrine: (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.
    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) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists, like albuterol, 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.
    Ibuprofen; Pseudoephedrine: (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.
    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.
    Idarubicin: (Minor) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    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: (Major) Itraconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with itraconazole include 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) Lapatinib can prolong the QT interval. Lapatinib should be administered with caution to patients who have or may develop prolongation of QTc such as patients taking anti-arrhythmic medicines or other medicinal products that lead to QT prolongation. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with lapatinib 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.
    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) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Leuprolide; Norethindrone: (Minor) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include 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) Avoid levofloxacin in patients taking drugs that can result in prolongation of the QT interval, such as beta-agonists. Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Rare cases of torsade de pointes (TdP) have been reported during postmarketing surveillance in patients receiving levofloxacin. Beta-agonists may cause adverse cardiovascular effects, usually at higher doses and/or when associated with hypokalemia.
    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.
    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.
    Liotrix: (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: (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.
    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.
    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: (Moderate) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir, include beta-agonists. (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: (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.
    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.
    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: (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.
    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: (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.
    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, RU-486: (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: (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.
    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) Nilotinib prolongs the QT interval. Coadministration of nilotinib and other drugs that prolong the QT interval, is not advised. The manufacturer recommends interruption of nilotinib treatment as a possible alternative. If concurrent administration is unavoidable, closely monitor the patient for QT interval prolongation. Drugs that should be used with caution with nilotinib 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. Additionally, indacaterol is a CYP3A4, CYP2D6, and P-glycoprotein (P-gp) substrate, and nilotinib is a competitive inhibitor of CYP3A4, CYP2D6, and P-gp. Increased concentrations of indacaterol are likely if it is coadministered with nilotinib.
    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) Until further data are available, administer octreotide cautiously in patients receiving drugs that prolong the QT interval, such as the beta-agonists. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Ofloxacin: (Minor) Some quinolones, including ofloxacin, have been associated with QT prolongation and infrequent cases of arrhythmia. Post-marketing surveillance for ofloxacin has identified very rare cases of torsade de pointes (TdP). Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with ofloxacin 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.
    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.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir, include beta-agonists.
    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) Monitor electrolytes and ECGs for QT prolongation if coadministration of short-acting beta-agonists such as albuterol and levalbuterol with osimertinib is necessary; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. 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.
    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; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, paliperidone should be avoided in combination with other drugs that may cause QT prolongation. If coadministration is considered necessary and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. 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.
    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) Cautious use of pasireotide and a beta-agonist is needed, as coadministration may have additive effects on the prolongation of 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. 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.
    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: (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.
    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: (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.
    Phentermine; Topiramate: (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.
    Phenylephrine: (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.
    Phenylephrine; Promethazine: (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. (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.
    Posaconazole: (Minor) Posaconazole has been associated with QT prolongation and in rare cases, torsade de pointes. When possible, avoid concurrent administration of posaconazole with other drugs that may also 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.
    Prilocaine; Epinephrine: (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.
    Primaquine: (Minor) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with primaquine include 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: (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.
    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.
    Regadenoson: (Minor) Regadenoson has been associated with QT prolongation. Drugs with a possible risk for QT prolongation that should be used cautiously with regadenoson 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.
    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) Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR 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.
    Risperidone: (Minor) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes(TdP); however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP are noted by the manufacturer, primarily in the overdosage setting. Risperidone should be used cautiously with other agents that might prolong the QT interval, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with risperidone 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.
    Ritonavir: (Moderate) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir, include 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) There have been post-marketing reports of QT prolongation and torsade de pointes (TdP) during treatment with sertraline; therefore, caution is advisable when using sertraline in patients with risk factors for QT prolongation, including concurrent use of other drugs that prolong the QTc interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sertraline 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. The action of beta-agonists on the cardiovascular system may be potentiated.
    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.
    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) Sorafenib has been associated with QT prolongation. If sorafenib and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sorafenib 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.
    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.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Sunitinib: (Minor) Sunitinib can prolong the QT interval. Administer sunitinib with caution in patients taking drugs with the potential to induce QT prolongation including 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.
    Tacrolimus: (Minor) Tacrolimus causes QT prolongation. Other agents associated with a possible risk for QT prolongation that should be used cautiously with tacrolimus 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.
    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) Telavancin has been associated with QT prolongation. According to the manufacturer, telavancin should be used with caution when prescribing other agents also known to prolong the QT interval (e.g., 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.
    Telithromycin: (Minor) Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with telithromycin 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. In addition, telithromycin is an inhibitor of CYP3A4 and may increase salmeterol concentrations; use salmeterol with caution.
    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.
    Tizanidine: (Minor) Beta-agonists should be used cautiously with tizanidine. Tizanidine administration may result in 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.
    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) Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with toremifene 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.
    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) Androgen deprivation therapy (e.g., triptorelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with triptorelin include beta-agonists.
    Vandetanib: (Minor) Vandetanib can prolong the QT interval in a concentration-dependent manner. Torsade de pointes (TdP) and sudden death have been reported in patients receiving vandetanib. Avoid the concomitant use of vandetanib with drugs known to prolong the QT interval. If a drug that can prolong the QT interval is given to a patient already taking vandetanib and no alternative therapy exists, perform more frequent monitoring of the QT interval. An ECG is needed if a drug that causes QT prolongation is started. If QTcF is > 500 ms, interrupt vandetanib dosing until the QTcF is < 450 ms - vandetanib may then be resumed at a reduced dose. Drugs that may cause QT prolongation that should be used with caution with vandetanib 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.
    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: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including 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.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no available systematic human data evaluating the presence of albuterol in human milk, the effects on the breastfed child, or the effects on milk production. According to the 2004 recommendations of the National Asthma Education and Prevention Program for managing asthma during pregnancy, there is currently no contraindication for use of short-acting inhaled beta-2 agonists, including albuterol, during lactation. Plasma concentrations of albuterol after inhalation of therapeutic doses are very low in humans and substantially lower than systemically-administered albuterol. If present in breast milk, albuterol has a low oral bioavailability. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Mechanism of Action: Albuterol is a moderately selective beta2-adrenergic agonist that stimulates receptors of the smooth muscle in the lungs, uterus, and vasculature supplying skeletal muscle. Albuterol is racemic beta-agonist, comprised of an equal mixture of R- and S-isomers. The R-isomer, known as levalbuterol, is primarily responsible for bronchodilation. Although not confirmed during clinical trials, the S-isomer of albuterol has bronchoconstrictive properties in animal models.Intracellularly, the actions of albuterol are mediated by cyclic AMP, the production of which is augmented by beta2-stimulation. Albuterol 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.Albuterol 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. Albuterol is an effective adjunctive treatment for hyperkalemia; beta2-adrenergic stimulation results in intracellular accumulation of serum potassium due to stimulation of the Na/K ATPase pump, leading to moderate degrees of hypokalemia.

    PHARMACOKINETICS

    Albuterol can be administered as oral tablets or oral solution, but is more commonly administered by oral inhalation. Albuterol crosses the blood-brain barrier and may cross the placenta. The liver metabolizes albuterol extensively to inactive compounds. Excretion of albuterol occurs through the urine and feces. The elimination half-life of albuterol ranges from 2.7—6 hours, with orally administered albuterol having a shorter half-life than the inhaled product.

    Oral Route

    When administered orally, albuterol is well absorbed through the GI tract. Onset of action begins within 30 minutes, peak levels are reached in 2—3 hours, and duration of action is 4—6 hours for the conventional-release tablets and 8—12 hours for the sustained-release product. After oral administration, 75% of a dose is excreted in urine within 72 hours as metabolites; 4% may be found in feces.

    Inhalation Route

    Following oral inhalation, albuterol is absorbed over several hours from the respiratory tract. It is postulated from studies with other inhaled bronchodilators that most of an albuterol inhaled dose (approximately 90%) is actually swallowed and absorbed through the GI tract. The systemic exposure in children 6 to 11 years of age is similar to that of adults after 180 mcg single dose oral inhalation. Onset of bronchodilation occurs within 5 to 15 minutes after oral inhalation, peaks in 0.5 to 2 hours, and lasts 2 to 6 hours. Administration via nebulization does not appear to significantly alter the pharmacokinetics of albuterol. After oral inhalation, 80% to 100% of a dose is excreted via the kidneys within 72 hours; up to 10% may be eliminated in feces.