PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Respiratory Short-Acting Beta-2 Agonists (SABA)

    DEA CLASS

    Rx

    DESCRIPTION

    Moderately selective short-acting beta-2 receptor agonist (SABA); r-enantiomer of racemic albuterol; available as oral inhaler and nebulizer treatment
    Used clinically in adult and pediatric patients for acute bronchospasm due to asthma as a reliever therapy and for asthma exacerbations; also used in adults with COPD
    Clinical activity similar to racemic albuterol

    COMMON BRAND NAMES

    Xopenex, Xopenex Pediatric

    HOW SUPPLIED

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

    DOSAGE & INDICATIONS

    For asthma exacerbation (e.g., primary care or acute care management).
    Nebulized Inhalation dosage (solution for nebulization; various concentrations)
    Adults


    1.25 mg via nebulizer every 20 minutes for the first hour for mild to moderate exacerbation. After the first hour, 1.25 mg every 3 to 4 hours and up to 1.25 mg every 1 to 2 hours, or more often. Typical dose range: 0.63 mg to 1.25 mg via nebulizer 3 times daily, every 6 to 8 hours.

    Children and Adolescents 12 years and older

    1.25 mg via nebulizer every 20 minutes for the first hour for mild to moderate exacerbation. After the first hour, 1.25 mg every 3 to 4 hours and up to 1.25 mg every 1 to 2 hours, or more often. Typical dose range: 0.63 mg to 1.25 mg via nebulizer 3 times daily, every 6 to 8 hours.

    Children 6 to 11 years

    1.25 mg via nebulizer every 20 minutes for the first hour for acute exacerbation, with reassessment after that (further dosing not specified). Typical dose range: 0.31 mg to 0.63 mg via nebulizer 3 times daily, every 6 to 8 hours.

    Infants† and Children† 5 years and younger

    1.25 mg via nebulizer every 20 minutes for the first hour for acute exacerbation, with reassessment after that (further dosing not specified).

    For transient increase in bronchospasm (e.g., episodic wheezing) as asthma reliever therapy.
    Oral Inhalation dosage (inhalation aerosol, e.g., Xopenex HFA)
    Adults

    90 mcg (2 actuations of 45 mcg/actuation) via oral inhalation every 4 to 6 hours as needed for bronchospasm; in some patients 45 mcg (1 actuation) every 4 hours may be sufficient. Max: 12 actuations/day (540 mcg/day).

    Children and Adolescents 4 years and older

    90 mcg (2 actuations of 45 mcg/actuation) via oral inhalation every 4 to 6 hours as needed for bronchospasm; in some patients 45 mcg (1 actuation) every 4 hours may be sufficient. Max: 12 actuations/day (540 mcg/day).

    Nebulized Inhalation dosage (solution for nebulization; various concentrations)
    Adults

    0.63 to 1.25 mg via nebulizer 3 times daily (every 6 to 8 hours) as needed. Max: 3 doses/day (3.75 mg/day).

    Children and Adolescents 12 to 17 years

    0.63 to 1.25 mg via nebulizer 3 times daily (every 6 to 8 hours) as needed. Max: 3 doses/day (3.75 mg/day).

    Children 6 to 11 years

    0.31 to 0.63 mg via nebulizer 3 times daily as needed. Max: 3 doses/day (1.89 mg/day).

    For the treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD) (e.g., chronic bronchitis or emphysema).
    Oral Inhalation dosage (inhalation aerosol, e.g., Xopenex HFA)
    Adults

    90 mcg (2 actuations of 45 mcg/actuation) via oral inhalation every 4 to 6 hours as needed; in some patients, 45 mcg (1 actuation) every 4 hours may be sufficient. More frequent administration or a larger number of inhalations is not routinely recommended. The optimal dosage of levalbuterol for the treatment of an acute COPD exacerbation is not established; adjust dose according to clinical symptoms or the development of adverse effects. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for COPD, levalbuterol may be used as first-line therapy in Group A and may also be used in Groups B, C, and D for additional symptom control. Short-acting beta-2 agonists (SABAs) are preferred therapy for the treatment of acute COPD exacerbation, used with or without a short-acting anticholinergic. No significant differences in FEV1 have been demonstrated between metered-dose inhalers (with or without a spacer) and nebulizers with SABAs in clinical trials; nebulizers may be more convenient for patients that are more acutely ill.[63765]

    Nebulized Inhalation dosage (solution for nebulization; various concentrations)
    Adults

    Initially, 0.63 mg via nebulizer 3 times per day, given every 6 to 8 hours. Patients who do not respond adequately may benefit from a dosage of 1.25 mg via nebulizer 3 times per day.[51793] Optimal dosing for a COPD exacerbation is not established; adjust dose according to clinical symptoms or the development of adverse effects.[55976] According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for COPD, levalbuterol may be used as first-line therapy in Group A and may also be used in Groups B, C, and D for additional symptom control. Short-acting beta-2 agonists (SABAs) are preferred therapy for the treatment of acute COPD exacerbation, used with or without a short-acting anticholinergic. No significant differences in FEV1 have been demonstrated between metered-dose inhalers (with or without a spacer) and nebulizers with SABAs in clinical trials; nebulizers may be more convenient for patients that are more acutely ill.[63765]

    For exercise-induced bronchospasm prophylaxis†.
    Oral Inhalation dosage (inhalation aerosol, e.g., Xopenex HFA)
    Adults

    90 mcg (2 actuations of 45 mcg/actuation) via oral inhalation, administered 15 minutes (range, 5 to 20 minutes) before exercise. A controller agent (e.g., daily inhaled corticosteroid) is recommended to be used along with as-needed and pre-exercise SABAs like levalbuterol.

    Children and Adolescents 4 to 17 years

    90 mcg (2 actuations of 45 mcg/actuation) via oral inhalation, administered 15 minutes (range, 5 to 20 minutes) before exercise. A controller agent (e.g., daily inhaled corticosteroid) is recommended to be used along with as-needed and pre-exercise SABAs like levalbuterol.

    For the adjunctive emergency acute treatment of hyperkalemia† until hemodialysis is available.
    Nebulizer Inhalation dosage (solution for nebulization; various concentrations)
    Adults†

    Single doses of levalbuterol 2.5 mg have been administered in one trial of healthy adults and are reportedly as effective as albuterol 10 mg nebulized. K+ concentrations usually fall within 30 minutes of treatment. Levalbuterol reportedly results in fewer reported side effects than albuterol; however, it is more costly. Beta-agonists can be effective treatments for hyperkalemia via beta-adrenergic induction of potassium (K+) uptake. However, they are a temporary adjunctive measure.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

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

    Geriatric

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

    Adolescents

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

    Children

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

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustments are needed.

    Renal Impairment

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

    ADMINISTRATION

    Inhalation Administration
    Oral Inhalation Administration

    Oral Inhalation (inhalation aerosol; metered-dose inhaler [MDI])
    Instruct the patient and/or caregiver on proper inhalation technique. Make sure the canister is firmly seated in the plastic mouthpiece actuator before each use. Shake the inhaler well. Prime the inhaler prior to the initial use by releasing 4 sprays into the air, away from the eyes and face. If not used for more than 3 days, re-prime the inhaler.
    For patients of any age unable to coordinate inhalation and actuation, a spacer or valved holding chamber (VHC) may be beneficial.
    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 younger than 4 years require administration with a tight-fitting face mask and spacer/VHC device to achieve optimal delivery. If a face mask is used, allow 5 to 6 inhalations per actuation. Administer 1 puff at a time.
    If the patient is using other inhalers, instruct them to use levalbuterol first and wait 5 minutes, then use other inhalers as directed.
    After administration, instruct patient to rinse mouth with water to minimize dry mouth.
    The blue actuator (mouthpiece) supplied with levalbuterol (Xopenex HFA) should not be used with any other product canisters; conversely, actuators from other products should not be used with the levalbuterol (Xopenex HFA) canister.
    The dose indicator on the canister indicates the number of remaining inhalations. The dose indication display will move every tenth actuation. Towards the end of the usable inhalations, the color behind the number in the dose indicator window will change to red. Discard when the dose indicator display window shows zero.
    Clean the plastic mouthpiece of the inhaler at least once a week. After removing the medication canister wash the mouthpiece in warm running water. Shake excess water from the mouthpiece. Allow the actuator to air-dry completely. Blockage from medicine build up is more likely to occur if the actuator is not allowed to air-dry thoroughly. If build-up occurs, then washing the actuator will remove the blockage.
    To avoid the spread of infection, do not use the inhaler for more than one person.
     
    Inhalation Solution for Nebulization
    For 3 mL inhalation solution vials: No dilution is necessary; the single-dose vials are ready-to-use.
    For 0.5 mL inhalation solution concentrate vials: Squeeze entire contents of vial into nebulizer reservoir; then, dilute solution to a final volume of 3 mL with sterile 0.9% NaCl Injection, and gently swirl nebulizer reservoir to mix.
    NOTE: For dosages less than 1.25 mg, the 3 mL inhalation solution vials must be used.
    Deliver solution by nebulization over 5 to 15 minutes.
    According to the manufacturer, the compatibility of levalbuterol inhalation solution with other drugs administered by nebulization has not been established; however, clinical guidelines state that levalbuterol nebulizer solution and budesonide suspension for nebulization are compatible in the same nebulizer.
    Safety and efficacy have been established when administered via PARI LC Jet or PARI LC Plus nebulizers and via PARI Master Dura-Neb 2000 or Dura-Neb 3000 compressors.
    The choice of using a mouthpiece versus a face mask must be made based on the skills and understanding of each 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.
    To avoid microbial contamination, aseptic technique should be used each time a multi-dose bottle is opened. Precautions should be taken to prevent contact of dropper tip with any surface, including nebulizer reservoir and ventilatory equipment. Each multi-dose bottle should be used for only 1 patient.
    Discard the vial if the solution is not colorless.
    Storage: Protect from light.
    For 3 mL inhalation solution vials: Unit-dose vials should be stored in the protective foil pouch. If a vial is removed from the pouch and not used immediately, protect from light and use within 1 week. Once the protective foil pouch is opened use all contained vials within 2 weeks.
    For 0.5 mL inhalation solution concentrate vials: Use the contents of the vial immediately after the foil pouch is opened; do not store for future use.

    STORAGE

    Xopenex:
    - After opening the foil pouch, product should be used within 2 weeks
    - Avoid excessive heat (above 104 degrees F)
    - Discard product if solution is not colorless
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store unused product in foil pouch
    Xopenex Pediatric:
    - After opening the foil pouch, product should be used within 2 weeks
    - Avoid excessive heat (above 104 degrees F)
    - Discard product if solution is not colorless
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store unused product in foil pouch

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

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

    Albuterol hypersensitivity, angioedema, levalbuterol hypersensitivity

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

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

    Levalbuterol also should be used cautiously in patients with hyperthyroidism (thyrotoxicosis, thyroid disease), pheochromocytoma, unusual responsiveness to other sympathomimetic amines, or a seizure disorder (history of seizures). Pheochromocytoma may increase the risk of prolonging the QT interval when using levalbuterol.

    Apheresis, AV block, bradycardia, cardiac arrhythmias, cardiac disease, cardiomyopathy, celiac disease, coronary artery disease, females, fever, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, myocardial infarction, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE), tachycardia

    Levalbuterol should be used with caution in patients with cardiovascular disorders including ischemic cardiac disease (coronary artery disease), hypertension, cardiac arrhythmias, tachycardia, or QT prolongation. Beta-agonists should also be avoided in patients with suspected or known congenital long QT syndrome due to the risk for torsade de pointes and QT prolongation. Use levalbuterol with caution in patients with conditions that may increase the risk of QT prolongation including bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation. Significant changes in systolic and diastolic blood pressures and heart rate could be expected to occur in some patients after use of any beta-adrenergic bronchodilator. As with other beta-adrenergic agonist medications, levalbuterol may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects including QT prolongation. The decrease is usually transient, not requiring supplementation. Correct pre-existing hypokalemia prior to beta-agonist administration.

    Renal failure, renal impairment

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

    Diabetes mellitus

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

    Deterioration of asthma, paradoxical bronchospasm

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

    Children, infants, neonates

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

    Labor, obstetric delivery, pregnancy

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

    Breast-feeding

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

    MAOI therapy

    Beta-2 agonists, like levalbuterol, should be administered with extreme caution to patients being treated with MAOI therapy.

    Geriatric

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

    ADVERSE REACTIONS

    Severe

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

    Moderate

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

    Mild

    headache / Early / 7.6-11.9
    vomiting / Early / 11.0-11.0
    pharyngitis / Delayed / 3.0-10.4
    fever / Early / 3.0-9.1
    tremor / Early / 6.8-6.8
    diarrhea / Early / 1.5-6.0
    cough / Delayed / 1.4-4.0
    dizziness / Early / 1.4-3.0
    asthenia / Delayed / 3.0-3.0
    sinusitis / Delayed / 1.4-2.7
    dyspepsia / Early / 1.4-2.7
    muscle cramps / Delayed / 0-2.7
    epistaxis / Delayed / 0-2.0
    syncope / Early / 0-2.0
    ocular pruritus / Rapid / 0-2.0
    acne vulgaris / Delayed / 0-2.0
    anxiety / Delayed / 0-2.0
    paresthesias / Delayed / 0-2.0
    insomnia / Early / 0-2.0
    nausea / Early / 0-2.0
    xerostomia / Early / 0-2.0
    myalgia / Early / 1.5-2.0
    dysmenorrhea / Delayed / 0-2.0
    chills / Rapid / 0-2.0
    abdominal pain / Early / 1.5-1.5
    vertigo / Early / Incidence not known
    infection / Delayed / Incidence not known
    gastroesophageal reflux / Delayed / Incidence not known

    DRUG INTERACTIONS

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

    PREGNANCY AND LACTATION

    Pregnancy

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

    MECHANISM OF ACTION

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

    PHARMACOKINETICS

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

    Inhalation Route

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