formoterol fumarate 12 MCG Inhalant Powder

Details

WARNINGS

ASTHMA RELATED DEATH Long-acting beta 2 -adrenergic agonists, such as formoterol, the active ingredient in FORADIL AEROLIZER, increase the risk of asthma-related death.

Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA.

Because of this risk, use of FORADIL AEROLIZER for the treatment of asthma without concomitant use of a long-term asthma control medication, such as an inhaled corticosteroid, is contraindicated.

Use FORADIL AEROLIZER only as additional therapy for patients with asthma who are currently taking but are inadequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid.

Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g.

discontinue FORADIL AEROLIZER) if possible without loss of asthma control, and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid.

Do not use FORADIL AEROLIZER for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids.

Pediatric and Adolescent Patients Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients.

For pediatric and adolescent patients with asthma who require addition of a LABA to an inhaled corticosteroid, a fixed-dose combination product containing both an inhaled corticosteroid and LABA should ordinarily be considered to ensure adherence with both drugs.

In cases where use of a separate long-term asthma control medication (e.g.

inhaled corticosteroid) and LABA is clinically indicated, appropriate steps must be taken to ensure adherence with both treatment components.

If adherence cannot be assured, a fixed-dose combination product containing both an inhaled corticosteroid and LABA is recommended.

A 28-week, placebo-controlled US study comparing the safety of salmeterol with placebo, each added to usual asthma therapy, showed an increase in asthma-related deaths in patients receiving salmeterol (13/13,176 in patients treated with salmeterol vs.

3/13,179 in patients treated with placebo; RR 4.37, 95% CI 1.25, 15.34).

The increased risk of asthma-related death is considered a class effect of the long-acting beta2-adrenergic agonists, including formoterol.

No study adequate to determine whether the rate of asthma-related death is increased with FORADIL AEROLIZER has been conducted.

Clinical studies with FORADIL AEROLIZER suggested a higher incidence of serious asthma exacerbations in patients who received FORADIL AEROLIZER than in those who received placebo (See ADVERSE REACTIONS).

The sizes of these studies were not adequate to precisely quantify the differences in serious asthma exacerbation rates between treatment groups.

The studies described above enrolled patients with asthma.

No studies have been conducted that were adequate to determine whether the rate of death in patients with COPD is increased by long-acting beta 2 -adrenergic agonists.

FORADIL AEROLIZER should not be initiated in patients with significantly worsening or acutely deteriorating asthma, which may be a life-threatening condition.

The use of FORADIL AEROLIZER in this setting is inappropriate.

FORADIL AEROLIZER should not be used in conjunction with an inhaled, long-acting beta 2 -agonist.

FORADIL AEROLIZER should not be used with other medications containing long-acting beta 2 -agonists.

FORADIL AEROLIZER is not a substitute for inhaled or oral corticosteroids.

Corticosteroids should not be stopped or reduced at the time FORADIL AEROLIZER is initiated.

When beginning treatment with FORADIL AEROLIZER, patients who have been taking inhaled, short-acting beta 2 -agonists on a regular basis (e.g., four times a day) should be instructed to discontinue the regular use of these drugs and use them only for symptomatic relief of acute asthma symptoms .

See PRECAUTIONS, Information for Patients and the accompanying Medication Guide.

Paradoxical Bronchospasm As with other inhaled beta2-agonists, formoterol can produce paradoxical bronchospasm, that may be life-threatening.

If paradoxical bronchospasm occurs, FORADIL AEROLIZER should be discontinued immediately and alternative therapy instituted.

Deterioration of Asthma Asthma may deteriorate acutely over a period of hours or chronically over several days or longer.

It is important to watch for signs of worsening asthma, such as increasing use of inhaled, short-acting beta2-adrenergic agonists or a significant decrease in peak expiratory flow (PEF) or lung function.

Such findings require immediate evaluation.

Patients should be advised to seek immediate attention should their condition deteriorate.

Increasing the daily dosage of FORADIL AEROLIZER beyond the recommended dose in this situation is not appropriate.

FORADIL AEROLIZER should not be used more frequently than twice daily (morning and evening) at the recommended dose.

Use of Anti-inflammatory Agents There are no data demonstrating that FORADIL has any clinical anti-inflammatory effect and therefore it cannot be expected to take the place of corticosteroids.

Patients who require oral or inhaled corticosteroids for treatment of asthma should be continued on this type of treatment even if they feel better as a result of initiating FORADIL AEROLIZER.

Any change in corticosteroid dosage, in particular a reduction, should be made ONLY after clinical evaluation (see PRECAUTIONS, Information for Patients).

Cardiovascular Effects Formoterol fumarate, like other beta2-agonists, can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, blood pressure, and/or symptoms.

Although such effects are uncommon after administration of FORADIL AEROLIZER at recommended doses, if they occur, the drug may need to be discontinued.

In addition, beta-agonists have been reported to produce ECG changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression.

The clinical significance of these findings is unknown.

Therefore, formoterol fumarate, like other sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension (see PRECAUTIONS, General).

Immediate Hypersensitivity Reactions Immediate hypersensitivity reactions may occur after administration of FORADIL AEROLIZER, as demonstrated by cases of anaphylactic reactions, urticaria, angioedema, rash, and bronchospasm.

Do Not Exceed Recommended Dose Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma.

The exact cause of death is unknown, but cardiac arrest following an unexpected development of a severe acute asthmatic crisis and subsequent hypoxia is suspected.

In addition, data from clinical trials with FORADIL AEROLIZER suggest that the use of doses higher than recommended is associated with an increased risk of serious asthma exacerbations (see ADVERSE REACTIONS).

OVERDOSAGE

The expected signs and symptoms with overdosage of FORADIL AEROLIZER are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of any of the signs and symptoms listed under ADVERSE REACTIONS, e.g., angina, hypertension or hypotension, tachycardia, with rates up to 200 beats/min., arrhythmias, nervousness, headache, tremor, seizures, muscle cramps, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, hypokalemia, hyperglycemia, and insomnia.

Metabolic acidosis may also occur.

As with all inhaled sympathomimetic medications, cardiac arrest and even death may be associated with an overdose of FORADIL AEROLIZER.

Treatment of overdosage consists of discontinuation of FORADIL AEROLIZER together with institution of appropriate symptomatic and/or supportive therapy.

The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm.

There is insufficient evidence to determine if dialysis is beneficial for overdosage of FORADIL AEROLIZER.

Cardiac monitoring is recommended in cases of overdosage.

The minimum acute lethal inhalation dose of formoterol fumarate in rats is 156 mg/kg (approximately 53,000 and 25,000 times the maximum recommended daily inhalation dose in adults and children, respectively, on a mg/m2 basis).

The median lethal oral doses in Chinese hamsters, rats, and mice provide even higher multiples of the maximum recommended daily inhalation dose in humans.

DESCRIPTION

FORADIL® AEROLIZER® consists of a capsule dosage form containing a dry powder formulation of FORADIL (formoterol fumarate) intended for oral inhalation only with the AEROLIZER Inhaler.

Each clear, hard gelatin capsule contains a dry powder blend of 12 mcg of formoterol fumarate and 25 mg of lactose (which contains trace levels of milk proteins) as a carrier.

The active component of FORADIL is formoterol fumarate, a racemate.

Formoterol fumarate is a selective beta2-adrenergic bronchodilator.

Its chemical name is (±)-2-hydroxy-5-[(1RS)-1-hydroxy-2-[[(1RS)-2-(4-methoxyphenyl)-1-methylethyl]-amino]ethyl]formanilide fumarate dihydrate; its structural formula is Formoterol fumarate has a molecular weight of 840.9, and its empirical formula is (C19H24N2O4)2•C4H4O4•2H2O.

Formoterol fumarate is a white to yellowish crystalline powder, which is freely soluble in glacial acetic acid, soluble in methanol, sparingly soluble in ethanol and isopropanol, slightly soluble in water, and practically insoluble in acetone, ethyl acetate, and diethyl ether.

The AEROLIZER Inhaler is a plastic device used for inhaling FORADIL.

The amount of drug delivered to the lung will depend on patient factors, such as inspiratory flow rate and inspiratory time.

Under standardized in vitro testing at a fixed flow rate of 60 L/min for 2 seconds, the AEROLIZER Inhaler delivered 10 mcg of formoterol fumarate from the mouthpiece.

Peak inspiratory flow rates (PIFR) achievable through the AEROLIZER Inhaler were evaluated in 33 adult and adolescent patients and 32 pediatric patients with mild-to-moderate asthma.

Mean PIFR was 117.82 L/min (range 34-188 L/min) for adult and adolescent patients, and 99.66 L/min (range 43-187 L/min) for pediatric patients.

Approximately ninety percent of each population studied generated a PIFR through the device exceeding 60 L/min.

To use the delivery system, a FORADIL capsule is placed in the well of the AEROLIZER Inhaler, and the capsule is pierced by pressing and releasing the buttons on the side of the device.

The formoterol fumarate formulation is dispersed into the air stream when the patient inhales rapidly and deeply through the mouthpiece.

formoterol fumarate structural formula

CLINICAL STUDIES

CLINICAL TRIALS Figures 1a and 1b: Mean FEV1 from Clinical Trial A Figures 1a and 1b: Mean FEV1 from Clinical Trial A Figures 2a and 2b: Mean FEV1 from Clinical Trial B Figures 2a and 2b: Mean FEV1 from Clinical Trial B Figure 3 Mean FEV1 after 12 Weeks of treatment from COPD Trial A Adolescent and Adult Asthma Trials In a placebo-controlled, single-dose clinical trial, the onset of bronchodilation (defined as a 15% or greater increase from baseline in FEV1) was similar for FORADIL AEROLIZER and albuterol 180 mcg by metered-dose inhaler.

In single-dose and multiple-dose clinical trials, the maximum improvement in FEV1 for FORADIL AEROLIZER 12 mcg generally occurred within 1 to 3 hours, and an increase in FEV1 above baseline was observed for 12 hours in most patients.

FORADIL AEROLIZER 12 mcg twice daily was compared to FORADIL AEROLIZER 24 mcg twice daily, albuterol 180 mcg four times daily by metered-dose inhaler, and placebo in a total of 1095 adult and adolescent patients 12 years of age and above with mild-to-moderate asthma (defined as FEV1 40%-80% of the patient’s predicted normal value) who participated in two pivotal, 12-week, multi-center, randomized, double-blind, parallel group studies.

The results of both studies showed that FORADIL AEROLIZER 12 mcg twice daily resulted in significantly greater post-dose bronchodilation (as measured by serial FEV1 for 12 hours post-dose) throughout the 12-week treatment period.

There was no significant difference in post-dose bronchodilation between FORADIL AEROLIZER 12 mcg twice daily and FORADIL AEROLIZER 24 mcg twice daily, but serious asthma exacerbations occurred more commonly in the higher dose group (see WARNINGS and ADVERSE REACTIONS).

Mean FEV1 measurements from both studies are shown below for the first and last treatment days (see Figures 1 and 2).

Figures 1a and 1b: Mean FEV1 from Clinical Trial A Figures 1a and 1b: Mean FEV1 from Clinical Trial A Figures 2a and 2b: Mean FEV1 from Clinical Trial B Figures 2a and 2b: Mean FEV1 from Clinical Trial B Compared with placebo and albuterol, patients treated with FORADIL AEROLIZER 12 mcg demonstrated improvement in many secondary efficacy endpoints, including improved combined and nocturnal asthma symptom scores, fewer nighttime awakenings, fewer nights in which patients used rescue medication, and higher morning and evening peak flow rates.

FORADIL AEROLIZER 24 mcg twice daily did not provide any additional improvements in these secondary endpoints compared to FORADIL AEROLIZER 12 mcg twice daily.

A 16-week, randomized, multi-center, double-blind, parallel-group study enrolled 1568 patients 12 years of age and older with mild-to-moderate asthma (defined as FEV1 ≥40% of the patient’s predicted normal value) in three treatment groups: FORADIL AEROLIZER 12 mcg twice daily, FORADIL AEROLIZER 24 mcg twice daily, and placebo.

The study’s primary endpoint was the incidence of serious asthma-related adverse events.

Serious asthma exacerbations occurred in 3 (0.6%) patients who received FORADIL AEROLIZER 12 mcg twice daily, 2 (0.4%) patients who received FORADIL AEROLIZER 24 mcg twice daily, and 1 (0.2%) patient who received placebo.

The size of this study was not adequate to precisely quantify the differences in serious asthma exacerbation rates between treatment groups.

All serious asthma exacerbations resulted in hospitalizations.

While there were no deaths in the study, the duration and size of this study were not adequate to quantify the rate of asthma-related death.

See WARNINGS for information about a study which compared another long-acting beta2-adrenergic agonist to placebo.

Pediatric Asthma Trial A 12-month, multi-center, randomized, double-blind, parallel-group, study compared FORADIL AEROLIZER 12 mcg twice daily and FORADIL AEROLIZER 24 mcg twice daily to placebo in a total of 518 children with asthma (ages 5-12 years) who required daily bronchodilators and anti-inflammatory treatment.

Efficacy was evaluated on the first day of treatment, at Week 12, and at the end of treatment.

FORADIL AEROLIZER 12 mcg twice daily demonstrated a greater 12-hour FEV1 AUC compared to placebo on the first day of treatment, after twelve weeks of treatment, and after one year of treatment.

FORADIL AEROLIZER 24 mcg twice daily did not result in any additional improvement in 12-hour FEV1 AUC compared to FORADIL AEROLIZER 12 mcg twice daily.

Exercise-Induced Bronchospasm Trials The effect of FORADIL AEROLIZER on exercise-induced bronchospasm (defined as >20% fall in FEV1) was examined in four randomized, single-dose, double-blind, crossover studies in a total of 77 patients 4 to 41 years of age with exercise-induced bronchospasm.

Exercise challenge testing was conducted 15 minutes, and 4, 8, and 12 hours following administration of a single dose of study drug (FORADIL AEROLIZER 12 mcg, albuterol 180 mcg by metered-dose inhaler, or placebo) on separate test days.

FORADIL AEROLIZER 12 mcg and albuterol 180 mcg were each superior to placebo for FEV1 measurements obtained 15 minutes after study drug administration.

FORADIL AEROLIZER 12 mcg maintained superiority over placebo at 4, 8, and 12 hours after administration.

Most subjects were protected from exercise-induced bronchospasm for up to 12 hours following administration of FORADIL AEROLIZER; however, some were not.

The efficacy of FORADIL AEROLIZER in the prevention of exercise-induced bronchospasm when dosed on a regular twice daily regimen has not been studied.

Adult COPD Trials In multiple-dose clinical trials in patients with COPD, FORADIL AEROLIZER 12 mcg was shown to provide onset of significant bronchodilation (defined as 15% or greater increase from baseline in FEV1) within 5 minutes of oral inhalation after the first dose.

Bronchodilation was maintained for at least 12 hours.

FORADIL AEROLIZER was studied in two pivotal, double-blind, placebo-controlled, randomized, multi-center, parallel-group trials in a total of 1634 adult patients (age range: 34-88 years; mean age: 63 years) with COPD who had a mean FEV1 that was 46% of predicted.

The diagnosis of COPD was based upon a prior clinical diagnosis of COPD, a smoking history (greater than 10 pack-years), age (at least 40 years), spirometry results (prebronchodilator baseline FEV1 less than 70% of the predicted value, and at least 0.75 liters, with the FEV1/VC being less than 88% for men and less than 89% for women), and symptom score (greater than zero on at least four of the seven days prior to randomization).

These studies included approximately equal numbers of patients with and without baseline bronchodilator reversibility, defined as a 15% or greater increase FEV1 after inhalation of 200 mcg of albuterol sulfate.

A total of 405 patients received FORADIL AEROLIZER 12 mcg, administered twice daily.

Each trial compared FORADIL AEROLIZER 12 mcg twice daily and FORADIL AEROLIZER 24 mcg twice daily with placebo and an active control drug.

The active control drug was ipratropium bromide in COPD Trial A, and slow-release theophylline in COPD Trial B (the theophylline arm in this study was open-label).

The treatment period was 12 weeks in COPD Trial A, and 12 months in COPD Trial B.

The results showed that FORADIL AEROLIZER 12 mcg twice daily resulted in significantly greater post-dose bronchodilation (as measured by serial FEV1 for 12 hours post-dose; the primary efficacy analysis) compared to placebo when evaluated after 12 weeks of treatment in both trials, and after 12 months of treatment in the 12-month trial (COPD Trial B).

Compared to FORADIL AEROLIZER 12 mcg twice daily, FORADIL AEROLIZER 24 mcg twice daily did not provide any additional benefit on a variety of endpoints including FEV1.

Mean FEV1 measurements after 12 weeks of treatment for one of the two major efficacy studies are shown in the figure below.

Figure 3 Mean FEV1 after 12 Weeks of treatment from COPD Trial A FORADIL AEROLIZER 12 mcg twice daily was statistically superior to placebo at all post-dose timepoints tested (from 5 minutes to 12 hours post-dose) throughout the 12-week (COPD Trial A) and 12-month (COPD Trial B) treatment periods.

In both pivotal trials compared with placebo, patients treated with FORADIL AEROLIZER 12 mcg demonstrated improved morning pre-medication peak expiratory flow rates and took fewer puffs of rescue albuterol.

HOW SUPPLIED

FORADIL AEROLIZER contains: aluminum blister-packaged 12-mcg FORADIL (formoterol fumarate) clear gelatin capsules with “CG” printed on one end and “FXF” printed on the opposite end; one AEROLIZER Inhaler; and Medication Guide.

Unit Dose (blister pack) Box of 60 (strips of 6).

NDC 54868-4972-1 FORADIL capsules should be used with the AEROLIZER Inhaler only.

The AEROLIZER Inhaler should not be used with any other capsules.

Prior to dispensing: Store in a refrigerator, 2°C-8°C (36°F-46°F) After dispensing to patient: Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature].

Protect from heat and moisture.

CAPSULES SHOULD ALWAYS BE STORED IN THE BLISTER AND ONLY REMOVED FROM THE BLISTER IMMEDIATELY BEFORE USE.

Always discard the FORADIL capsules and AEROLIZER Inhaler by the “Use by” date and always use the new AEROLIZER Inhaler provided with each new prescription.

Keep out of the reach of children.

Manufactured by: Novartis Pharma AG, Basle, Switzerland Distributed by: Schering Corporation, a subsidiary of MERCK & CO., INC.

May 2011 Additional barcode labeling by: Physicians Total Care, Inc.

Tulsa, Oklahoma 74146

INDICATIONS AND USAGE

Asthma FORADIL AEROLIZER is indicated for the treatment of asthma and in the prevention of bronchospasm only as concomitant therapy with a long-term asthma control medication, such as an inhaled corticosteroid, in adults and children 5 years of age and older with reversible obstructive airways disease, including patients with symptoms of nocturnal asthma.

Long-acting beta2-adrenergic agonists (LABA), such as formoterol, the active ingredient in FORADIL AEROLIZER, increase the risk of asthma-related death (see WARNINGS).

Use of FORADIL AEROLIZER for the treatment of asthma without concomitant use of a long-term asthma control medication, such as an inhaled corticosteroid, is contraindicated.

Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g.

discontinue FORADIL AEROLIZER) if possible without loss of asthma control, and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid.

Do not use FORADIL AEROLIZER for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids.

Pediatric and Adolescent Patients Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients (see WARNINGS).

In cases where use of a separate long-term asthma control medication (e.g.

inhaled corticosteroid) and LABA is clinically indicated, appropriate steps must be taken to ensure adherence with both treatment components.

If adherence cannot be assured, a fixed-dose combination product containing both an inhaled corticosteroid and LABA is recommended.

Exercise-Induced Bronchospasm FORADIL AEROLIZER is also indicated for the acute prevention of exercise-induced bronchospasm (EIB) in adults and children 5 years of age and older, when administered on an occasional, as-needed basis.

Use of FORADIL AEROLIZER as a single agent for the prevention of exercise-induced bronchospasm may be clinically indicated in patients who do not have persistent asthma.

In patients with persistent asthma, use of FORADIL AEROLIZER for the prevention of exercise-induced bronchospasm may be clinically indicated, but the treatment of asthma should include a long-term asthma control medication, such as an inhaled corticosteroid.

Chronic Obstructive Pulmonary Disease FORADIL AEROLIZER is indicated for the long-term, twice daily (morning and evening) administration in the maintenance treatment of bronchoconstriction in patients with Chronic Obstructive Pulmonary Disease including chronic bronchitis and emphysema.

BOXED WARNING

WARNING: ASTHMA RELATED DEATH Long-acting beta 2 -adrenergic agonists (LABA), such as formoterol the active ingredient in FORADIL AEROLIZER, increase the risk of asthma-related death.

Data from a large placebo-controlled US study that compared the safety of another LABA (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol.

This finding with salmeterol is considered a class effect of LABA, including formoterol (see WARNINGS).

Because of this risk, use of FORADIL AEROLIZER for the treatment of asthma without a concomitant long-term asthma control medication, such as an inhaled corticosteroid, is contraindicated.

Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g.

discontinue FORADIL AEROLIZER) if possible without loss of asthma control, and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid.

Do not use FORADIL AEROLIZER for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids.

Pediatric and Adolescent Patients Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients.

In cases where use of a separate long-term asthma control medication (e.g.

inhaled corticosteroid) and LABA is clinically indicated, appropriate steps must be taken to ensure adherence with both treatment components.

If adherence cannot be assured, a fixed-dose combination product containing both an inhaled corticosteroid and LABA is recommended.

DOSAGE AND ADMINISTRATION

FORADIL capsules should be administered only by the oral inhalation route and only using the AEROLIZER Inhaler (see the accompanying Medication Guide).

FORADIL capsules should not be ingested (i.e., swallowed) orally .

FORADIL capsules should always be stored in the blister, and only removed IMMEDIATELY BEFORE USE.

Treatment of Asthma Long-acting beta2-adrenergic agonists (LABA), such as formoterol, the active ingredient in FORADIL AEROLIZER, increase the risk of asthma-related death (see Warnings).

Because of this risk, use of FORADIL AEROLIZER for the treatment of asthma without concomitant use of a long-term asthma control medication, such as an inhaled corticosteroid, is contraindicated.

Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g.

discontinue FORADIL AEROLIZER) if possible without loss of asthma control, and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid.

Do not use FORADIL AEROLIZER for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids.

Pediatric and Adolescent Patients Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients.

For patients with asthma less than 18 years of age who require addition of a LABA to an inhaled corticosteroid, a fixed-dose combination product containing both an inhaled corticosteroid and LABA should ordinarily be used to ensure adherence with both drugs.

In cases where use of a separate long-term asthma control medication (e.g.

inhaled corticosteroid) and LABA is clinically indicated, appropriate steps must be taken to ensure adherence with both treatment components.

If adherence cannot be assured, a fixed-dose combination product containing both an inhaled corticosteroid and LABA is recommended.

For adults and children 5 years of age and older, the usual dosage is the inhalation of the contents of one 12-mcg FORADIL capsule every 12 hours using the AEROLIZER Inhaler.

The patient must not exhale into the device.

The total daily dose of FORADIL should not exceed one capsule twice daily (24 mcg total daily dose).

More frequent administration or administration of a larger number of inhalations is not recommended.

If symptoms arise between doses, an inhaled short-acting beta2-agonist should be taken for immediate relief.

If a previously effective dosage regimen fails to provide the usual response, medical advice should be sought immediately as this is often a sign of destabilization of asthma.

Under these circumstances, the therapeutic regimen should be re-evaluated.

For Prevention of Exercise-Induced Bronchospasm (EIB) Use of FORADIL AEROLIZER as a single agent for the prevention of exercise-induced bronchospasm may be clinically indicated in patients who do not have persistent asthma.

For adults and children 5 years of age or older, the usual dosage is the inhalation of the contents of one 12-mcg FORADIL capsule at least 15 minutes before exercise administered on an occasional as needed basis.

When used intermittently as needed for prevention, protection may last up to 12 hours.

Additional doses of FORADIL AEROLIZER should not be used for 12 hours after the administration of this drug.

Regular, twice-daily dosing has not been studied in preventing EIB.

Patients who are receiving FORADIL AEROLIZER twice daily for treatment of their asthma should not use additional doses for prevention of EIB and may require a short-acting bronchodilator.

For Maintenance Treatment of Chronic Obstructive Pulmonary Disease (COPD) The usual dosage is the inhalation of the contents of one 12 mcg FORADIL capsule every 12 hours using the AEROLIZER inhaler.

A total daily dose of greater than 24 mcg is not recommended.

If a previously effective dosage regimen fails to provide the usual response, medical advice should be sought immediately as this is often a sign of destabilization of COPD.

Under these circumstances, the therapeutic regimen should be re-evaluated and additional therapeutic options should be considered.