Formoterol is an inhaled long-acting beta-2 receptor agonist (LABA) given twice daily via nebulizer. Formoterol is indicated for the maintenance treatment of airflow obstruction associated with chronic obstructive pulmonary disease (COPD). Due to the delayed onset of effect, the FDA-approved label notes that formoterol should not be used for relief of acute bronchospasm. Formoterol significantly improves FEV1, lung volume, dyspnea, health-related quality of life, and exacerbation rates in COPD patients, but does not affect mortality or the rate of lung function decline. According to guidelines, LABAs may be used as initial monotherapy in COPD patients in group A. A long-acting bronchodilator is the preferred choice except in patients with very occasional breathlessness. In patients with stable disease, long-acting muscarinic antagonists (LAMAs) have a greater effect on exacerbation reduction compared to LABAs and decrease hospitalizations. In COPD patients in Group B and Group E, LABAs are used as initial therapy in combination with LAMAs. At follow-up, if the patient is still experiencing dyspnea, consider switching inhaler device, implement or escalate non-pharmacologic treatment(s), and investigate for other causes of dyspnea. If the patient has exacerbations, consider triple therapy with a LAMA, a LABA, and an inhaled corticosteroid (ICS). Formoterol has been used clinically for the maintenance treatment of asthma but should not be used alone; there are combination formoterol with inhaled corticosteroids (ICS) that are part of preferred regimens for asthma management in selected patients with persistent asthma. The use of LABAs alone to treat asthma without an ICS to treat lung inflammation is associated with an increased risk of asthma-related death; therefore, LABAs are contraindicated for use in patients with asthma without the concurrent use of an asthma controller medication (i.e., an ICS).
General Administration Information
For storage information, see specific product information within the How Supplied section.
Route-Specific Administration
Inhalation Administration
Oral Inhalation Administration
Inhalation solution for nebulization (Perforomist):
-For oral inhalation via nebulization only.
-Dilution of the solution is not necessary prior to administration.
-Open the foil pouch to remove the dose immediately prior to use. Store unused doses in the foil pouch until time of use.
-Only administer via a standard jet nebulizer connected to an air compressor with adequate airflow and a face mask or mouthpiece. Safety and efficacy of using this product with non-compressor based nebulizer systems have not been established.
-The approximate nebulization time for a single dose is 9 minutes; however, this may vary depending upon the nebulizer system used.
-Discard contents of any partially used container. Discard the container and top immediately after use because it is a choking hazard to infants.
-Compatibility, safety, and efficacy with concurrently administered nebulized drugs have not been established.
Formoterol, like other beta2-agonists and sympathomimetic amines, can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate (sinus tachycardia), systolic or diastolic blood pressure (hypertension), and/or symptoms or cardiac arrhythmias, such as supraventricular tachycardia (SVT) and extrasystoles (palpitations). If such effects occur, formoterol may need to be discontinued. Beta-agonists have been reported to produce ECG changes, such as flattening of the T wave, QT prolongation, and ST segment depression; the clinical significance of these findings is unknown. Overall, the frequency of all cardiovascular (CV) events in the clinical studies of formoterol (inhaler and nebulizer solution) was low and comparable to placebo. Patients with pre-existing cardiac disease and/or COPD may be more at risk for potential CV effects; patients with significant concurrent cardiac and other medical diseases were excluded from the pre-approval trials with formoterol nebulizer solution. There were no frequently occurring specific CV adverse events for formoterol inhalation solution for nebulization (frequency 1% or more and greater than placebo). Chest pain (unspecified) occurred in 1.9% to 3.2% of patients treated with formoterol inhaler (Foradil Aerolizer) vs. 1.3% to 2.1% receiving placebo during clinical studies. Continuous electrocardiographic (ECG) monitoring was performed in an 8-week, randomized, double-blind, placebo controlled trial of 204 adult COPD patients (pre-existing CV conditions not stated) treated with formoterol inhaler (Foradil Aerolizer) 12 mcg twice daily or placebo. Holter monitoring was used to evaluate predefined pro-arrhythmic events. Non-sustained ventricular tachycardia occurred in two (2.2%) of the formoterol treated patients vs. 0% in the placebo group. An increase in ventricular premature beats (VPB) occurred in 3.3% of formoterol treated patients vs. 1.9% in the placebo group. There were no events of sustained of ventricular tachycardia, ventricular flutter or fibrillation, or symptomatic runs of VPB. One patient in the formoterol group had a serious adverse event of atrial flutter. In general, formoterol's cardiac adverse event profile is similar to other comparable long-acting beta agonist agents. During postmarketing experience, angina pectoris, cardiac arrhythmias (e.g., atrial fibrillation, ventricular extrasystoles, and tachyarrhythmias), QT interval prolonged on ECG, increased blood pressure, including hypertension have been reported with use of fluticasone inhaler (Foradil Aerolizer).
Formoterol is well tolerated at normal therapeutic doses. Dizziness (1.6% to 2.4%), dysphonia (1%), insomnia (1.5% to 2.4%), tremor (1.9%), and muscle cramps (1.7%) were reported in clinical trials of inhaled formoterol. Additional adverse events experienced with other beta-agonists that may occur with formoterol include hoarseness, nervousness, headache, fatigue, and malaise.
Rarely, anaphylactoid reactions with severe hypotension or angioedema have been reported with formoterol. Urticaria, pruritus (1.5%), and rash (unspecified) (1.1%) have also been reported. Reports of photosensitivity were considered possibly related to formoterol use in 3 patients in an observational cohort study.
Gastrointestinal adverse events reported in patients receiving formoterol in clinical trials at a greater frequency than patients receiving placebo include nausea (4.9%), vomiting (2.4%), xerostomia (1.2-3.3%), and diarrhea (4.9%). Abdominal pain, nausea, gastroenteritis, and dyspepsia have been reported more frequently in children 5-12 years of age receiving formoterol in clinical trials than in adults.
Tolerance to formoterol aerosol has been reported in several clinical studies with a dose of 24 mcg two times a day (twice the recommended dose). Tolerance was observed as evidenced by diminished forced expiratory volume in one second (FEV1) and loss of the bronchoprotective effect at the end of the 12-hour dose period. Clinically significant tolerance was not observed with the 12 mcg twice daily dose of formoterol in combination with budesonide in a 12-month study. No evidence of hyper-responsiveness (worsening of symptoms) was reported after discontinuation of formoterol in an observational cohort study.
Paresthesias that reoccurred upon formoterol rechallenge and were temporally related to formoterol use have been reported. Paresthesias appear to be infrequent ADRs but have resulted in discontinuation of treatment in several patients.
Formoterol, like other inhaled beta-agonists, can produce life-threatening paradoxical bronchospasm. In the event of a paradoxical bronchospasm, discontinue formoterol immediately and initiate an alternative therapy. Infectious or respiratory adverse events reported in patients receiving formoterol in clinical trials at a greater frequency than patients receiving placebo include increased bronchial secretions (sputum production) (1.5%), viral infection (17.2%), upper respiratory tract infection (7.4%), bronchitis (4.6%), pharyngitis (3.3-3.5%), sinusitis (2.7%), chest infection (2.7%), fever (2.2%), dyspnea (2.1%), and tonsillitis (1.2%). Infectious or respiratory adverse events reported in asthmatic children 5-12 years of age receiving formoterol aerosol in clinical trials include rhinitis, tonsillitis, and viral infection. In a clinical trial of asthmatic children 5-12 years of age receiving formoterol aerosol, serious asthma exacerbations occurred more often in patients receiving formoterol at doses of 24 mcg/day (4.7%) and 48 mcg/day (6.4%) compared to patients receiving placebo (0%). Serious asthma exacerbations also occurred more frequently in adult and adolescent patients receiving formoterol aerosol 48 mcg/day compared to placebo, but not in patients receiving 24 mcg/day. In general, formoterol aerosol is well tolerated at a dose of 12 mcg twice a day.
An increase in the need for rescue inhaler use and/or worsening wheezing may occur during therapy with formoterol and are symptoms of a deterioration of the underlying respiratory condition, a potentially life-threatening situation. Advise patients not to exceed recommended doses of this medicine, but instead, seek immediate medical attention if such symptoms occur. When long-acting beta agonists (LABAs) are used in fixed-dose combination with inhaled corticosteroids (ICS), 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. The use of a LABA as asthma monotherapy, without an ICS, is associated with an increased risk of asthma-related death. Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA monotherapy. In most cases, serious acute respiratory events have occurred in patients with severe asthma and/or in patients in whom asthma has been acutely deteriorating, but such events have also occurred in patients with less severe asthma. These findings pertain only to patients who have asthma.
Beta-agonist medications such as formoterol may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease in serum potassium is usually transient, not requiring supplementation. Clinically significant changes in blood glucose and/or serum potassium were infrequent during clinical studies with long-term administration of formoterol inhaler or nebulization solution at the recommended doses. Both hypokalemia and hyperglycemia have been reported with postmarketing experience.
Currently marketed formoterol products are not FDA-approved for the treatment of asthma. All long-acting beta agonists (LABAs) are contraindicated for monotherapy treatment of asthma and, in patients with asthma, must be used with an asthma controller medication (i.e., inhaled corticosteroid).
Paradoxical bronchospasm can occur after treatment with formoterol and can be life-threatening. If this occurs, formoterol should be discontinued immediately and supportive care provided as necessary.
LABAs, such as formoterol, increase the risk of asthma-related death when used without ICSs; this is considered a class effect. No study adequate to determine whether the rate of asthma-related death is increased in patients treated with formoterol has been conducted. LABAs should only be used in conjunction with ICSs for asthma; studies have found that the combined use of LABA/ICS does not increase the risk for serious asthma-related events. Formoterol should not be used for the relief of acute symptoms (i.e., as rescue therapy for the treatment of acute bronchospasm) of COPD and extra doses should not be used for that purpose. Acute symptoms should be treated with an inhaled short-acting beta-2 agonist (SABA). Formoterol should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD. Available data do not suggest an increased risk of death with use of LABA in patients with COPD; however, the drug has not been studied in patients with acutely deteriorating COPD. It is crucial to inform patients of this and prescribe an inhaled SABA (e.g., albuterol), for rescue treatment of an acute attack as well as to warn them that increasing inhaled SABA use is a signal of deteriorating disease. Loss of symptom control with formoterol is also a marker of deterioration of disease; in this setting a re-evaluation of the patient and the COPD treatment regimen should be undertaken at once. Increasing the daily dose of formoterol beyond the recommended dose is not appropriate in this situation. Furthermore, patients should not use formoterol more often than recommended, at higher doses than recommended, or in conjunction with other LABAs as this would be considered duplicative therapy and may lead to additive untoward effects. Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma.
Formoterol should be used cautiously in patients with hyperthyroidism (thyrotoxicosis), diabetes mellitus, history of seizure disorder, pheochromocytoma, or other unusual responsiveness to other sympathomimetic amines. Beta-agonists may cause transient hyperglycemia. Exacerbation of diabetes mellitus has occurred when short-acting beta-2 agonists (e.g., albuterol) have been administered systemically. During long-term studies of formoterol solution for nebulization, clinically significant changes in blood glucose occurred in some patients.
Formoterol, like other beta2-agonists and sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency (coronary artery disease), cardiac arrhythmias, and hypertension. Formoterol can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, and cardiac arrhythmias, such as supraventricular tachycardia and extrasystoles. If such effects occur, formoterol may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiographic changes, such as flattening of the T wave, QT prolongation, and ST segment depression, although the clinical significance of these findings is unknown. Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Beta-adrenergic agonist therapies like formoterol may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease in serum potassium is usually transient, not requiring supplementation.
The limited data with formoterol use during human pregnancy are not sufficient to inform of drug-associated risk of adverse developmental outcomes. Use during pregnancy only if the potential benefit justifies the potential risk. In animal reproduction studies, oral administration of formoterol fumarate to pregnant rats and rabbits caused increased fetal malformations (rats and rabbits), decreased fetal weight (rats), and increased neonatal mortality (rats) following administration of doses that produced exposures approximately 730 to 29,000 times the maximum recommended human dose (MRHD) on a mg/m2 or AUC basis. These adverse effects generally occurred at large multiples of the MRHD when formoterol fumarate was administered by the oral route to achieve high systemic exposures. No effects were observed in a study with rats that received formoterol fumarate by the inhalation route at an exposure approximately 300 times the MRHD. It is known that improved maternal and perinatal outcomes are achieved with optimal control of asthma during pregnancy. Large studies of women with asthma have confirmed the lack of relationship between the use of inhaled beta-2 agonists and adverse maternal or fetal outcomes; however, less data are available for long-acting beta agonists (LABAs) such as formoterol vs. short-acting beta agonists (SABAs). However, most inhaled beta-2 agonists are considered acceptable for use during pregnancy because of the low bioavailability and maternal serum levels after use. According to the 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group, long-acting beta-agonists (LABAs), in combination with inhaled corticosteroids (ICS), are one of the preferred treatment options for the long-term control of moderate asthma during pregnancy and lactation. Although a preferred LABA is not recommended, the guideline states that more experience is available with salmeterol. Beta-2 agonists can interfere with uterine contractility during labor; do not use formoterol during labor unless the benefits outweigh the risks.
There are no well-controlled human studies of the use of formoterol in women who are breast-feeding. It is not known whether formoterol is excreted in human milk. Formoterol was excreted in milk in reproductive studies in rats. The amount of radioactive formoterol was less than 2% of that in the maternal plasma. However, 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 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group, long-acting beta-agonists (LABA), in combination with inhaled corticosteroids, are one of the preferred treatment options for the long-term control of moderate persistent asthma during pregnancy and lactation. The NAEPP suggests that LABA may be used during pregnancy and lactation because the toxicologic and pharmacologic profile is similar to that of short-acting beta-2 agonists (SABAs), for which a significant amount of data is available. Although a preferred LABA is not recommended, the guideline states that more experience is available with salmeterol. Of note, the inclusion of LABA as an option for patients with moderate asthma was based off of efficacy data, and no safety data in pregnant or lactating women were available at the time of the report. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Beta-2 adrenergic agonists such as formoterol should be administered with extreme caution to patients being treated with monoamine oxidase inhibitor therapy (MAOI therapy). The action of adrenergic agonists on the cardiovascular system may be potentiated by these agents.
No overall differences in safety or effectiveness were observed between geriatric subjects and younger subjects in the various studies of formoterol for the treatment of COPD. During asthma studies, a slightly higher frequency of chest infection was reported in the older adults 75 years and older, although a causal relationship with formoterol has not been established. Other reported clinical experience has not identified differences in responses between geriatric and younger adults, but greater sensitivity of some older individuals cannot be ruled out.
Safety and efficacy of formoterol have not been established in children and infants under the age of 5 years, and currently marketed formoterol products are not FDA-approved for the treatment of pediatric patients. Available data from clinical trials suggest that LABAs, such as formoterol, increase the risk of asthma-related hospitalization in children and adolescents.
Immediate hypersensitivity reactions may occur after administration of formoterol, as demonstrated by cases of anaphylactic reactions, urticaria, angioedema, rash, and bronchospasm. If such reactions occur, stop use of the product and treat the allergy as per standard of care. Alternative treatment should be considered. Previously marketed formoterol inhalation powders contained lactose as a carrier; the product information carried a warning that patients with a severe milk protein hypersensitivity may experience an allergic reaction to these products.
For the maintenance treatment of chronic obstructive pulmonary disease (COPD) (e.g., chronic bronchitis or emphysema):
Nebulized Inhalation dosage (solution for nebulization; e.g., Perforomist):
Adults: 20 mcg (one 2 mL unit) via nebulizer twice daily, in the morning and evening. Max: 40 mcg/day. Administer with a standard jet nebulizer connected to an air compressor. Safety and efficacy of use with non-compressor based nebulizer systems have not been established. 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 guidelines, formoterol and other LABAs may be used as initial monotherapy in COPD patients in group A. A long-acting bronchodilator is the preferred choice except in patients with very occasional breathlessness. In patients with stable disease, long-acting muscarinic antagonists (LAMAs) have a greater effect on exacerbation reduction compared to LABAs and decrease hospitalizations. In patients in Group B and Group E, LABAs are used as initial therapy in combination with LAMAs. At follow-up, if the patient is still experiencing dyspnea, consider switching inhaler device, implement or escalate non-pharmacologic treatment(s), and investigate for other causes of dyspnea. If the patient has exacerbations, consider triple therapy with a LAMA, a LABA, and an inhaled corticosteroid (ICS).
Maximum Dosage Limits:
-Adults
40 mcg/day via nebulizer.
-Geriatric
40 mcg/day via nebulizer.
-Adolescents
Safety and efficacy of nebulization have not been established. Previously available inhalers were approved in children as young as 5 years of age.
-Children
Safety and efficacy of nebulization have not been established. Previously available inhalers were approved in children as young as 5 years of age.
-Infants
Safety and efficacy of nebulization have not been established.
Patients with Hepatic Impairment Dosing
Specific information regarding the need for formoterol dosage adjustment is not available; formoterol has not been studied in patients with hepatic impairment.
Patients with Renal Impairment Dosing
Formoterol has not been formally studied in patients with renal impairment; no dosage adjustment guidelines are available.
*non-FDA-approved indication
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 be used when formoterol 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 pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol 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 pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol 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 pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol 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 be used when formoterol 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 pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Acrivastine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects.
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.
Amphetamine: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine; dextroamphetamine and formoterol use. Concomitant use may potentiate sympathetic effects.
Amphetamine; Dextroamphetamine Salts: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine; dextroamphetamine and formoterol use. Concomitant use may potentiate sympathetic effects.
Amphetamine; Dextroamphetamine: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine; dextroamphetamine and formoterol use. Concomitant use may potentiate sympathetic effects.
Arformoterol: (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.
Articaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and formoterol 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.
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 be used when formoterol 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 be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Brompheniramine; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol 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 pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects.
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 formoterol 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.
Cetirizine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects.
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 be used when formoterol 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 pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Chlorpheniramine; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol 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 pseudoephedrine and formoterol 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.
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 pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Codeine; Phenylephrine; Promethazine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Desloratadine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Dextroamphetamine: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine; dextroamphetamine and formoterol use. Concomitant use may potentiate sympathetic effects.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol 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 pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Dichlorphenamide: (Moderate) Use dichlorphenamide and arformoterol or formoterol together with caution. Metabolic acidosis is listed by the manufacturers of arformoterol and formoterol as an adverse reaction seen with beta-2 agonists but would be rare with normal doses of arformoterol or formoterol. Metabolic acidosis has been reported with dichlorphenamide. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Diethylpropion: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Diphenhydramine; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Dobutamine: (Moderate) Caution and close observation should be used when formoterol 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 be used when formoterol 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.
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 be used when formoterol 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 be used when formoterol 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 formoterol 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 pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Fluticasone; Salmeterol: (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.
Fluticasone; Umeclidinium; Vilanterol: (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.
Fluticasone; Vilanterol: (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.
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.
Guaifenesin; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol 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 pseudoephedrine and formoterol 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.
Ibuprofen; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Indacaterol; Glycopyrrolate: (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.
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: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
Itraconazole: (Moderate) Use itraconazole with caution in combination with beta-agonists as concurrent use may increase the risk of QT prolongation. Itraconazole has been associated with prolongation of the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
Ketoconazole: (Moderate) Formoterol, as with other long-acting beta-agonists, should be administered with extreme caution to patients being treated with drugs known to prolong the QTc interval like ketoconazole because the effect of adrenergic agonists on the cardiovascular system may be potentiated. Drugs that are known to prolong the QTc interval have an increased risk of ventricular arrhythmias. Ketoconazole has been associated with prolongation of the QT interval and torsade de pointes (TdP).
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.
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: (Moderate) Formoterol, as with other long-acting beta-agonists, should be administered with extreme caution to patients being treated with drugs known to prolong the QTc interval like ketoconazole because the effect of adrenergic agonists on the cardiovascular system may be potentiated. Drugs that are known to prolong the QTc interval have an increased risk of ventricular arrhythmias. Ketoconazole has been associated with prolongation of the QT interval and torsade de pointes (TdP).
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 formoterol 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.
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.
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.
Loratadine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol 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 formoterol 36 hours before a methacholine challenge test. Beta-agonists inhibit the airway response to methacholine.
Methamphetamine: (Moderate) Caution and close observation should be used when formoterol 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 formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
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 pseudoephedrine and formoterol 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.
Norepinephrine: (Moderate) Caution and close observation should be used when formoterol 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.
Olodaterol: (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.
Phendimetrazine: (Moderate) Caution and close observation should be used when formoterol 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 phentermine and formoterol use. Concomitant use may potentiate sympathetic effects.
Phentermine; Topiramate: (Moderate) Monitor blood pressure and heart rate during concomitant phentermine and formoterol use. Concomitant use may potentiate sympathetic effects.
Phenylephrine: (Moderate) Caution and close observation should be used when formoterol 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.
Prilocaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and formoterol 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 be used when formoterol 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 pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Pseudoephedrine; Triprolidine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol 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: (Moderate) Due to a possible risk for QT prolongation, ribociclib and long-acting beta-agonists should be used together cautiously. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval like ribociclib. This risk may be more clinically significant with long-acting beta-agonists such as formoterol as compared to short-acting beta-agonists.
Ribociclib; Letrozole: (Moderate) Due to a possible risk for QT prolongation, ribociclib and long-acting beta-agonists should be used together cautiously. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval like ribociclib. This risk may be more clinically significant with long-acting beta-agonists such as formoterol as compared to short-acting beta-agonists.
Salmeterol: (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.
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.
Tiotropium; Olodaterol: (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.
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.
Umeclidinium; Vilanterol: (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.
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.
Inhaled formoterol acts locally in the lung as a bronchodilator. Similar to other beta-2 agonists, formoterol's mechanism of action involves stimulation of adenyl cyclase leading to the production of cyclic adenosine monophosphate (cAMP) via adenosine triphosphate (ATP). Increased levels of cAMP result in relaxation of the bronchial smooth muscle.
Formoterol, like salmeterol, is highly lipophilic. Formoterol enters the plasma cell membrane in the form of a depot and is gradually released into the aqueous phase to react with the beta-2 receptor, resulting in a long duration of action. The aqueous phase activity, not demonstrated by salmeterol, is responsible for the rapid onset of action of formoterol.
Formoterol has more than a 200-fold greater agonist activity at beta-2 receptors (primarily in the lung) than at beta-1 receptors (primarily in the heart). However, 10% to 50% of the beta receptors in the heart are beta-2 receptors and raise the possibility that even highly selective beta-2 receptor agonists may have adverse cardiovascular effects, such as tachycardia, palpitations and ischemia.
As with other beta-2 agonists, formoterol may possess antiinflammatory activity, but the clinical significance of this effect is unknown. In vitro studies have demonstrated inhibition of mast cell mediators such as histamine and leukotrienes. Monotherapy with formoterol is inappropriate due to lack of proven antiinflammatory and disease-modifying properties.
Formoterol is administered via nebulization. Formoterol is extensively metabolized in the liver by direct glucuronidation and O-demethylation followed by glucuronide conjugation. Four cytochrome P450 isoenzymes (CYP2D6, CYP2C19, CYP2C9, and CYP2A6) are involved in the O-demethylation of formoterol. Formoterol has not been shown to inhibit CYP450 isoenzymes. About 60% of a dose is eliminated in the urine and 33% in the feces over a period of 104 hours. In the urine, roughly 10% of a dose is excreted unchanged and roughly 15% is eliminated as the direct glucuronide conjugate. The mean terminal elimination half-life is roughly 10 hours.
-Route-Specific Pharmacokinetics
Inhalation Route
-Dry powder inhalers: Following inhalation of a single 120 mcg dose (10 times the recommended dose) by healthy subjects, a minimal amount of formoterol was absorbed into plasma within 5 minutes of dosing. Some accumulation in plasma occurs with multiple doses. Most of the inhaled formoterol delivered to the bloodstream is swallowed and absorbed from the GI tract. Bronchodilation begins to occur in 1 to 3 minutes. The onset of therapeutic effects, as measured by a 15% improvement in forced expiratory flow in one second (FEV-1), occurs in approximately 15 minutes. In clinical trials, most patients experienced the maximum improvement in FEV-1 after inhalation of a 12 mcg dose within 1 to 3 hours. Significant increases in lung function and reduction in asthmatic symptoms are evident by the second week of treatment.
-Special Populations
Hepatic Impairment
Formoterol pharmacokinetics have not been studied in those with hepatic impairment.
Renal Impairment
Formoterol pharmacokinetics have not been studied in those with renal impairment.
Pediatrics
Limited data are available in pediatric patients. In a study of children 5 years and older with asthma, formoterol accumulation did not exceed that seen in adults. Approximately 6% and 6.5% to 9% of the dose was recovered in the urine of the children as unchanged and conjugated formoterol, respectively.
Geriatric
Formoterol pharmacokinetics have not been studied in the elderly.
Gender Differences
No gender differences have been noted for formoterol.