Serevent Diskus

Respiratory Long-Acting Beta-2 Agonists (LABA)

Inhalation Administration Oral Inhalation Administration

NOTE: Never use salmeterol to treat acute bronchospasm. If any patient who uses salmeterol experiences wheezing that worsens and cannot be relieved during an acute asthma attack, they should be instructed to seek immediate medical attention.
 
Powder for oral inhalation (Serevent Diskus)
One Diskus blister (one inhalation) contains 50 mcg of salmeterol as the xinafoate salt.
Instruct the patient to open and prepare mouthpiece of Diskus device and slide device lever to activate the first dose (see package instructions). Do not advance the lever more than once at any one time as this will release further doses that will be wasted. Holding the Diskus mouthpiece level to, but away from, the mouth, exhale; be careful never to breathe into the Diskus inhaler. Then, put the mouthpiece to the lips and breathe in the dose quickly and deeply through the mouth. Remove the Diskus from the mouth, hold breath for at least 10 seconds, and then exhale slowly. 
Instruct patient to close the Diskus, which will also reset the dose lever for the next scheduled dose.
Most patients can either feel or taste the powder medication during administration; however, do not repeat the dose if it is not felt.
Do NOT use a spacer with the Diskus inhaler.
After administration, instruct patient to rinse mouth with water to minimize dry mouth.
To avoid the spread of infection, the device should not be used by more than one person. 
Storage: The Diskus device and mouthpiece should be kept dry; do not wash. Discard the Diskus device 6 weeks after opening the foil pouch or when the counter reads “0” (after all blisters have been used), whichever comes first.

Severe

laryngospasm / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known
asthma-related death / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
angioedema / Rapid / Incidence not known

Moderate

tracheitis / Delayed / 3.0-7.0
hypertension / Early / 4.0-4.0
migraine / Early / 1.0
bone pain / Delayed / 1.0
candidiasis / Delayed / 1.0
elevated hepatic enzymes / Delayed / 1.0
wheezing / Rapid / Incidence not known
hypokalemia / Delayed / Incidence not known
hypotension / Rapid / Incidence not known
QT prolongation / Rapid / Incidence not known
sinus tachycardia / Rapid / Incidence not known
palpitations / Early / Incidence not known
angina / Early / Incidence not known
contact dermatitis / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known

Mild

headache / Early / 13.0-17.0
musculoskeletal pain / Early / 12.0-12.0
nasal congestion / Early / 4.0-9.0
influenza / Delayed / 5.0-5.0
rhinitis / Early / 4.0-5.0
dizziness / Early / 4.0-4.0
rash / Early / 4.0-4.0
urticaria / Rapid / 3.0-3.0
nausea / Early / 3.0-3.0
vomiting / Early / 3.0-3.0
muscle cramps / Delayed / 3.0-3.0
pharyngitis / Delayed / 3.0
sinusitis / Delayed / 3.0
infection / Delayed / 3.0
cough / Delayed / 3.0
anxiety / Delayed / 1.0
dyspepsia / Early / 1.0
arthralgia / Delayed / 1.0
xerostomia / Early / 1.0
dental pain / Delayed / 1.0
fatigue / Early / Incidence not known
insomnia / Early / Incidence not known
paresthesias / Delayed / Incidence not known
tremor / Early / Incidence not known
malaise / Early / Incidence not known

Acute bronchospasm, asthma-related death, status asthmaticus

Due to its relatively prolonged onset of action, salmeterol is contraindicated for use in patients with an acute asthma attack or status asthmaticus. Salmeterol should not be initiated in patients with deterioration of asthma or used for episodes of acute bronchospasm. It is crucial to properly educate patients and prescribe an inhaled, short-acting beta-agonist (SABA), such as albuterol, for rescue treatment. If wheezing worsens and cannot be relieved during an acute asthma attack, patients should be instructed to seek immediate medical attention.[28467] Salmeterol is not a substitute for inhaled corticosteroid therapy (ICS) or oral corticosteroid therapy; corticosteroids should not be stopped or reduced when salmeterol is initiated. Subsequent changes to any preexisting corticosteroid regimen, such as a dose reduction, should only be made following a thorough clinical evaluation. Salmeterol, as monotherapy for asthma, increases the risk for asthma-related death.[28467] Available data from controlled clinical trials also suggest that LABA monotherapy for asthma increases the risk of asthma-related hospitalization in pediatric and adolescent patients.[28467] When LABA are used in fixed-dose combination with an ICS to control lung inflammation, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone.[28467] The Salmeterol Multicenter Asthma Research Trial (SMART) was a large 28-week placebo-controlled U.S. trial comparing the safety of salmeterol inhalation aerosol) with placebo, each added to usual asthma therapy, that showed an increase in asthma-related deaths in subjects receiving salmeterol. Given the similar basic mechanisms of action of long-acting beta-2 agonists (LABAs), the findings seen in the SMART trial are considered a class effect. A 16-week clinical trial performed in the United Kingdom, the Salmeterol Nationwide Surveillance (SNS) trial, showed results similar to the SMART trial. In the SNS trial, the rate of asthma-related death was numerically, though not statistically significantly, greater in subjects with asthma treated with salmeterol (42 mcg twice daily) than those treated with albuterol (180 mcg 4 times daily) added to usual asthma therapy. The SNS and SMART trials enrolled subjects only with asthma.[28467] [41230] There are no data to suggest an increased risk of death with use of LABAs in patients with COPD.[28467] In December 2017, the FDA announced that there is no increase in risk of serious asthma outcomes with long-acting beta-agonists (LABAs) when used in combination with an inhaled corticosteroid (ICS); the results of all trials showed that the use of LABA in combination with ICS does not significantly increase the risk of serious asthma outcomes compared to ICS alone. The trials showed that ICS/LABA combination medicines were more effective in decreasing asthma attacks (e.g., the need to use oral corticosteroids) compared to ICS alone. Three trials were conducted in patients 12 years and older and the fourth trial included pediatric patients 4 to 11 years.[62717]
 

Serevent Diskus

Rx

Orally inhaled long-acting beta-2 agonist (LABA); given twice daily
Used in adult and pediatric patients 4 years and older for add-on asthma maintenance therapy to an asthma controller medication and for exercise-induced bronchospasm (EIB); also used for maintenance treatment of COPD in adults
LABA monotherapy for asthma is contraindicated due to an increased risk for asthma-related death

For asthma maintenance treatment. Oral Inhalation dosage (inhalation powder; e.g., Serevent Diskus) Adults

50 mcg (1 oral inhalation of 50 mcg/actuation) twice daily, in the morning and evening, approximately 12 hours apart, is the recommended and max dose (Max: 100 mcg/day). Salmeterol monotherapy for asthma is contraindicated; use concurrently with a controller medication, such as an inhaled corticosteroid. Use of a fixed-dose combination product containing both salmeterol and an inhaled corticosteroid (e.g., Advair) is preferred to this product.

Children and Adolescents 4 to 17 years

50 mcg (1 oral inhalation of 50 mcg/actuation) twice daily, in the morning and evening, approximately 12 hours apart, is the recommended and max dose (Max: 100 mcg/day). Salmeterol monotherapy for asthma is contraindicated; use concurrently with a controller medication, such as an inhaled corticosteroid. Use of a fixed-dose combination product containing both salmeterol and an inhaled corticosteroid (e.g., Advair) is preferred to this product.

For exercise-induced bronchospasm prophylaxis. Oral Inhalation dosage (inhalation powder; e.g., Serevent Diskus) Adults

50 mcg (1 oral inhalation of 50 mcg/actuation) at least 30 minutes before exercise. Protection lasts up to 9 hours in adults, although duration may decrease with regular use. Do not use any additional doses within 12 hours after administering initial dose. Also, do not use an additional dose to prevent exercise-induced bronchospasm (EIB) in patients receiving salmeterol twice daily for asthma maintenance therapy.

Children and Adolescents 4 years and older

50 mcg (1 oral inhalation of 50 mcg/actuation) at least 30 minutes before exercise. Protection lasts up to 12 hours in children and 9 hours in adolescents, although duration may decrease with regular use. Do not use any additional doses within 12 hours after administering initial dose. Also, do not use an additional dose to prevent exercise-induced bronchospasm (EIB) in patients receiving salmeterol twice daily for asthma maintenance therapy.

For the maintenance treatment of chronic obstructive pulmonary disease (COPD) (e.g., chronic bronchitis or emphysema). Oral Inhalation dosage (inhalation powder; e.g., Serevent Diskus) Adults

50 mcg (1 oral inhalation of 50 mcg/actuation) twice daily, morning and evening, approximately 12 hours apart is the recommended and max dosage. Not indicated to treat acute exacerbations of COPD and should not be used for the relief of acute bronchospasm; use a short-acting beta-2 agonist (SABA) for rescue therapy. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for COPD, salmeterol and other LABAs may be used as initial monotherapy in patients in Groups A and B. In Group C patients, long-acting muscarinic antagonists (LAMAs) are preferred as initial therapy over LABAs due to effectiveness in preventing exacerbations. In Group D patients, LABAs are used as initial therapy in combination with inhaled corticosteroids (ICS) or LAMAs. At follow-up, if the patient is still experiencing dyspnea, consider switching inhaler device and investigate for other causes of dyspnea. If the patient has exacerbations, consider triple therapy with a LAMA, a LABA, and ICS.

For altitude sickness prophylaxis†, specifically prevention of high altitude pulmonary edema†. Oral inhalation dosage Adults

125 mcg by oral inhalation every 12 hours starting the day before ascent and continuing for 5 days after reaching the target altitude or until descent is initiated as an adjunct to nifedipine. Prophylactic medications should only be considered for individuals with a prior history of high altitude pulmonary edema.

†Indicates off-label use

Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available. Salmeterol is predominately metabolized in the liver; hepatic impairment may lead to drug accumulation. Close monitoring is recommended.

Renal Impairment

No dosage adjustments are needed.

Acebutolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Acetaminophen; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Caution and close observation should also be used when salmeterol 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 also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Caution and close observation should also be used when salmeterol 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 also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Acetaminophen; Phenylephrine: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Acetaminophen; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Aclidinium; Formoterol: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists.
Acrivastine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Adagrasib: (Major) Avoid concomitant use of salmeterol with adagrasib. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Aliskiren; Hydrochlorothiazide, HCTZ: (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.
Amiloride; Hydrochlorothiazide, HCTZ: (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.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (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.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid concomitant use of salmeterol with clarithromycin. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Amphetamine: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine; dextroamphetamine and salmeterol use. Concomitant use may potentiate sympathetic effects.
Amphetamine; Dextroamphetamine Salts: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine; dextroamphetamine and salmeterol use. Concomitant use may potentiate sympathetic effects.
Amphetamine; Dextroamphetamine: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine; dextroamphetamine and salmeterol use. Concomitant use may potentiate sympathetic effects.
Articaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and salmeterol use. Concomitant use may potentiate sympathetic effects.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Aspirin, ASA; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Atazanavir: (Major) Avoid concomitant use of salmeterol with atazanavir. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Atazanavir; Cobicistat: (Major) Avoid concomitant use of salmeterol with atazanavir. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose. (Major) Avoid concomitant use of salmeterol with cobicistat. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Atenolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Atenolol; Chlorthalidone: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. (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.
Azilsartan; Chlorthalidone: (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.
Benazepril; Hydrochlorothiazide, HCTZ: (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.
Benzphetamine: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Beta-adrenergic blockers: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Betaxolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Bisoprolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. (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.
Brimonidine; Timolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Caution and close observation should also be used when salmeterol 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 also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Brompheniramine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Budesonide; Formoterol: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists.
Budesonide; Glycopyrrolate; Formoterol: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists.
Bumetanide: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
Bupivacaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and salmeterol use. Concomitant use may potentiate sympathetic effects.
Butalbital; Acetaminophen; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Butalbital; Aspirin; 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.
Candesartan; Hydrochlorothiazide, HCTZ: (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.
Captopril; Hydrochlorothiazide, HCTZ: (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.
Carteolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Carvedilol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Ceritinib: (Major) Avoid concomitant use of salmeterol with ceritinib. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Cetirizine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Chloramphenicol: (Major) Avoid concomitant use of salmeterol with chloramphenicol. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Chlorothiazide: (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.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Chlorpheniramine; Phenylephrine: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Chlorpheniramine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Chlorthalidone: (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.
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.
Clarithromycin: (Major) Avoid concomitant use of salmeterol with clarithromycin. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Cobicistat: (Major) Avoid concomitant use of salmeterol with cobicistat. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Cocaine: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Codeine; Phenylephrine; Promethazine: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Darunavir: (Major) Avoid concomitant use of salmeterol with darunavir. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Darunavir; Cobicistat: (Major) Avoid concomitant use of salmeterol with cobicistat. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose. (Major) Avoid concomitant use of salmeterol with darunavir. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid concomitant use of salmeterol with cobicistat. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose. (Major) Avoid concomitant use of salmeterol with darunavir. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Delavirdine: (Major) Avoid concomitant use of salmeterol with delavirdine. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and delavirdine is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Desloratadine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Dextroamphetamine: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine; dextroamphetamine and salmeterol use. Concomitant use may potentiate sympathetic effects.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Caution and close observation should also be used when salmeterol 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 also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Diethylpropion: (Moderate) Caution and close observation should also be used when salmeterol 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 also be used when salmeterol 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 also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Dopamine: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Dorzolamide; Timolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concomitant use of salmeterol with cobicistat. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of salmeterol with cobicistat. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Enalapril; Hydrochlorothiazide, HCTZ: (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.
Ephedrine: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Ephedrine; Guaifenesin: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and salmeterol use. Concomitant use may potentiate sympathetic effects.
Eprosartan; Hydrochlorothiazide, HCTZ: (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.
Ergotamine; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Esmolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Ethacrynic Acid: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
Fexofenadine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Formoterol: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists.
Formoterol; Mometasone: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists.
Fosamprenavir: (Major) Avoid concomitant use of salmeterol with fosamprenavir. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Fosinopril; Hydrochlorothiazide, HCTZ: (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.
Furosemide: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
Glycopyrrolate; Formoterol: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists.
Grapefruit juice: (Major) Advise patients to avoid grapefruit and grapefruit juice during salmeterol treatment due to the risk of increased salmeterol exposure and adverse reactions. Salmeterol is a CYP3A substrate and grapefruit juice is a strong CYP3A inhibitor.
Guaifenesin; Phenylephrine: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Guaifenesin; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Hydrochlorothiazide, HCTZ: (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.
Hydrochlorothiazide, HCTZ; Moexipril: (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.
Hydrocodone; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Ibuprofen; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Idelalisib: (Major) Avoid concomitant use of salmeterol with idelalisib. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Indacaterol; Glycopyrrolate: (Major) Indacaterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist, such as salmeterol for any reason, as overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with an inhaled short-acting beta-2 agonist (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking indacaterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if indacaterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual.
Indinavir: (Major) Avoid concomitant use of salmeterol with indinavir. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and indinavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Irbesartan; Hydrochlorothiazide, HCTZ: (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.
Isocarboxazid: (Moderate) Use beta-agonists with caution in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with MAOIs because the action of beta-agonists on the cardiovascular system may be potentiated.
Isoproterenol: (Major) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Itraconazole: (Major) Avoid concomitant use of salmeterol with itraconazole. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and itraconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Ketoconazole: (Major) Avoid concomitant use of salmeterol with ketoconazole. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Coadministration with ketoconazole increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Labetalol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of salmeterol with clarithromycin. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Levobunolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Levoketoconazole: (Major) Avoid concomitant use of salmeterol with ketoconazole. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Coadministration with ketoconazole increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Levothyroxine: (Moderate) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
Levothyroxine; Liothyronine (Porcine): (Moderate) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
Levothyroxine; Liothyronine (Synthetic): (Moderate) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
Lidocaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and salmeterol use. Concomitant use may potentiate sympathetic effects.
Linezolid: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
Liothyronine: (Moderate) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
Lisdexamfetamine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and lisdexamfetamine use. Concomitant use may potentiate sympathetic effects.
Lisinopril; Hydrochlorothiazide, HCTZ: (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.
Lonafarnib: (Major) Avoid concomitant use of salmeterol with lonafarnib. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and lonafarnib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Loop diuretics: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
Lopinavir; Ritonavir: (Major) Avoid concomitant use of salmeterol with ritonavir. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Loratadine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Losartan; Hydrochlorothiazide, HCTZ: (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.
Methacholine: (Major) Discontinue use of salmeterol 36 hours before a methacholine challenge test. Beta-agonists inhibit the airway response to methacholine.
Methamphetamine: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Metolazone: (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.
Metoprolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. (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.
Midodrine: (Moderate) Caution and close observation should be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effe

cts.
Mifepristone: (Major) Avoid concomitant use of salmeterol with mifepristone. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Monoamine oxidase inhibitors: (Moderate) Use beta-agonists with caution in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with MAOIs because the action of beta-agonists on the cardiovascular system may be potentiated.
Nadolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Naproxen; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Nebivolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Nebivolol; Valsartan: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Nefazodone: (Major) Avoid concomitant use of salmeterol with nefazodone. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and nefazodone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Nelfinavir: (Major) Avoid concomitant use of salmeterol with nelfinavir. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and nelfinavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Nirmatrelvir; Ritonavir: (Major) Avoid concomitant use of salmeterol with ritonavir. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose. (Major) Consider temporary discontinuation of salmeterol during treatment with ritonavir-boosted nirmatrelvir and for at least 2 to 3 days after treatment completion; if not feasible, consider alternative COVID-19 therapy. Coadministration may increase salmeterol exposure resulting in increased toxicity, including QT prolongation, palpitations, and sinus tachycardia. Salmeterol is a CYP3A substrate and nirmatrelvir is a CYP3A inhibitor.
Norepinephrine: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (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.
Olmesartan; Hydrochlorothiazide, HCTZ: (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.
Phendimetrazine: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Phenelzine: (Moderate) Use beta-agonists with caution in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with MAOIs because the action of beta-agonists on the cardiovascular system may be potentiated.
Phentermine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and phentermine use. Concomitant use may potentiate sympathetic effects.
Phentermine; Topiramate: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and phentermine use. Concomitant use may potentiate sympathetic effects.
Phenylephrine: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Pindolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Posaconazole: (Major) Avoid concomitant use of salmeterol with posaconazole. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Prilocaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and salmeterol use. Concomitant use may potentiate sympathetic effects.
Procarbazine: (Major) Procarbazine has MAOI activity and the cardiovascular effects of beta-2 agonists may be potentiated by concomitant use of MAOIs. Although no data are available, procarbazine may interact similarly. Close observation for such effects is prudent, particularly if beta-agonists are administered within two weeks of stopping the MAOI.
Promethazine; Phenylephrine: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Propranolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Pseudoephedrine; Triprolidine: (Moderate) Monitor blood pressure and heart rate during concomitant salmeterol and pseudoephedrine use. Concomitant use may potentiate sympathetic effects.
Quinapril; Hydrochlorothiazide, HCTZ: (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.
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.
Ribociclib: (Major) Avoid concomitant use of salmeterol with ribociclib. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Ribociclib; Letrozole: (Major) Avoid concomitant use of salmeterol with ribociclib. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Ritonavir: (Major) Avoid concomitant use of salmeterol with ritonavir. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Saquinavir: (Major) Avoid concomitant use of salmeterol with saquinavir. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and saquinavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Spironolactone; Hydrochlorothiazide, HCTZ: (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.
Telmisartan; Hydrochlorothiazide, HCTZ: (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.
Theophylline, Aminophylline: (Moderate) Beta-agonists are commonly used in conjunction with aminophylline or theophylline therapy. Concomitant use can cause additive CNS stimulation; some patients may experience tremor or nervousness with combined use. More serious effects are rare, but may result in additive cardiovascular effects such as increased blood pressure and heart rate. Methylxanthine derivatives, ((e.g., theophylline and aminophylline) may rarely aggravate the hypokalemic effect seen with beta-agonists. Consider checking potassium levels if clinically indicated. (Moderate) Beta-agonists are commonly used in conjunction with aminophylline or theophylline therapy. Concomitant use can cause additive CNS stimulation; some patients may experience tremor or nervousness with combined use. More serious effects are rare, but may result in additive cardiovascular effects such as increased blood pressure and heart rate. Methylxanthine derivatives, (e.g., theophylline, aminophylline) may rarely aggravate the hypokalemic effect seen with beta-agonists. Consider checking potassium levels if clinically indicated.
Thiazide diuretics: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
Thyroid hormones: (Moderate) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
Timolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Tipranavir: (Major) Avoid concomitant use of salmeterol with tipranavir. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and tipranavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Torsemide: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
Tranylcypromine: (Moderate) Use beta-agonists with caution in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with MAOIs because the action of beta-agonists on the cardiovascular system may be potentiated.
Triamterene; Hydrochlorothiazide, HCTZ: (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.
Tucatinib: (Major) Avoid concomitant use of salmeterol with tucatinib. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and tucatinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Valsartan; Hydrochlorothiazide, HCTZ: (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.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of salmeterol with clarithromycin. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Voriconazole: (Major) Avoid concomitant use of salmeterol with voriconazole. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and voriconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.

Serevent Diskus Respiratory (Inhalation) Inhalant: 1actuation, 50mcg

Adults

100 mcg/day oral inhalation powder.

Geriatric

100 mcg/day oral inhalation powder.

Adolescents

100 mcg/day oral inhalation powder.

Children

4 years or older: 100 mcg/day oral inhalation powder.
Less than 4 years: Safety and efficacy have not been established.

Mechanism of Action: Salmeterol is an agonist at beta-2 receptors. These receptors are present in large numbers in the lungs and are located on bronchiolar smooth muscle. Stimulation of beta-2 receptors in the lung causes relaxation of bronchial smooth muscle, which produces bronchodilation and a resultant increase in bronchial airflow. These effects are believed to be mediated, in part, by increased activity of adenyl cyclase, an intracellular enzyme responsible for the formation of cyclic-3',5'-adenosine monophosphate (cAMP).Salmeterol can inhibit the bronchoconstriction produced by histamine, methacholine, and exercise. In addition, salmeterol appears to inhibit the late phase of allergen-induced bronchoconstriction, which usually appears after the bronchodilating effects of the shorter-acting agents have resolved.The extended action of salmeterol is due to its long, lipophilic side chain. This side chain appears to bind to an exosite present only near beta-2 receptors. Binding to this exosite allows the active portion of the molecule to remain at the receptor site and continually engage and disengage with the receptor, therefore providing a long duration of action. Also, exosite binding contributes to salmeterol's inhibition of late-phase responses to allergens.

Salmeterol is administered by oral inhalation. Protein binding of salmeterol is approximately 94—98% of the serum concentration. Extensive metabolism occurs via hydroxylation. In addition, in vitro data indicate that salmeterol also undergoes aliphatic oxidation through hepatic CYP3A4, which results in the formation of alpha-hydroxysalmeterol. Use of a strong inhibitor of CYP3A4, ketoconazole, in in vitro study has been shown to inhibit metabolism and result in significantly increased salmeterol systemic exposure. The elimination half-life of orally administered salmeterol was determined as approximately 5 hours. Excretion is primarily in the feces. No significant amount of unchanged salmeterol has been detected in either urine or feces.

Inhalation Route

Following inhalation, a minimal amount of salmeterol is systemically absorbed to produce plasma concentrations of 0.1—0.2 mcg/L in healthy subjects. The onset of therapeutic effects, as measured by a 15% improvement in forced expiratory flow in one second (FEV1), occurs in approximately 14 minutes with salmeterol aerosol compared to 7 minutes with albuterol. Peak effects of salmeterol aerosol are observed 3—4 hours following oral inhalation. The median time to therapeutic onset with salmeterol inhalational powder is 30—50 minutes, with maximal increases in FEV1 occurring within 2 hours. Compared to albuterol, salmeterol produces similar mean peak increases in peak expiratory flow rates (PEFR) and FEV1. With salmeterol, however, the bronchodilator effects persisted at greater than half of the maximum effect for 12 hours, whereas with albuterol, PEFR and FEV1 returned to baseline within 6 hours.

Pregnancy

There is no information regarding the presence of salmeterol in human milk, the effects on the breastfed child, or the effects on milk production. Salmeterol has been shown to be excreted in the milk of rats; however, data describing the use of salmeterol during human lactation are unavailable. Plasma concentrations of salmeterol after inhaled therapeutic doses are very low. Most inhaled bronchodilators are considered acceptable for use during the postpartum period and breast-feeding because of the low bioavailability and maternal serum levels after use. According to the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group, long-acting beta-2 agonists (LABAs) in combination with inhaled corticosteroids (ICSs) are one of the preferred treatment options for the long-term management of moderate persistent asthma during pregnancy and lactation. Although a preferred LABA is not recommended, the NAEPP guideline states that more experience is available with salmeterol. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.