Formoterol Fumarate

Pronunciation

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
Brands: Foradil, Symbicort

Warning(s)

  • Long-acting β2-adrenergic agonists (e.g., formoterol) increase the risk of asthma-related death and may increase the risk of asthma-related hospitalization in children and adolescents.1 41 48 (See Asthma-related Death under Cautions.)

  • Data currently inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma controller therapy mitigates the increased risk of asthma-related death from long-acting β2-adrenergic agonists.1 48

  • Use of formoterol for treatment of asthma without concomitant use of long-term asthma controller therapy (e.g., inhaled corticosteroids) is contraindicated.1 41 (See Contraindications under Cautions.)

  • Use 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.1 41 (See Bronchospasm in Asthma under Uses.)

  • Use formoterol in fixed combination with budesonide 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.48

REMS:

FDA approved a REMS for formoterol to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of formoterol and consists of the following: communication plan. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Bronchodilator; a relatively selective, long-acting β2-adrenergic agonist.1

Uses for Formoterol Fumarate

Bronchospasm in Asthma

Formoterol is used only 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).1 7 15 16 18 19

Long-acting β2-adrenergic agonists (e.g., formoterol) increase the risk of asthma-related death and may increase the risk of asthma-related hospitalization in children and adolescents.1 41 48 Use of formoterol for treatment of asthma without concomitant use of long-term asthma controller therapy (e.g., inhaled corticosteroids) is contraindicated.1 41 (See Boxed Warning and also Asthma-related Death under Cautions.)

Formoterol is used 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.1

Formoterol in fixed combination with budesonide is used 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.48

Slideshow: Flashback: FDA Drug Approvals 2013

Once asthma control achieved and maintained, assess patient at regular intervals and step down therapy (e.g., discontinue formoterol or formoterol in fixed combination with budesonide) if possible without loss of asthma control, and maintain patient on long-term asthma controller therapy (e.g., inhaled corticosteroids).1 41 48

Formoterol is not a substitute for corticosteroids; corticosteroid therapy should not be stopped or reduced in dosage when formoterol is initiated.1 (See Concomitant Anti-inflammatory Therapy under Cautions.)

Do not use formoterol or formoterol in fixed combination with budesonide in patients with asthma adequately controlled on low or medium dosage of inhaled corticosteroids.1 48

In children and adolescents with asthma requiring addition of a long-acting β2-adrenergic agonist to an inhaled corticosteroid, generally use a fixed-combination preparation containing both an inhaled corticosteroid and a long-acting β2-adrenergic agonist to ensure compliance with both drugs.1

When separate administration of long-term asthma controller therapy (e.g., inhaled corticosteroids) and a long-acting β2-adrenergic agonist is clinically indicated, take appropriate steps to ensure compliance with both drugs.1 If compliance cannot be ensured, a fixed-combination preparation containing both an inhaled corticosteroid and a long-acting β2-adrenergic agonist is recommended.1

Do not initiate formoterol in patients with substantially worsening or acutely deteriorating asthma; do not use to treat acute symptoms of asthma.1 Formoterol in fixed combination with budesonide not indicated for relief of acute bronchospasm; do not initiate in patients with rapidly deteriorating or potentially life-threatening episodes of asthma.48 (See Acute Exacerbations of Asthma or COPD under Cautions.)

Exercise-induced Bronchospasm

Formoterol is used for prevention of exercise-induced bronchospasm when administered on an occasional, as-needed basis.1 17

Use of formoterol as a single agent for prevention of exercise-induced bronchospasm may be clinically indicated in patients without persistent asthma.1

Use of formoterol for prevention of exercise-induced bronchospasm may be clinically indicated in patients with persistent asthma; however, treatment of asthma should include long-term asthma controller therapy (e.g., inhaled corticosteroids).1

Bronchospasm in COPD

Formoterol alone or in fixed combination with budesonide is used for long-term treatment of bronchospasm associated with COPD, including chronic bronchitis and emphysema.1 19 23 24 48

Use of long-acting β2 agonists with or without inhaled corticosteroids for acute exacerbations of COPD not evaluated.35 Use a short-acting inhaled β2-adrenergic agonist intermittently (as needed) for acute symptoms of COPD.33 34 35

Formoterol Fumarate Dosage and Administration

General

  • When initiating formoterol alone or in fixed combination with budesonide, 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.1 48

  • If a formoterol dose alone or in fixed combination with budesonide is missed, skip that dose and take the next dose at the usual time.11 44 48 Do not double the dose to replace the missed dose.11 44 48

  • Failure to respond to a previously effective dosage may indicate seriously worsening asthma or destabilization of COPD that requires reevaluation.1 18 48 Extra or increased doses of formoterol are not recommended.1 6 10 11 48 (See Acute Exacerbations of Asthma under Cautions.)

  • Administer a short-acting, inhaled β2-agonist to relieve acute asthmatic symptoms.1 48 Administer a short-acting β2-adrenergic agonist if routine therapy with formoterol is not effective for preventing exercise-induced bronchospasm.1

Administration

Oral Inhalation

Administer oral inhalation powder using a special oral inhaler (Foradil Aerolizer) that delivers powdered drug from capsules.1 11 44 Do not take capsules orally.1 11 44 45 (See Accidental Oral Ingestion under Cautions.)

Administer oral inhalation aerosol (Symbicort) using an aerosol inhaler device with hydrofluoroalkane (HFA) propellant.48

Inhalation Powder

Administer twice daily, approximately every 12 hours (morning and evening).1 11 44

For prevention of exercise-induced bronchospasm, administer ≥15 minutes before exercise, but not more often than once every 12 hours.1 11 44

Do not use formoterol dry-powder capsules with any capsule inhaler other than Aerolizer.1 11 44 Do not swallow the dry-powder capsule.44 45 If no improvement, ensure patient is using the inhaler rather than swallowing the dry-powder capsules.45 (See Accidental Oral Ingestion under Cautions.)

Do not use spacer devices with the Aerolizer inhaler.44

Inhalation Aerosol

Administer twice daily (morning and evening).48

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.48

Shake well for 5 seconds immediately prior to use.48 Clean inhaler every 7 days by wiping mouthpiece with a dry cloth.48

After inhalation, rinse mouth and spit out water.48

Use actuator supplied with the product to administer formoterol in fixed combination with budesonide.48

Dosage

Available as formoterol fumarate dihydrate; dosage expressed in terms of anhydrous drug salt.1 Available as fixed combination containing formoterol fumarate dihydrate and budesonide; dosage expressed in terms of hydrated drug.48

Each dry-powder capsule contains 12 mcg of formoterol fumarate.1 In vitro, each activation of the Aerolizer inhaler delivered about 10 mcg of drug; however, the precise amount of drug delivered to the lungs depends on factors such as patient’s inspiratory flow.1

Each actuation of the oral aerosol inhaler containing the fixed combination of formoterol fumarate and budesonide (Symbicort) delivers 5.1 mcg of formoterol fumarate dihydrate and 91 or 181 mcg of budesonide from the valve.48 Dosage of the fixed combination is expressed in terms of drug delivered from the mouthpiece; each actuation of the oral aerosol inhaler delivers 4.5 mcg of formoterol fumarate dihydrate and 80 or 160 mcg of budesonide from the actuator per metered spray.48 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.48

Commercially available Symbicort aerosol inhaler delivers 60 metered sprays per 6- or 6.9-g canister and 120 metered sprays per 10.2-g canister.48

Pediatric Patients

Asthma
Oral Inhalation Powder

Children ≥5 years of age and adolescents: 12 mcg (contents of one capsule) twice daily.1 11

Formoterol/Budesonide Fixed-combination Therapy
Oral Inhalation Aerosol

Adolescents ≥12 years of age: 9 mcg of formoterol fumarate dihydrate and 160 or 320 mcg of budesonide (2 inhalations) twice daily; recommended initial dosage is based on patient’s asthma severity.48

If control of asthma is inadequate after 1–2 weeks of therapy at the lower dosage, increasing the strength of the fixed combination (higher strengths contain higher dosages of budesonide only) may provide additional asthma control.48

Exercise-induced Bronchospasm
Oral Inhalation Powder

Children ≥5 years of age and adolescents: 12 mcg (contents of one capsule) administered ≥15 minutes before exercise but not more often than once every 12 hours.1 11

Adults

Asthma
Oral Inhalation Powder

12 mcg (contents of one capsule) twice daily.1 11

Formoterol/Budesonide Fixed-combination Therapy
Oral Inhalation Aerosol

9 mcg of formoterol fumarate dihydrate and 160 or 320 mcg of budesonide (2 inhalations) twice daily; recommended initial dosage is based on patient’s asthma severity.48

If control of asthma is inadequate after 1–2 weeks of therapy at the lower dosage, increasing the strength of the fixed combination (higher strengths contain higher dosages of budesonide only) may provide additional asthma control.48

Exercise-induced Bronchospasm
Oral Inhalation Powder

12 mcg (contents of one capsule) administered ≥15 minutes before exercise but not more often than once every 12 hours.1 11

COPD
Oral Inhalation Powder

12 mcg (contents of one capsule) twice daily.1

Formoterol/Budesonide Fixed-combination Therapy
Oral Inhalation Aerosol

9 mcg of formoterol fumarate dihydrate and 320 mcg of budesonide (2 inhalations) twice daily.48

Lower dosages (i.e., 9 mcg of formoterol fumarate dihydrate and 160 mcg of budesonide twice daily) produced no additional improvement in lung function (e.g., FEV1) and are not recommended.48

Prescribing Limits

Pediatric Patients

Asthma
Oral Inhalation Powder

Children ≥5 years of age and adolescents: Maximum 24 mcg daily (12 mcg every 12 hours).1 11

Formoterol/Budesonide Fixed-combination Therapy
Oral Inhalation Aerosol

Adolescents ≥12 years of age: Maximum 9 mcg of formoterol fumarate dihydrate and 320 mcg of budesonide (2 inhalations) twice daily.48 49

Exercise-induced Bronchospasm
Oral Inhalation Powder

Children ≥5 years of age and adolescents: Maximum 24 mcg daily (12 mcg every 12 hours).1

Adults

Asthma
Oral Inhalation Powder

Maximum 24 mcg daily (12 mcg every 12 hours).1 11

Formoterol/Budesonide Fixed-combination Therapy
Oral Inhalation Aerosol

Maximum 9 mcg of formoterol fumarate dihydrate and 320 mcg of budesonide (2 inhalations) twice daily.48 49

Exercise-induced Bronchospasm
Oral Inhalation Powder

Maximum 24 mcg daily (12 mcg every 12 hours).1

COPD
Oral Inhalation Powder

Maximum 24 mcg daily (12 mcg every 12 hours).1

Formoterol/Budesonide Fixed-combination Therapy
Oral Inhalation Aerosol

Maximum 9 mcg of formoterol fumarate dihydrate and 320 mcg of budesonide (2 inhalations) twice daily.48

Special Populations

The following information addresses dosage of formoterol fumarate in special populations.1 When formoterol fumarate dihydrate is used in fixed combination with budesonide, dosage requirements for budesonide should be considered.48

Hepatic Impairment

Formoterol fumarate: No specific dosage recommendations at this time.1 (See Special Populations under Pharmacokinetics.)

Formoterol fumarate in fixed combination with budesonide: Closely monitor patients with hepatic impairment.48

Renal Impairment

No specific dosage recommendations at this time.1 48

Geriatric Patients

Formoterol fumarate: No specific dosage recommendations at this time.1

Formoterol fumarate in fixed combination with budesonide : No dosage adjustment required.48

Cautions for Formoterol Fumarate

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.1 (See Boxed Warning and also Asthma-related Death under Cautions.)

  • Known hypersensitivity to formoterol or any ingredient in the formulation.1 48

  • Formoterol in fixed combination with budesonide (Symbicort): Contraindicated as primary treatment of status asthmaticus or other acute episodes of asthma or COPD when intensive measures required.48

Warnings/Precautions

Warnings

Use of Fixed Combinations

When used in fixed combination with budesonide, consider the cautions, precautions, contraindications, and interactions associated with budesonide.48

Asthma-related Death

Increased risk of asthma-related death reported with long-acting β2-adrenergic agonists (e.g., formoterol).1 41 48 Data from clinical trials suggest that long-acting β2-adrenergic agonists also increase the risk of asthma-related hospitalization in children and adolescents.1 41 48 (See Boxed Warning.)

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.1 41 Data currently inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma controller therapy mitigates the increased risk of asthma-related death from long-acting β2-adrenergic agonists.1 48

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.1 41

Use formoterol in fixed combination with budesonide 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.48 (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.1 29 30 36 37 38 48 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.1 48 Increased risk of asthma-related death is considered a class effect of the long-acting β2-adrenergic agonists, including formoterol.1 48

No adequate studies conducted to determine whether the rate of death is increased in patients with COPD receiving long-acting β2-adrenergic agonists.1

Acute Exacerbations of Asthma or COPD

Do not initiate formoterol therapy in patients with acutely deteriorating or substantially worsening asthma, which may be life-threatening; fatalities reported with orally inhaled sympathomimetic drugs.1 7 Do not initiate formoterol in fixed combination with budesonide in patients with rapidly deteriorating or potentially life-threatening episodes of asthma or COPD.48

Failure to respond to a previously effective dosage may indicate substantially worsening asthma or destabilization of COPD that requires prompt reevaluation.1 18 48 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).1 6 10 11 Reevaluation of asthma therapy may require dosage adjustment of inhaled corticosteroid or initiation of systemic corticosteroids.1 6 10 11 Do not use extra or increased doses of formoterol in such situations.1

If asthma deteriorates in patients receiving formoterol in fixed combination with budesonide, 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 only), adding additional inhaled corticosteroids, or initiating systemic corticosteroids; do not increase the frequency of administration of formoterol in fixed combination with budesonide.48

Do not use formoterol, alone or in fixed combination with budesonide, to relieve symptoms of acute asthma.1 5 6 8 11 48 Formoterol not studied in patients with acute asthma symptoms; do not use additional doses of the drug in such situations.1 Use a short-acting, inhaled β2-adrenergic agonist intermittently (as needed) for acute symptoms of asthma or COPD.18 31 33 34

When initiating formoterol alone or in fixed combination with budesonide, discontinue regular use (e.g., 4 times daily) of short-acting, inhaled β2-agonists and use only for relief of acute asthma symptoms.1 48

Serious exacerbations of asthma, including fatalities, reported in patients receiving formoterol.1 While most cases occurred in patients with severe or acutely deteriorating asthma, a few events occurred in patients with less severe asthma; contribution of formoterol in these cases not determined.1

Excessive Doses

Possible fatalities and/or serious exacerbations of asthma associated with excessive use of inhaled sympathomimetic drugs.1 48

Patients receiving formoterol alone or in fixed combination with budesonide should not use additional formoterol or other long-acting inhaled β2-adrenergic agonists for any reason.1 48

Concomitant Anti-inflammatory Therapy

Formoterol is not a substitute for inhaled or oral corticosteroids.1 No data available demonstrating clinical anti-inflammatory effects of formoterol expected to substitute for or allow reduction in dosage of corticosteroids.1 6 13 15

Do not discontinue or reduce dosage of corticosteroids when formoterol therapy is initiated.1 In patients already requiring oral or inhaled corticosteroids for treatment of asthma, continue such treatment even if patient feels better as a result of initiating formoterol.1 Changes in corticosteroid dosage recommended only after clinical evaluation.1

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.48

Cardiovascular Effects

Possible clinically important changes in SBP and/or DBP, heart rate, and ECG (e.g., flattening of T wave, prolongation of QTc interval, ST-segment depression) changes.1 7 17 48 May require discontinuance of the drug.1 48 Use with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.1 48

Nervous System Effects

Use with caution in patients with seizure disorders.1 48

Paradoxical Bronchospasm

Possible acute, life-threatening bronchospasm may occur immediately upon inhalation of formoterol.1 48 Discontinue therapy immediately and institute alternative therapy.1 48

Sensitivity Reactions

Immediate hypersensitivity reactions (e.g., anaphylaxis, urticaria, angioedema, rash, bronchospasm) reported.1 48

General Precautions

Metabolic Effects

Possible clinically important changes in blood glucose; possible clinically important decreases in serum potassium.1 48 Hypokalemia is usually transient, not requiring supplementation.1 48

Use with caution in patients with thyrotoxicosis and in those unusually responsive to sympathomimetic amines.1 48

Accidental Oral Ingestion

Adverse effects following inadvertent oral ingestion of formoterol dry-powder capsules for oral inhalation reported in some patients.45 (See Administration under Dosage and Administration.)

Specific Populations

Pregnancy

Category C.1 48

May interfere with uterine contractility.1 Carefully weigh benefit versus risk in labor.1

Lactation

Distributed into milk in rats.1 Not known whether formoterol is distributed into human milk.1 Use with caution in nursing women.1

Formoterol in fixed combination with budesonide: Discontinue nursing or the drug.48

Pediatric Use

Formoterol: Safety and efficacy not established in children <5 years of age.1

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.48 Safety and efficacy in children 6 to <12 years of age with asthma not established.48 (See Bronchospasm in Asthma under Uses.)

Available data suggest that long-acting β2-adrenergic agonists may increase the risk of asthma-related death and hospitalization in children and adolescents.1 (See Boxed Warning and also Asthma-related Death under Cautions.)

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.1 48 (See Geriatric Patients under Dosage and Administration.)

Common Adverse Effects

Patients with asthma: Viral infection,1 bronchitis,1 chest infection,1 dyspnea,1 chest pain,1 tremor (dose-related),1 7 12 dizziness (dose-related),1 insomnia,1 tonsillitis,1 rash,1 dysphonia (dose-related).1

Patients with COPD: Upper respiratory tract infection,1 23 24 bronchitis,23 back pain,1 pharyngitis (dose-related),1 24 chest pain,1 24 sinusitis,1 fever (dose-related),1 leg cramps,1 muscle cramps (dose-related),1 24 anxiety,1 pruritus,1 24 increased sputum (dose-related),1 dry mouth,1 trauma.1

Interactions for Formoterol Fumarate

The following information addresses potential interactions with formoterol.1 When formoterol is used in fixed combination with budesonide, consider interactions associated with budesonide.48 No formal drug interaction studies have been performed to date with the fixed-combination.48

Metabolized in the liver by CYP isoenzymes 2D6, 2C19, 2C9, and 2A6.1 48

Drugs that Prolong QT Interval

Potential pharmacologic interaction (increased risk of ventricular arrhythmias and possible potentiation of formoterol effects on cardiovascular system).1 Use extreme caution during concomitant therapy.1

Specific Drugs

Drug

Interaction

Comments

Antidepressants, tricyclic

Possible potentiation of formoterol effects on cardiovascular system1 48

Extreme caution recommended during concomitant therapy1 48 or within 2 weeks following discontinuance of a tricyclic antidepressant48

β-Adrenergic blocking agents (including ophthalmic agents)

Potential antagonism of pulmonary effects resulting in severe bronchospasm in asthmatic patients1 48

If concomitant therapy required, consider cautious use of cardioselective β-adrenergic blocking agents1 48

Corticosteroids

Potential increased risk of hypokalemia1

Diuretics, non-potassium-sparing

Potential additive hypokalemia and/or ECG changes, especially when recommended β-agonist dose is exceeded1 48

Cautious use recommended1 48

MAO Inhibitors

Possible potentiation of formoterol effects on cardiovascular system1 48

Extreme caution recommended during concomitant therapy1 48 or within 2 weeks following discontinuance of an MAO inhibitor48

Sympathomimetic agents

Potential additive pharmacologic and adverse effects1

Caution recommended for concomitant use of formoterol and sympathomimetic agents administered by any route1

Xanthine derivatives

Potential increased risk of hypokalemia1

Formoterol Fumarate Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following inhalation; peak plasma concentrations usually attained within 5–10 minutes.1 48

Onset

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

Duration

12 hours.1

Distribution

Extent

Distributed into milk in animals.1 Not known if crosses the placenta or distributes into milk in humans.1

Plasma Protein Binding

46–64% bound to plasma proteins; binding to serum albumin is 31–38%.1 48

Elimination

Metabolism

Metabolized in the liver by CYP isoenzymes 2D6, 2C19, 2C9, and 2A6.1 48

Elimination Route

Eliminated in feces (24–34%) and in urine (59–62%).1 48

Half-life

10 hours.1

Special Populations

Possible increased exposure in patients with severe hepatic impairment.48

Stability

Storage

Oral Inhalation

Powder

Prior to dispensing, 2–8°C.1 After dispensing, 20–25°C; protect from heat and moisture.1 44 Do not remove capsules of dry powder from their foil blister package until just before use.44 Discard inhaler and dry powder capsules at 4 months or by date indicated on package, whichever is sooner; use the new inhaler provided with each new prescription.44

Aerosol

20–25°C with mouthpiece down.48

Contents under pressure; do not puncture, use or store near heat or an open flame, or place into a fire or incinerator.48 Exposure to temperatures >49°C may cause canister to burst.48 Discard inhaler when labeled number of inhalations used or within 3 months after removal from foil package.48 Never immerse canister in water to determine amount of drug remaining (“float test”).48

Actions

  • Synthetic sympathomimetic amine.1 6 7 15

  • Long-acting, selective β2-receptor agonist.1 6 7 15 48

  • Stimulates β2-adrenergic receptors with little or no effect on β1-1 6 7 48 or α-adrenergic receptors.7

  • Activates adenyl cyclase and stimulates production of cyclic adenosine-3′,5′-monophosphate (cAMP).1 48 Increased concentrations of cAMP relax bronchial smooth muscle and inhibit release of proinflammatory mast-cell mediators (e.g., histamine, leukotrienes).1 48

  • Inhibits allergen-induced infiltration of eosinophils into airways and reduces extravasation of plasma proteins (e.g., albumin).1 2 7 13 48 Does not possess clinically important anti-inflammatory effects.1 6 13 15

  • Prolonged therapy at greater than recommended dosages may be associated with development of tolerance to the bronchodilatory effects.1 17 48

Advice to Patients

  • When used in fixed combination with budesonide, importance of informing patients of important cautionary information about budesonide.48

  • A copy of the manufacturer's patient information (medication guide) for formoterol alone or in fixed combination with budesonide must be provided to all patients with each prescription of the drug.1 40 42 44 48 Importance of instructing patients to read the medication guide prior to initiation of therapy and each time prescription is refilled.1 42 44 48

  • Importance of informing patients that long-acting β2-adrenergic agonists, including formoterol, increase risk of asthma-related death and may increase risk of asthma-related hospitalization in children and adolescents.1 48

  • Importance of informing patients that formoterol should not be the only therapy used for asthma treatment and must only be used as additional therapy when long-term asthma controller therapy (e.g., inhaled corticosteroids) does not adequately control symptoms.1 Importance of informing patients that long-term asthma controller drugs must be continued when formoterol is added to the treatment regimen.1

  • Importance of children receiving therapy under adult supervision.44

  • Importance of adequate understanding of proper storage, preparation, and use of inhalation delivery systems (Foradil Aerolizer or Symbicort).1 11 48

  • Importance of correct procedure for administering formoterol-containing therapy and concomitant therapy (e.g., a short-acting β2-adrenergic agonist).1 11 48 Importance of not breathing into inhaler.1 44

  • Advise patients not to swallow formoterol dry-powder capsules; not to use formoterol dry-powder capsules with any other capsule inhaler; not to use the Aerolizer inhaler with any other capsules; never place capsules into inhaler mouthpiece.44

  • Importance of adherence to dosing schedules of formoterol alone or in fixed combination with budesonide and any concomitant therapy, including not altering the dose or frequency of use of such drugs unless otherwise instructed by a clinician.1 11 48

  • Importance of advising patients that if a dose of formoterol alone or in fixed combination with budesonide is missed, the next dose should be taken at the regularly scheduled time; the dose should not be doubled.44 48

  • 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.1 48

  • Importance of understanding that formoterol-containing therapy does not relieve acute symptoms of asthma or COPD.1 44 48 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 symptoms.1 48

  • 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.1 11 44 48

  • Importance of contacting a clinician if respiratory symptoms worsen or are not relieved by usual dosage of formoterol fumarate.1 11 44 48 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.1 44 48

  • 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 symptoms.1 44 48

  • Importance of advising patients receiving formoterol-containing preparations not to use additional formoterol or other long-acting inhaled β2-adrenergic agonists for any reason.1 48

  • Importance of informing patients not to use formoterol as a substitute for oral or inhaled corticosteroids.1 Importance of patients not discontinuing or altering dosage of corticosteroids without consulting a clinician, even if the patient feels better after initiating formoterol.1

  • Importance of patients not discontinuing formoterol-containing therapy and not discontinuing or reducing concomitant asthma therapy without medical supervision, since symptoms may worsen.1 44 48

  • Importance of administering formoterol ≥15 minutes prior to exercise for prevention of exercise-induced bronchospasm.1 11 Importance of not using additional doses for exercise-induced asthma while receiving prolonged therapy (twice daily) with formoterol.1 11 44

  • Importance of promptly contacting clinicians or seeking emergency medical care if symptoms of a serious allergic reaction (e.g., rash, hives, swelling of the face, tongue or mouth, breathing problems) develop.44

  • 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).1 11 44 48

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 11 48

  • Importance of informing patients of other important precautionary information.1 48 (See Cautions.)

Preparations

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

Formoterol Fumarate (Dihydrate)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral Inhalation

Powder for inhalation (contained in capsules)

12 mcg (of formoterol fumarate)

Foradil Aerolizer Inhaler

Merck

Formoterol Fumarate (Dihydrate) Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral Inhalation

Aerosol

4.5 mcg (of formoterol fumarate dihydrate) with Budesonide 80 mcg per metered spray

Symbicort (with hydrofluoroalkane propellant)

AstraZeneca

4.5 mcg (of formoterol fumarate dihydrate) with Budesonide 160 mcg per metered spray

Symbicort (with hydrofluoroalkane propellant)

AstraZeneca

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Dulera 100-5MCG/ACT Aerosol (SCHERING): 13/$222.98 or 39/$648.96

Dulera 200-5MCG/ACT Aerosol (SCHERING): 13/$229.99 or 39/$659.98

Foradil Aerolizer 12MCG Capsules (SCHERING): 60/$175.99 or 180/$499.97

Symbicort 160-4.5MCG/ACT Aerosol (ASTRAZENECA LP): 10/$232.99 or 31/$666.99

Symbicort 80-4.5MCG/ACT Aerosol (ASTRAZENECA LP): 10/$204.98 or 31/$591.99

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 1, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

Only references cited for selected revisions after 1984 are available electronically.

1. Merck & Co., Inc. Foradil (formoterol fumarate) aerolizer inhalation powder prescribing information. Whitehouse Station, NJ; 2011 May.

2. Wallin A, Sandstrom T, Soderberg M et al. The effects of regular inhaled formoterol, budesonide, and placebo on mucosal inflammation and clinical indices in mild asthma. Am J Respir Crit Care Med. 1999; 159:79-86. [IDIS 421471] [PubMed 9872822]

3. National Asthma Education and Prevention Program. Expert panel report II: guidelines for the diagnosis and management of asthma. 1997 Feb.

4. Palmqvist M, Persson G, Lazer L et al. Inhaled dry-powder formoterol and salmeterol in asthmatic patients: onset of action, duration of effect and potency. Eur Respir J. 1997; 10:2484-9. [PubMed 9426083]

5. Boulet LP, Becker A, Berube D et al. Summaryof recommendations from the Canadian Asthma Consensus Report, 1999. CMAJ. 1999; 161(Suppl.11):S1-S12.

6. Moore RH, Khan A, Dickey BF et al. Long-acting inhaled β2-agonists in asthma therapy. Chest. 1998; 113:1095-1108. [IDIS 404630] [PubMed 9554653]

7. Bartow RA, Brogden RN. Formoterol. An update of its pharmacological properties and therapeutic efficacy in the management of asthma. Drugs. 1998; 55:303-22. [PubMed 9506248]

8. GlaxoWellcome. Serevent Diskus (salmeterol xinafoate inhalation powder) prescribing information. Research Triangle Park, NC; 2001 Mar.

9. Beasley R, Pearce N, Crane J et al. β-agonists: what is the evidence that their use increases the risk of asthma morbidity and mortality? J Allergy Clin Immunol. 1999; 103:S18-30. (IDIS 435471)

10. Tattersfield AE, Postma DS, Barnes PJ et al. Exacerbations of asthma: a descriptive study of 425 severe exacerbations. Am J Respir Crit Care Med. 1999; 160:594-9. [IDIS 435571] [PubMed 10430734]

11. Novartis Pharmaceuticals. Foradil (formoterol fumarate) inhalation powder patient instructions for use. East Hanover, NJ; 2001 Feb.

12. Bensch G, Lapidus RJ, Levine BE et al. A randomized, 12-week, double-blind, placebo-controlled study comparing formoterol dry powder inhaler with albuterol metered-dose inhaler. Ann Allergy Asthma Immunol. 2001; 86L19-27. (IDIS 458307)

13. Pauwels RA, Lofdahl CG, Postma DS et al. Effect of inhaled formoterol and budesonide on exacerbations of asthma. N Engl J Med. 1997; 337:1405-11. [IDIS 394992] [PubMed 9358137]

14. Zhang M, Fawcett JP, Kennedy JM et al. Stereoselective glucuronidation of formoterol by human liver microsomes. Br J Clin Pharmacol. 2000; 49:152-7. [PubMed 10671910]

15. Anon. Formoterol (Foradil Aerolizer) for asthma. Med Lett Drugs Ther. 2001; 43:39-40. [PubMed 11353924]

16. Vervloet D, Ekstrom T, Pela R et al. A 6-month comparison between formoterol and salmeterol in patients with reversible obstructive airways disease. Respir Med. 1998; 92:836-42. [PubMed 9850367]

17. Novartis, East Hanover, NJ: Personal communication

18. National Institutes of Health, National Heart, Lung, and Blood Institute. Global Initiative for asthma: global strategy for asthma management and prevention. Bethesda, MD: National Institutes of Health. 2009 Dec. Available from website. Accessed 2010 Sep 23.

19. National Heart, Lung, and Blood Institute/World Health Organization. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Bethesda, MD: National Heart, Lung, and Blood Institute, Global Initiative for Chronic Obstructive Lung Disease, World Health Organization; 2001. Available from website. Accessed Sep. 26, 2002.

20. American Thoracic Society. ATS Statement: Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1995; 152(Suppl):S78-120.

21. Veterans’ Health Administration Department of Veteran Affairs. The pharmacologic management of chronic obstructive pulmonary disease. Washington, DC: Veterans’ Health Administration; 1999 June. Pharmacy Benefits Management No. 99-0012. Available from website. Accessed Sep. 30, 2002.

22. Veterans’ Health Administration, Department of Veterans’ Affairs. VHA/DOD clinical practice guideline for the management of chronic obstructive pulmonary disease: complete summary. Washington, DC: Veterans’ Health Administration; 1999 Aug.

23. Rossi A, Kristufek P, Levine BE et al. Comparison of the efficacy, tolerability, and safety of formoterol dry powder and oral, slow-release theophylline in the treatment of COPD. Chest. 2002; 121:1058-9. [IDIS 480223] [PubMed 11948033]

24. Dahl R, Greefhorst LA, Nowak D. Inhaled formoterol dry powder versus ipratropium bromide in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001; 164:778-84. [IDIS 469771] [PubMed 11549532]

25. Boehringer Ingelheim. Atrovent (ipratropium bromide) inhalation aerosol prescribing information. Ridgefield, CT; 1999 Mar.

26. British Thoracic Society. Guidelines on the management of asthma. Thorax. 1993; 48(2 Suppl):S1-24.

27. National Institutes of Health, National Heart, Lung, and Blood Institute. Global Initiative for asthma: global strategy for asthma management and prevention NHLBI/WHO Workshop Report. Bethesda, MD: National Institutes of Health. 1995 Jan:77-100. NIH/NHLBI Publication No. 95-3659.

28. National Asthma Education and Prevention Program. Expert panel report II: guidelines for the diagnosis and management of asthma. 1997 Feb.

29. Rickard KA. Dear healthcare professional letter regarding important safety information on the use of Serevent in patients with asthma. Rockville, MD: US Food and Drug Administration; 2003 Jan 23.

30. Food and Drug Administration. Study of asthma-drug halted. FDA Talk Paper. Rockville, MD: Food and Drug Administration; 2003 Jan 23.

31. National Asthma Education Program Expert Panel Report. Executive summary: guidelines for the diagnosis and management of asthma—update on selected topics 2002. NIH Publication No. 02-5075. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute; 2002 Jun.

32. ATS/ERS Standards for the diagnosis and management of patients with COPD. New York, NY: American Thoracic Society, European Respiratory Society; 2004. Available from website. Accessed Dec. 8, 2004.

33. O’Donnell DE, Aaron S, Bourbeau J et al. State of the art compendium: Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease. Can Respir J. 2004; 11 (Suppl. B):7B-59B.

34. Celli BR, Macnee W. Standard for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J. 2004; 23:932-46. [PubMed 15219010]

35. National Heart, Lung, and Blood Institute/World Health Organization. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Bethesda, MD: National Heart, Lung, and Blood Institute, Global Initiative for Chronic Obstructive Lung Disease, World Health Organization; 2007 Dec. Available at NIH website. Accessed Jul 27, 2008.

36. GlaxoSmithKline. Advair Diskus (fluticasone propionate/salmeterol xinafoate) inhalation powder prescribing information. Research Triangle Park, NC; 2004 Sep.

37. Lurie P, Wolfe SM. Misleading data analyses in salmeterol (SMART) study. Lancet. 2005; 366:1261-2. [IDIS 541200] [PubMed 16214589]

38. GlaxoSmithKline. GlaxoSmithKline clinical trial register: salmeterol studies. SLGA5011: a double-blind, randomized, placebo-controlled surveillance study of asthma event outcomes in subjects receiving either usual pharmacolotherapy of asthma or usual pharmacotherapy plus salmeterol 42 mcg twice daily. Research Triangle Park, NC. Available from website. Accessed Oct. 11, 2005.

39. Fontana PG, LeClerc JM. Dear healthcare professional letter regarding Foradil (formoterol fumurate) Aerolizer dry powder capsules for inhalation safety update. Dorval, QC: Novartis Pharmaceuticals Canada; 2005 Sep. 7. Available from website. Accessed Oct. 14, 2005.

40. Food and Drug Administration. FDA drug safety communication: New safety requirements for long-acting inhaled asthma medications called long-acting beta-agonists (LABAs). Rockville, MD; 2010 Feb 18. Available from FDA website. Accessed 2010 Jul 7.

41. Food and Drug Administration. FDA drug safety communication: Drug labels now contain updated recommendations on the appropriate use of long-acting inhaled asthma medications called long-acting beta-agonists (LABAs). Rockville, MD; 2010 Jun 2. Available from FDA website. Accessed 2010 Jul 7.

42. Symbicort (budesonide/formoterol fumarate dihydrate) inhalation aerosol risk evaluation and mitigation strategy (REMS). Initial approval 2009 Feb. Revised 2011 Feb. Reference ID: 2906451. Available from FDA website. Accessed 2011 May 24.

43. Food and Drug Administration. Approved risk evaluation and mitigation strategies (REMS). Available from FDA website. Accessed 2011 Apr 20.

44. Merck & Co., Inc. Foradil (formoterol fumarate) aerolizer inhalation powder medication guide. Whitehouse Station, NJ; 2011 Feb.

45. Food and Drug Administration. FDA public health advisory: Important information on correct use of Spiriva and Foradil capsules. Rockville, MD; 2008 Feb 29. Available at FDA website. Accessed 2008 Apr 23.

46. American Thoracic Society and European Respiratory Society. Standards for the diagnosis and management of patients with COPD: patient version. New York, NY: American Thoracic Society, European Respiratory Society; 2004. Available at ATS website. Accessed Aug 20, 2007.

47. National Asthma Education and Prevention Program. Expert panel report III: guidelines for the diagnosis and management of asthma. 2007 Jul. Bethesda, MD: U.S. Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute. Available at NIH website. Accessed Jul 27, 2008.

48. AstraZeneca L.P. Symbicort (budesonide and formoterol fumarate dihydrate) inhalation aerosol prescribing information. Wilmington, DE; 2010 Jun.

49. AstraZeneca L.P,Wilmington, DE: Personal communication

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