Brand name: Bevespi Aerosphere (combination)
Drug class: Selective beta-2-Adrenergic Agonists
VA class: RE102
Chemical name: (±)-2′-Hydroxy-5′-[(R*)-1-hydroxy-2-[[(R*)-p-methoxy-α-methylphenethyl]amino]ethyl]formanilide fumarate
Molecular formula: C₁₉H₂₄N₂O₄)₂•C₄H₄O₄
CAS number: 43229-80-7

Medically reviewed by Drugs.com on Nov 22, 2023. Written by ASHP.

Introduction

Bronchodilator; a relatively selective, long-acting β₂-adrenergic agonist.

Uses for Formoterol

Bronchospasm in Asthma

Formoterol: Used concomitantly with long-term asthma controller therapy (e.g., inhaled corticosteroids) for prevention of bronchospasm in patients with reversible obstructive airway disease (e.g., asthma).

Monotherapy with long-acting β₂-adrenergic agonists (e.g., formoterol) increases the risk of asthma-related death and may increase the risk of asthma-related hospitalization in children and adolescents. Use of formoterol alone for treatment of asthma without concomitant use of long-term asthma controller therapy (e.g., inhaled corticosteroids) is contraindicated. (See Asthma-related Death and Serious Asthma-related Events under Cautions.)

Formoterol in fixed combination with budesonide or mometasone (formoterol/budesonide, formoterol/mometasone): Treatment of asthma only in patients not responding adequately to long-term asthma controller therapy (e.g., inhaled corticosteroids) or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a long-acting β₂-adrenergic agonist.

Once asthma control achieved and maintained, assess patient at regular intervals and step down therapy (e.g., discontinue formoterol or formoterol/budesonide) if possible without loss of asthma control, and maintain patient on long-term asthma controller therapy (e.g., inhaled corticosteroids).

Do not use formoterol/budesonide in patients with asthma adequately controlled on low or medium dosage of inhaled corticosteroids.

Formoterol alone or in fixed combination with budesonide or mometasone not indicated for relief of acute bronchospasm; donotinitiate in patients with rapidly deteriorating or potentially life-threatening episodes of asthma. (See Acute Exacerbations of Asthma or COPD under Cautions.)

Bronchospasm in COPD

Formoterol, formoterol/budesonide, or formoterol in fixed combination with glycopyrrolate (formoterol/glycopyrrolate): Long-term maintenance treatment of bronchospasm or airflow obstruction associated with COPD, including chronic bronchitis and emphysema.

Do not initiate formoterol alone or in fixed combination with budesonide or glycopyrrolate in patients with substantially worsening or acutely deteriorating COPD; donotuse to treat acute symptoms. (See Acute Exacerbations of Asthma or COPD under Cautions.)

Use of long-acting β₂ agonists (e.g., formoterol) with or without inhaled corticosteroids for acute exacerbations of COPD not evaluated. Use a short-acting inhaled β₂-adrenergic agonist intermittently (as needed) for acute symptoms of COPD.

Related/similar drugs

Breztri Aerosphere, prednisone, albuterol, montelukast, azithromycin, Symbicort, Singulair

Formoterol Dosage and Administration

General

• When initiating formoterol alone or in fixed combination with budesonide, glycopyrrolate, or mometasone, discontinue regular use of short-acting, oral or inhaled β₂-adrenergic agonists; use such agents only for relief of acute symptoms of asthma or COPD not controlled by formoterol.

• If a formoterol dose alone or in fixed combination with budesonide, glycopyrrolate, or mometasone is missed, skip that dose and take the next dose at the usual time. Do not double the dose to replace the missed dose.

• Failure to respond to a previously effective dosage may indicate seriously worsening asthma or destabilization of COPD that requires reevaluation. Extra or increased doses of formoterol are not recommended. (See Acute Exacerbations of Asthma or COPD under Cautions.)

• Administer a short-acting, inhaled β₂-agonist to relieve acute asthmatic or COPD symptoms.

Administration

Oral Inhalation

Formoterol: Administer by oral inhalation as an oral inhalation solution (Perforomist) via nebulization.

Fixed combinations of formoterol/budesonide (Symbicort), formoterol/glycopyrrolate (Bevespi Aerosphere), and formoterol/mometasone (Dulera): Administer by oral inhalation using a metered-dose aerosol inhaler with hydrofluoroalkane (HFA) propellant.

Inhalation Solution

Administer twice daily, approximately every 12 hours (morning and evening).

Store single-dose vials of oral inhalation solution in the foil pouch provided; remove immediately before use.

For administration of inhalation solution via nebulization, open a 20-mcg vial and squeeze entire contents into nebulizer reservoir. Connect reservoir to mouthpiece or face mask and then to compressor according to manufacturer’s instructions.

Instruct patient to sit in an upright, comfortable position and then to breathe as calmly, deeply, and evenly as possible through the mouth using the mouthpiece or face mask of the nebulizer until device stops producing mist, about 9 minutes.

Clean nebulizer after use according to manufacturer’s instructions.

Safety and efficacy of formoterol inhalation solution delivered from a nebulizer other than the Pari-LC Plus nebulizer or a compressor other than the PRONEB Ultra compressor not established.

Do not mix with other inhalation solutions. Do not ingest the oral inhalation solution.

Inhalation Aerosol

Administer aerosol containing formoterol/budesonide, formoterol/glycopyrrolate, or formoterol/mometasone as 2 inhalations twice daily (morning and evening). After inhalation of formoterol/budesonide or formoterol/mometasone, rinse mouth and spit out water.

Use actuator supplied with the product to administer formoterol in fixed combination with budesonide, glycopyrrolate, or mometasone.

Formoterol/budesonide: Test spray 2 times into the air (away from face) before first use, if not used for >7 days, or if dropped; shake well for 5 seconds before each spray. Shake well for 5 seconds immediately prior to use. Clean inhaler every 7 days by wiping mouthpiece with a dry cloth.

Formoterol/glycopyrrolate: Shake well before each inhalation. Prime the inhaler before first use. Test spray 4 times into the air (away from face) before initial use; if not used for >7 days, repeat priming process (using only 2 sprays instead of 4). Clean inhaler once weekly by removing the canister from the actuator; do not clean the canister or allow it to get wet. Rinse the actuator under warm water for about 30 seconds then turn upside down and rinse again. Allow actuator to dry overnight. Repeat priming of the inhaler after cleaning by shaking well and releasing 2 test sprays into the air.

Formoterol/mometasone: Test spray 4 times into the air (away from face) before initial use or if not used for >5 days; shake well before each test spray and each inhalation. Clean inhaler every 7 days by wiping mouthpiece with a dry cloth; do not wash inhaler in water.

Dosage

Each 2-mL single-dose vial of formoterol fumarate oral inhalation solution (Perforomist) contains 20 mcg of formoterol fumarate. Dilution not required prior to administration by nebulization. Amount of drug delivered to the lungs will depend on patient factors and type of nebulization system used and its performance.

Each actuation of the oral aerosol inhaler containing formoterol/budesonide (Symbicort) delivers 5.1 mcg of formoterol fumarate dihydrate and 91 or 181 mcg of budesonide from the valve and delivers 4.5 mcg of formoterol fumarate dihydrate and 80 or 160 mcg of budesonide from the actuator per metered spray, depending on preparation used. Strength of the preparation and dosage of the drug are expressed in terms of drug delivered from mouthpiece of the actuator. Actual amount of drug delivered to the lungs depends on factors such as patient’s coordination between actuation of the inhaler and inspiration through the delivery system. Symbicort aerosol inhaler delivers 60 metered sprays per 6- or 6.9-g canister and 120 metered sprays per 10.2-g canister.

After priming, each actuation of the oral aerosol inhaler containing formoterol/glycopyrrolate (Bevespi Aerosphere) delivers 5.5 mcg of formoterol fumarate and 10.4 mcg of glycopyrrolate (equivalent to 8.3 mcg of glycopyrronium) from the valve and delivers 4.8 mcg of formoterol fumarate and 9 mcg of glycopyrrolate (equivalent to 7.2 mcg of glycopyrronium) from the actuator. Actual amount of drug delivered to the lungs depends on factors such as patient's coordination between actuation of the device and inspiration through the delivery system. Bevespi Aerosphere inhalation aerosol delivers 28 or 120 metered sprays per 5.9- or 10.7-g canister, respectively.

Each actuation of the oral aerosol inhaler containing formoterol/mometasone (Dulera) delivers 5.5 mcg of formoterol fumarate dihydrate and 115 or 225 mcg of mometasone furoate from the valve and delivers 5 mcg of formoterol fumarate dihydrate and 100 or 200 mcg of mometasone furoate from the actuator per metered spray, depending on preparation used. Strength of the preparation and dosage of the drug are expressed in terms of drug delivered from mouthpiece of the actuator. Actual amount of drug delivered to the lungs may depend on factors such as patient's coordination between actuation of the device and inspiration through the delivery system. Dulera aerosol inhaler delivers 60 or 120 metered sprays per 8.8- or 13-g canister, respectively.

Pediatric Patients

Asthma

Formoterol/Budesonide Fixed Combination

Oral Inhalation (Aerosol)

Children 6 to <12 years of age: 9 mcg of formoterol fumarate dihydrate and 160 mcg of budesonide (2 inhalations of preparation containing 4.5 mcg of formoterol fumarate dihydrate/80 mcg of budesonide) twice daily.

Adolescents ≥12 years of age: 9 mcg of formoterol fumarate dihydrate and 160 or 320 mcg of budesonide (2 inhalations of preparation containing 4.5 mcg of formoterol fumarate dihydrate/80 or 160 mcg of budesonide) twice daily. Base initial dosage on asthma severity.

If control of asthma in adolescents ≥12 years of age inadequate after 1–2 weeks of therapy at lower dosage, switching to higher strength of the fixed combination (higher strengths contain higher dosages of budesonide only) may provide additional asthma control.

Formoterol/Mometasone Fixed Combination

Oral Inhalation (Aerosol)

Adolescents ≥12 years of age: 10 mcg of formoterol fumarate dihydrate and 200 or 400 mcg of mometasone furoate (2 inhalations of preparation containing 5 mcg of formoterol fumarate dihydrate/100 or 200 mcg of mometasone furoate) twice daily. Select initial dosage based on asthma severity, previous asthma therapy (including previous inhaled corticosteroid dosage), current control of asthma symptoms, and risk of future asthma exacerbations.

If control of asthma inadequate after 2 weeks of therapy at lower dosage, switching to higher strength preparation of the fixed combination (higher strengths contain higher dosages of mometasone only) may provide additional asthma control.

Adults

Asthma

Formoterol/Budesonide Fixed Combination

Oral Inhalation (Aerosol)

9 mcg of formoterol fumarate dihydrate and 160 or 320 mcg of budesonide (2 inhalations of preparation containing 4.5 mcg of formoterol fumarate dihydrate/80 or 160 mcg of budesonide) twice daily. Base initial dosage on asthma severity.

If control of asthma inadequate after 1–2 weeks of therapy at lower dosage, switching to higher strength of the fixed combination (higher strengths contain higher dosages of budesonide only) may provide additional asthma control.

Formoterol/Mometasone Fixed Combination

Oral Inhalation (Aerosol)

10 mcg of formoterol fumarate dihydrate and 200 or 400 mcg of mometasone furoate (2 inhalations of preparation containing 5 mcg of formoterol fumarate dihydrate/100 or 200 mcg of mometasone furoate) twice daily. Select initial dosage based on asthma severity, previous asthma therapy (including previous inhaled corticosteroid dosage), current control of asthma symptoms, and risk of future asthma exacerbations.

If control of asthma inadequate after 2 weeks of therapy at lower dosage, switching to higher strength of the fixed combination (higher strengths contain higher dosages of mometasone only) may provide additional asthma control.

COPD

Formoterol

Oral Inhalation (Solution)

20 mcg (entire contents of single-dose vial) every 12 hours via nebulization.

Formoterol/Budesonide Fixed Combination

Oral Inhalation (Aerosol)

9 mcg of formoterol fumarate dihydrate and 320 mcg of budesonide (2 inhalations of preparation containing 4.5 mcg of formoterol fumarate dihydrate/160 mcg of budesonide) twice daily.

Lower dosages (i.e., 9 mcg of formoterol fumarate dihydrate and 160 mcg of budesonide twice daily) not recommended; no additional improvement in lung function (e.g., FEV₁) compared with formoterol alone or placebo.

Formoterol/Glycopyrrolate Fixed Combination

Oral Inhalation (Aerosol)

9.6 mcg of formoterol fumarate and 18 mcg of glycopyrrolate (2 inhalations of preparation containing 4.8 mcg of formoterol fumarate/9 mcg of glycopyrrolate) twice daily.

Prescribing Limits

Pediatric Patients

Asthma

Formoterol/Budesonide Fixed Combination

Oral Inhalation (Aerosol)

Children 6 to <12 years of age: Maximum 9 mcg of formoterol fumarate dihydrate and 160 mcg of budesonide twice daily.

Adolescents ≥12 years of age: Maximum 9 mcg of formoterol fumarate dihydrate and 320 mcg of budesonide twice daily.

Formoterol/Mometasone Fixed Combination

Oral Inhalation (Aerosol)

Adolescents ≥12 years of age: Maximum 10 mcg of formoterol fumarate dihydrate and 400 mcg of mometasone twice daily.

Adults

Asthma

Formoterol/Budesonide Fixed Combination

Oral Inhalation (Aerosol)

Maximum 9 mcg of formoterol fumarate dihydrate and 320 mcg of budesonide twice daily.

Formoterol/Mometasone Fixed Combination

Oral Inhalation (Aerosol)

Maximum 10 mcg of formoterol fumarate dihydrate and 400 mcg of mometasone furoate twice daily.

COPD

Formoterol

Oral Inhalation (Solution)

Maximum 40 mcg daily.

Formoterol/Budesonide Fixed Combination

Oral Inhalation (Aerosol)

Maximum 9 mcg of formoterol fumarate dihydrate and 320 mcg of budesonide twice daily.

Formoterol/Glycopyrrolate Fixed Combination

Oral Inhalation (Aerosol)

Maximum 9.6 mcg of formoterol fumarate and 18 mcg of glycopyrrolate twice daily.

Special Populations

Hepatic Impairment

Formoterol: No specific dosage recommendations at this time.

Formoterol in fixed combination with budesonide, glycopyrrolate, or mometasone: Closely monitor patients with hepatic impairment. (See Special Populations under Pharmacokinetics.)

Renal Impairment

Formoterol alone or in fixed combination with budesonide or mometasone: No specific dosage recommendations.

Formoterol in fixed combination with glycopyrrolate: Use in patients with severe renal impairment (Cl_cr ≤30 mL/minute) or those with end-stage renal disease requiring dialysis only if expected benefit outweighs potential risk.

Geriatric Patients

Formoterol: No specific dosage recommendations at this time.

Formoterol in fixed combination with budesonide, glycopyrrolate, or mometasone: No dosage adjustment required.

Cautions for Formoterol

Contraindications

• Formoterol: Contraindicated for treatment of asthma without concomitant use of long-term asthma controller therapy (e.g., inhaled corticosteroids) because of risk of asthma-related death and hospitalization. (See Asthma-related Death and Serious Asthma-related Events under Cautions.)

• Formoterol/budesonide and formoterol/mometasone: Contraindicated as primary treatment of status asthmaticus or other acute episodes of asthma or COPD when intensive measures required.

• Formoterol/glycopyrrolate: Not indicated for treatment of asthma.

• Formoterol alone or in fixed combination with budesonide, glycopyrrolate, or mometasone: Known hypersensitivity to formoterol or any ingredient in the formulation.

Warnings/Precautions

Warnings

Use of Fixed Combinations

When formoterol used in fixed combination with budesonide, glycopyrrolate, or mometasone, consider cautions, precautions, contraindications, and interactions associated with budesonide, glycopyrrolate, or mometasone.

Asthma-related Death and Serious Asthma-related Events

Increased risk of asthma-related death reported with long-acting β₂-adrenergic agonists (e.g., formoterol) when used as monotherapy. Data from clinical trials also suggest that use of long-acting β₂-adrenergic agonists as monotherapy increases the risk of asthma-related hospitalization in children and adolescents.

Use of long-acting β₂-adrenergic agonists, including formoterol, alone for treatment of asthma without concomitant use of long-term asthma controller therapy (e.g., inhaled corticosteroids) is contraindicated because of increased risk of asthma-related death and hospitalization.

Use long-acting β₂-adrenergic agonists, including formoterol, only as additional therapy in patients with asthma currently receiving long-term asthma controller therapy (e.g., inhaled corticosteroids) but whose disease is inadequately controlled with such therapy.

Use formoterol/budesonide and formoterol/mometasone only in patients with asthma not responding adequately to long-term asthma controller therapy, (e.g., inhaled corticosteroids) or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a long-acting β₂-adrenergic agonist. (See Bronchospasm in Asthma under Uses.)

Large safety study (Salmeterol Multicenter Asthma Research Trial [SMART]) showed an increase in asthma-related deaths in patients receiving salmeterol. While no adequate studies conducted to determine whether the rate of asthma-related death is increased with formoterol, data suggest a higher incidence of serious asthma exacerbations with formoterol compared with placebo. Increased risk of asthma-related death with use of salmeterol as monotherapy is considered a class effect of the long-acting β₂-adrenergic agonists, including formoterol.

Based on review of 4 clinical trials (3 in adults and adolescents and 1 in children), FDA concluded there is no clinically important increased risk of serious asthma-related events (i.e., asthma-related hospitalization, intubation, death) associated with use of fixed-combination therapy with long-acting β₂-adrenergic agonists and inhaled corticosteroids compared with use of inhaled corticosteroids alone for the treatment of asthma. These studies also showed that fixed-combination therapy with long-acting β₂-adrenergic agonists and inhaled corticosteroids reduced the incidence of asthma exacerbations compared with use of inhaled corticosteroids alone.

No adequate studies conducted to determine whether the rate of death is increased in patients with COPD receiving long-acting β₂-adrenergic agonists.

Acute Exacerbations of Asthma or COPD

Do not initiate formoterol in patients with acutely deteriorating or substantially worsening asthma, which may be life-threatening; fatalities reported with orally inhaled sympathomimetic drugs. Do not initiate formoterol in fixed combination with budesonide, glycopyrrolate, or mometasone in patients with rapidly deteriorating or potentially life-threatening episodes of asthma or COPD.

Failure to respond to a previously effective dosage may indicate substantially worsening asthma or destabilization of COPD that requires prompt reevaluation. Promptly reevaluate asthma therapy if inadequate control of symptoms persists despite supplemental short-acting β₂-agonist bronchodilator therapy (i.e., need to increase dose or frequency of administration). Reevaluation of asthma therapy may require dosage adjustment of inhaled corticosteroid or initiation of systemic corticosteroids. Do not use extra or increased doses of formoterol in such situations.

If asthma deteriorates in patients receiving formoterol in fixed combination with budesonide or mometasone, prompt reevaluation of asthma therapy is required with special consideration given to the possible need for increasing the strength of the fixed combination (higher strengths contain higher dosages of budesonide or mometasone only), adding additional inhaled corticosteroids, or initiating systemic corticosteroids; do not increase the frequency of administration of formoterol/budesonide or formoterol/mometasone.

Do not use formoterol/budesonide or formoterol/mometasone to relieve symptoms of acute asthma and do not use formoterol/glycopyrrolate to treat acutely deteriorating COPD. Use a short-acting, inhaled β₂-adrenergic agonist intermittently (as needed) for acute symptoms of asthma or COPD.

When initiating formoterol alone or in fixed combination with budesonide, glycopyrrolate, or mometasone, discontinue regular use (e.g., 4 times daily) of short-acting, inhaled β₂-agonists and use only for relief of acute asthma or COPD symptoms.

Serious exacerbations, including fatalities, reported in patients receiving formoterol.

Excessive Doses

Possible fatalities and/or serious cardiovascular effects reported in association with excessive use of inhaled sympathomimetic drugs.

Do not use additional formoterol or other long-acting inhaled β₂-adrenergic agonists for any reason in patients receiving formoterol alone or in fixed combination with budesonide, glycopyrrolate, or mometasone.

Concomitant Anti-inflammatory Therapy

No data available demonstrating clinical anti-inflammatory effects of formoterol expected to substitute for or allow reduction in dosage of corticosteroids.

Particular care is needed for patients transferring from systemic to orally inhaled corticosteroids since death resulting from adrenal insufficiency occurred in some asthmatic patients during and after such transfer.

Cardiovascular Effects

Possible clinically important changes in SBP and/or DBP, heart rate, and ECG (e.g., flattening of T wave, prolongation of QT_c interval, ST-segment depression) changes. May require discontinuance of the drug. Use with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Nervous System Effects

Use with caution in patients with seizure disorders.

Paradoxical Bronchospasm

Possible acute, life-threatening bronchospasm may occur immediately upon inhalation of formoterol. Discontinue therapy immediately and institute alternative therapy.

Sensitivity Reactions

Immediate hypersensitivity reactions (e.g., anaphylaxis, urticaria, angioedema, rash, flushing, allergic dermatitis, bronchospasm) reported. Discontinue formoterol/glycopyrrolate immediately if such allergic reactions occur, particularly angioedema (e.g., difficulties with breathing or swallowing; swelling of the tongue, lips, or face), urticaria, or rash; consider alternative therapy.

General Precautions

Metabolic Effects

Possible clinically important changes in blood glucose; possible clinically important decreases in serum potassium. Hypokalemia is usually transient, not requiring supplementation.

Use with caution in patients with thyrotoxicosis and in those unusually responsive to sympathomimetic amines.

Specific Populations

Pregnancy

Category C.

No adequate and well-controlled studies in pregnant women.

May interfere with uterine contractility. Carefully weigh benefit versus risk in labor.

Lactation

Distributed into milk in rats. Not known whether formoterol is distributed into human milk. Data also not available on the drug’s effects on the breast-fed child or milk production.

When using formoterol alone or in fixed combination with budesonide or mometasone, consider benefits of breast-feeding and importance of the drug to the woman; also consider any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

When using formoterol in fixed combination with glycopyrrolate, discontinue nursing or the drug.

Pediatric Use

Formoterol alone or in fixed combination with glycopyrrolate: Not indicated for use in children. Safety and efficacy not established in children.

Formoterol in fixed combination with budesonide: Safety and efficacy in children ≥12 years of age with asthma established in studies of up to 12 months’ duration. Safety and efficacy in children 6 to <12 years of age with asthma established in studies of up to 12 weeks’ duration. Safety and efficacy in children <6 years of age not established. (See Bronchospasm in Asthma under Uses.)

Formoterol in fixed combination with mometasone: Safety and efficacy in children ≥12 years of age with asthma established in studies of up to 12 months' duration. Safety and efficacy in children <12 years of age not established.

Available data suggest that monotherapy with long-acting β₂-adrenergic agonists may increase the risk of asthma-related death and hospitalization in children and adolescents. (See Asthma-related Death and Serious Asthma-related Events under Cautions.)

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults. Possibility that some geriatric patients may exhibit increased sensitivity cannot be ruled out. (See Geriatric Patients under Dosage and Administration.)

Common Adverse Effects

Formoterol in patients with COPD: Diarrhea, nausea, vomiting, nasopharyngitis, dry mouth, dizziness, insomnia.

Formoterol/budesonide in patients with asthma: Nasopharyngitis, headache, upper respiratory tract infection, pharyngolaryngeal pain, sinusitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, oral candidiasis.

Formoterol/budesonide in patients with COPD: Nasopharyngitis, oral candidiasis, bronchitis, sinusitis, upper respiratory tract infection.

Formoterol/glycopyrrolate in patients with COPD: Urinary tract infection, cough.

Formoterol/mometasone in patients with asthma: Nasopharyngitis, sinusitis, headache.

Drug Interactions

The following information addresses potential interactions with formoterol. When formoterol is used in fixed combination with budesonide, glycopyrrolate, or mometasone, consider interactions associated with budesonide, glycopyrrolate, or mometasone. No formal drug interaction studies performed to date with the fixed-combination preparations.

Formoterol metabolized in the liver by CYP isoenzymes 2D6, 2C19, 2C9, and 2A6.

Drugs that Prolong QT Interval

Potential pharmacologic interaction (increased risk of ventricular arrhythmias and possible potentiation of formoterol effects on cardiovascular system). Use extreme caution during concomitant therapy.

Specific Drugs

Formoterol Pharmacokinetics

Absorption

Bioavailability

Formoterol rapidly absorbed following inhalation; peak plasma concentrations usually attained within 5–10 minutes.

Onset

Maximum improvement in forced expiratory volume in 1 second (FEV₁): 2–3 hours.

Duration

12 hours.

Distribution

Extent

Distributed into milk in animals. Not known if distributed into milk in humans.

Plasma Protein Binding

46–64% bound to plasma proteins; binding to serum albumin is 31–38%.

Elimination

Metabolism

Metabolized in the liver by CYP isoenzymes 2D6, 2C19, 2C9, and 2A6.

Elimination Route

Eliminated in feces (24–34%) and in urine (59–62%).

Half-life

7 hours.

Special Populations

Possible increased exposure in patients with severe hepatic impairment.

Stability

Storage

Oral Inhalation

Solution

Formoterol: Prior to dispensing, 2–8°C; protect from light and heat.

After dispensing, 2–8°C until drug expires or at 20–25°C up to 3 months; protect from light and heat.

Do not remove single-use vials from their foil pouch until immediately before use.

Aerosol

Formoterol/budesonide: 20–25°C with mouthpiece down. Contents under pressure; do not puncture, use or store near heat or an open flame, or place into a fire or incinerator. Exposure to temperatures >49°C may cause canister to burst. Discard inhaler when labeled number of inhalations used or within 3 months after removal from foil package. Never immerse canister in water to determine amount of drug remaining (“float test”).

Formoterol/glycopyrrolate: 20–25°C (may be exposed to 15–30°C). Discard 3 months after foil pouch opened or when dose indicator reads “0”, whichever comes first. Contents under pressure; do not puncture, use or store near heat or an open flame, or place into a fire or incinerator. Exposure to temperatures >49°C may cause canister to burst. Never immerse canister in water to determine amount of drug remaining (“float test”).

Formoterol/mometasone: 20–25°C with mouthpiece down (may be exposed to 15–30°C). Protect from excessive heat. Do not puncture, use or store near heat or open flame, or place into a fire or incinerator. Discard when dose counter reads “0”.

Actions

• Formoterol is a synthetic sympathomimetic amine.

• Long-acting, selective β₂-receptor agonist.

• Stimulates β₂-adrenergic receptors with little or no effect on β₁- or α-adrenergic receptors.

• Activates adenyl cyclase and stimulates production of cyclic adenosine-3′,5′-monophosphate (cAMP). Increased concentrations of cAMP relax bronchial smooth muscle and inhibit release of proinflammatory mast-cell mediators (e.g., histamine, leukotrienes).

• Inhibits allergen-induced infiltration of eosinophils into airways and reduces extravasation of plasma proteins (e.g., albumin). Does not possess clinically important anti-inflammatory effects.

• Prolonged therapy at greater than recommended dosages may be associated with development of tolerance to the bronchodilatory effects.

Advice to Patients

• When used in fixed combination with budesonide, glycopyrrolate, or mometasone, importance of informing patients of important cautionary information about budesonide, glycopyrrolate, or mometasone.

• A copy of the manufacturer’s patient information (medication guide) for formoterol alone or in fixed combination with budesonide, glycopyrrolate, or mometasone must be provided to all patients with each prescription of the drug. Importance of instructing patients to read the medication guide prior to initiation of therapy and each time prescription is refilled.

• Importance of informing patients that monotherapy with long-acting β₂-adrenergic agonists, including formoterol, increases risk of asthma-related death and may increase risk of asthma-related hospitalization in children and adolescents.

• Importance of informing patients that long-term asthma controller drugs must be continued when formoterol is added to the treatment regimen.

• Importance of children receiving therapy under adult supervision.

• Importance of adequate understanding of proper storage, preparation, and use of oral inhalation delivery systems.

• Importance of correct procedure for administering formoterol-containing therapy and concomitant therapy (e.g., a short-acting β₂-adrenergic agonist). Importance of not breathing into inhaler.

• Importance of adherence to dosing schedules of formoterol alone or in fixed combination with budesonide, glycopyrrolate, or mometasone and any concomitant therapy, including not altering the dose or frequency of use of such drugs unless otherwise instructed by a clinician.

• Importance of advising patients that if a dose of formoterol alone or in fixed combination with budesonide, glycopyrrolate, or mometasone is missed, the next dose should be taken at the regularly scheduled time; the dose should not be doubled.

• Importance of informing patients of adverse effects associated with long-acting β₂-adrenergic agonists such as palpitations, chest pain, rapid heart rate, tremor, or nervousness.

• Importance of understanding that formoterol-containing therapy does not relieve acute symptoms of asthma or COPD. Importance of all patients being provided with and instructed in the use of a short-acting, inhaled β₂-adrenergic bronchodilator as supplemental therapy for acute asthma or COPD symptoms.

• Importance of discontinuing regular use of a short-acting, inhaled β-adrenergic bronchodilator when initiating therapy with formoterol and instituting intermittent use of a short-acting bronchodilator (not formoterol) to relieve acute symptoms of asthma.

• Importance of contacting a clinician if respiratory symptoms worsen or are not relieved by usual dosage of formoterol fumarate. Importance of contacting a clinician or obtaining emergency medical care if 4 or more inhalations of a short-acting β₂-agonist are required daily for 2 or more consecutive days, an entire canister of the short-acting β₂-agonist is used in 8 weeks, peak flow meter results decrease, or asthma symptoms do not improve after 1 week of formoterol therapy.

• Importance of instructing patients to seek emergency medical care if breathing problems worsen rapidly and usual doses of a short-acting bronchodilator do not relieve acute asthma or COPD symptoms.

• Importance of advising patients receiving formoterol-containing preparations not to use additional formoterol or other long-acting inhaled β₂-adrenergic agonists for any reason.

• Importance of patients not discontinuing formoterol-containing therapy and not discontinuing or reducing concomitant asthma therapy without medical supervision, since symptoms may worsen.

• Importance of promptly contacting clinicians or seeking emergency medical care if symptoms of a serious allergic reaction (e.g., rash, hives, breathing problems, swelling of the face, tongue, or mouth) develop.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as concomitant illnesses (e.g., heart disease, hypertension, seizures, thyroid problems, diabetes mellitus, drug or food allergies).

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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