FORADIL

Formoterol fumarate inhalation solution is supplied as 2 mL of formoterol fumarate inhalation solution packaged in a 3 mL single-use low-density polyethylene vial and overwrapped in a foil pouch.

Each vial contains 2 mL of a clear, colorless solution composed of formoterol fumarate dihydrate, USP equivalent to 20 mcg of formoterol fumarate in an isotonic, sterile aqueous solution containing sodium chloride, pH adjusted between 4.5 and 5.5 with citric acid monohydrate and trisodium citrate dihydrate.

The active component of formoterol fumarate inhalation solution is formoterol fumarate dihydrate, USP, a racemate.

Formoterol fumarate dihydrate is a beta 2 -adrenergic bronchodilator.

Its chemical name is(±)-2’-Hydroxy-5’-[(R)-1-hydroxy-2-[[(R)-p-methoxy - α -methylphenethyl]amino]ethyl]formanilide fumarate (2:1) (salt), dihydrate; its structural formula is: Formoterol fumarate dihydrate, USP has a molecular weight of 840.91 and its empirical formula is (C 19 H 24 N 2 O 4 ) 2 •C 4 H 4 O 4 •2H 2 O. Formoterol fumarate dihydrate, USP is a white or almost white or slightly yellow powder, which is freely soluble in dimethyl sulphoxide and in acetic acid, soluble in methanol, slightly soluble in 2-propanol, very slightly soluble in water, practically insoluble in acetonitrile and in diethyl ether.

Formoterol fumarate inhalation solution does not require dilution prior to administration by nebulization.

Like all other nebulized treatments, the amount delivered to the lungs will depend on patient factors and the nebulization system used and its performance.

Plus ® nebulizer (with a facemask or mouthpiece) connected to a PRONEB ® Ultra compressor under in vitro conditions, the mean delivered dose from the mouthpiece was approximately 7.3 mcg (37% of label claim).

The mean nebulizer flow rate was 4 LPM and the nebulization time was 9 minutes.

Formoterol fumarate inhalation solution should be administered from a standard jet nebulizer at adequate flow rates via a facemask or mouthpiece. formoterol-str.jpg.

Formetrol is used to treat asthma but only in conjunction with nose-based corticosteroid drugs for patients suffering from treatable obstructive obstructive pulmonary disease, and also patients with night asthma seizures.

• Formetrol is used as a continuous treatment for chronic pulmonary distress among patients with chronic pulmonary obstructive disease.

• In some cases, it may be used to prevent air-dural distress associated with exercise.

It should not be used for asthma patients who take long-lasting corticosteroid drugs if they have asthma symptoms in their control, only if the patient's response is insufficient for corticosteroid.

• It is not used as a single treatment for asthma because it may increase the likelihood of hospitalization due to symptoms of asthma in infants and children.

• Formitrol is not used to treat acute seizures in chronic pulmonary obstructive patients.

• It is used with caution in patients with heart disease and vascular vessels such as hypertension and heart failure, so the rate of heartbeat and blood pressure must be monitored periodically.

• Carefully used at diabetes patients so that blood sugar levels are periodically monitored during the use of puerperium: there are no studies related to the use of phrmetrol during pregnancy but may be used in certain cases determined by the doctor.

Formoterol fumarate is a long-acting, beta 2 -adrenergic receptor agonist (beta 2 -agonist).

Inhaled formoterol fumarate acts locally in the lung as a bronchodilator.

In vitro studies have shown that formoterol has more than 200-fold greater agonist activity at beta 2 -receptors than at beta 1 -receptors.

Although beta 2 -receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta 1 -receptors are the predominant receptors in the heart, there are also beta 2 -receptors in the human heart comprising 10% to 50% of the total beta-adrenergic receptors.

The precise function of these receptors has not been established, but they raise the possibility that even highly selective beta 2 -agonists may have cardiac effects.

The pharmacologic effects of beta 2 -adrenoceptor agonist drugs, including formoterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3', 5'-adenosine monophosphate (cyclic AMP).

Increased cyclic

AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.

In vitro tests show that formoterol is an inhibitor of the release of mast cell mediators, such as histamine and leukotrienes, from the human lung.

Formoterol also inhibits histamine-induced plasma albumin extravasation in anesthetized guinea pigs and inhibits allergen-induced eosinophil influx in dogs with airway hyper-responsiveness.

The relevance of these in vitro and animal findings to humans with COPD is unknown. 12.2 Pharmacodynamics Systemic Safety and Pharmacokinetic / Pharmacodynamic Relationships The major adverse effects of inhaled beta 2 -agonists occur as a result of excessive activation of the systemic beta-adrenergic receptors.

The most common adverse effects in adults include skeletal muscle tremor and cramps, insomnia, tachycardia, decreases in plasma potassium, and increases in plasma glucose.

Changes in serum potassium and serum glucose were evaluated in 12 COPD patients following inhalation of single doses of formoterol fumarate inhalation solution containing and 244 mcg of formoterol fumarate (calculated on an anhydrous basis) in a crossover study.

At 1 hour after treatment with formoterol fumarate inhalation solution, mean (± standard deviation) serum glucose rose 26 ± 30, 29 ± 28, and 38 ± 44 mg/dL, respectively, and was not significantly different from baseline or trough level at 24 hours post-dose.

At 1 hour after dosing with formoterol fumarate inhalation solution 244 mcg, serum potassium fell by 0.68 ± 0.4 mEq/L, and was not different from baseline or trough level at 24 hours post-dose.

Linear pharmacokinetic/pharmacodynamic (PK/PD) relationships between urinary formoterol excretion and decreases in serum potassium, increases in plasma glucose, and increases in heart rate were generally observed with another inhalation formulation of formoterol fumarate and hence would be expected with formoterol fumarate inhalation solution also.

Following single dose administration of 10-fold the recommended clinical dose of the other formoterol fumarate inhalation formulation having comparable exposure to single dose of 244 mcg of formoterol fumarate inhalation solution (approximately 12-fold the recommended clinical dose) in healthy subjects, the formoterol plasma concentration was found to be highly correlated with the reduction in plasma potassium concentration.

Data from this study showed that maximum reductions from baseline in plasma potassium ranged from 0.55 to 1.52 mmol/L with a median maximum reduction of 1.01 mmol/L. Generally, the maximum effect on plasma potassium was noted to 3 hours after peak formoterol plasma concentrations were achieved.

In the dose-ranging study of formoterol fumarate inhalation solution, ECG-determined heart rate increased by a mean of 6 ±3 beats per minute at 6 hours after a single dose of 244 mcg, but was back to predose level at to 24 hours.

The effect of formoterol fumarate inhalation solution on heart rate and cardiac rhythm was studied in a 12-week clinical trial comparing formoterol fumarate inhalation solution to placebo and an active control treatment.

COPD patients, including 105 patients exposed to formoterol fumarate inhalation solution, underwent continuous electrocardiographic (Holter) monitoring during two 24-hour periods (study baseline and after to 12 weeks of treatment).

ECGs were performed pre-dose and at to 3 hours post-dose at study baseline (prior to dosing) and after and 12 weeks of treatment.

Bazett’s and Fridericia’s methods were used to correct the QT interval for heart rate (QTcB and QTcF, respectively).

The mean increase from baseline in

QTcB interval over the 12-week treatment period was ≤ 4.8 msec for formoterol fumarate inhalation solution and ≤ 4.6 msec for placebo.

The percent of patients who experienced a maximum change in QTc greater than 60 msec at any time during the 12-week treatment period was 0% and 1.8% for formoterol fumarate inhalation solution and placebo, respectively, based on Bazett’s correction, and 1.6% and 0.9%, respectively, based on Fridericia’s correction.

QT was reported as an adverse event in 1 (0.8%) patient treated with formoterol fumarate inhalation solution and 2 (1.8%) placebo patients.

No occurrences of atrial fibrillation or ventricular tachycardia were observed during 24-hour Holter monitoring or reported as adverse events in patients treated with formoterol fumarate inhalation solution after the start of dosing.

No increase in supraventricular tachycardia over placebo-treated subjects was observed.

The mean increase in maximum heart rate from baseline to to 12 weeks after the start of dosing was 0.6 beats per minute (bpm) for patients treated with formoterol fumarate inhalation solution twice daily compared to 1.2 bpm for placebo patients.

There were no clinically meaningful differences from placebo in acute or chronic effects on heart rate, including QTcB and QTcF, or cardiac rhythm resulting from treatment with formoterol fumarate inhalation solution.

At an exposure from formoterol fumarate dry powder formulation comparable to approximately 12-fold the recommended dose of formoterol fumarate inhalation solution, a mean maximum increase of pulse rate of 26 bpm was observed 6 hours post dose in healthy subjects.

This study showed that the maximum increase of mean corrected QT interval (QTc) was 25 msec when calculated using Bazett's correction and was 8 msec when calculated using Fridericia's correction.

QTc returned to baseline within to 24 hours post-dose.

Formoterol plasma concentrations were weakly correlated with pulse rate and increase of QTc duration.

The effects on pulse rate and

QTc interval are known pharmacological effects of this class of study drug and were not unexpected at this supratherapeutic formoterol fumarate inhalation dose.

Tachyphylaxis / Tolerance Tolerance to the effects of inhaled beta-agonists can occur with regularly-scheduled, chronic use.

In a placebo-controlled clinical trial in 351 adult patients with COPD, the bronchodilating effect of formoterol fumarate inhalation solution was determined by the FEV 1 area under the curve over 12 hours following dosing on Day and after 12 weeks of treatment.

The effect of formoterol fumarate inhalation solution did not decrease after 12 weeks of twice-daily treatment (Figures and 2). 12.3 Pharmacokinetics Information on the pharmacokinetics of formoterol (dry powder and/or inhalation solution) in plasma and/or urine is available in healthy subjects as well as patients with chronic obstructive pulmonary disease after oral inhalation of doses at and above the therapeutic dose.

Urinary excretion of unchanged formoterol was used as an indirect measure of systemic exposure.

Plasma drug disposition data parallel urinary excretion, and the elimination half-lives calculated for urine and plasma are similar.

Pharmacokinetic properties of formoterol fumarate were evaluated in 12 COPD patients following inhalation of single doses of formoterol fumarate inhalation solution containing and 244 mcg of formoterol fumarate (calculated on an anhydrous basis) and 12 mcg formoterol fumarate dry powder, through 36 hours after single-dose administration.

Formoterol fumarate concentrations in plasma following the and 20 mcg doses of formoterol fumarate inhalation solution and the 12 mcg dose of formoterol fumarate dry powder were undetectable or only detected sporadically at very low concentrations.

Following a single 244 mcg dose of formoterol fumarate inhalation solution (approximately 12 times the recommended clinical dose), formoterol fumarate concentrations were readily measurable in plasma, exhibiting rapid absorption into plasma, and reaching a maximum drug concentration of 72 pg/mL within approximately 12 minutes of dosing.

The mean amount of formoterol excreted unchanged in 24-hour urine following single oral inhalation doses of 10, 20, and 244 mcg formoterol fumarate inhalation solution were found to be 109.7 ng, 349.6 ng, and 3317.5 ng, respectively.

These findings indicate a near dose proportional increase in systemic exposure within the dose range tested.

When 12 mcg of a dry powder formulation of formoterol fumarate was given twice daily to COPD patients by oral inhalation for 12 weeks, the accumulation index, based on the urinary excretion of unchanged formoterol was 1.19 to 1.38.

This suggests some accumulation of formoterol in plasma with multiple dosing.

Although multiple-dose pharmacokinetic data is unavailable from formoterol fumarate inhalation solution, assumption of linear pharmacokinetics allows a reasonable prediction of minimal accumulation based on single-dose pharmacokinetics.

As with many drug products for oral inhalation, it is likely that the majority of the inhaled formoterol fumarate delivered is swallowed and then absorbed from the gastrointestinal tract.

The binding of formoterol to human plasma proteins in vitro was 61% to 64% at concentrations from 0.1 to 100 ng/mL.

Binding to human serum albumin in vitro was 31% to 38% over a range of to 500 ng/mL.

The concentrations of formoterol used to assess the plasma protein binding were higher than those achieved in plasma following inhalation of a single 244 mcg dose of formoterol fumarate inhalation solution.

Formoterol is metabolized primarily by direct glucuronidation at either the phenolic or aliphatic hydroxyl group and O-demethylation followed by glucuronide conjugation at either phenolic hydroxyl groups.

Minor pathways involve sulfate conjugation of formoterol and deformylation followed by sulfate conjugation.

The most prominent pathway involves direct conjugation at the phenolic hydroxyl group.

The second major pathway involves

O-demethylation followed by conjugation at the phenolic 2'-hydroxyl group.

In vitro studies showed that multiple drug-metabolizing enzymes catalyze glucuronidation (UGT1A1, 1A8, 1A9, 2B7 and 2B15 were the most predominant enzymes) and O-demethylation (CYP2D6, CYP2C19, CYP2C9 and CYP2A6) of formoterol.

Formoterol did not inhibit

CYP450 enzymes at therapeutically relevant concentrations.

Some patients may be deficient in

CYP2D6 or 2C19 or both.

Whether a deficiency in one or both of these isozymes results in elevated systemic exposure to formoterol or systemic adverse effects has not been adequately explored.

Following administration of single 10, 20, and 244 mcg formoterol fumarate inhalation solution doses (calculated on an anhydrous basis) delivered via nebulizer in 12 COPD patients, on average, about 1.1% to 1.7% of the dose was excreted in the urine as unchanged formoterol as compared to about 3.4% excreted unchanged following inhal.

Formitrol works on beta receptors where the smooth muscles of the air people, with little effect on heart rate, are a long-acting drug.

Long-acting beta 2 -adrenergic agonists, such as formoterol fumarate, as monotherapy (without an inhaled corticosteroid) for asthma increase the risk of asthma-related events.

Formoterol fumarate is not indicated for the treatment of asthma.

Most common adverse reactions ( > 2% and more common than placebo) are diarrhea, nausea, nasopharyngitis, dry mouth, vomiting, dizziness, and insomnia To report SUSPECTED ADVERSE REACTIONS, contact Micro Labs USA Inc.fda.gov/medwatch. 6.1 Beta 2 -Agonist Adverse Reaction Profile Adverse reactions to formoterol fumarate inhalation solution are expected to be similar in nature to other beta 2 -adrenergic receptor agonists including: angina, hypertension or hypotension, tachycardia, arrhythmias, nervousness, headache, tremor, dry mouth, muscle cramps, palpitations, nausea, dizziness, fatigue, malaise, insomnia, hypokalemia, hyperglycemia, and metabolic acidosis. 6.2 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to formoterol fumarate inhalation solution 20 mcg twice daily by oral inhalation in 586 patients, including 232 exposed for 6 months and 155 exposed for at least 1 year.

Formoterol fumarate inhalation solution was studied in a 12-week, placebo-and active-controlled trial (123 subjects treated with formoterol fumarate inhalation solution) and a 52-week, active-controlled trial (463 subjects treated with formoterol fumarate inhalation solution).

Patients were mostly

Caucasians (88%) between to 90 years old (mean, 64 years old) and had COPD, with a mean FEV of 1.33 L. Patients with significant concurrent cardiac and other medical diseases were excluded from the trials.

Table 1 shows adverse reactions from the 12-week, double-blind, placebo-controlled trial where the frequency was greater than or equal to 2% in the formoterol fumarate inhalation solution group and where the rate in the formoterol fumarate inhalation solution group exceeded the rate in the placebo group.

In this trial, the frequency of patients experiencing cardiovascular adverse events was 4.1% for formoterol fumarate inhalation solution and 4.4% for placebo.

There were no frequently occurring specific cardiovascular adverse events for formoterol fumarate inhalation solution (frequency greater than or equal to 1% and greater than placebo).

The rate of

COPD exacerbations was 4.1% for formoterol fumarate inhalation solution and 7.9% for placebo.

TABLE 1 Number of patients with adverse reactions in the 12-week multiple-dose controlled clinical trial Adverse Reaction Formoterol Fumarate Inhalation Solution 20 mcg Placebo n (%) n (%) Total Patients 123 114 Diarrhea 6 4 Nausea 6 3 Nasopharyngitis 4 2 Dry Mouth 4 2 Vomiting 3 2 Dizziness 3 1 Insomnia 3 0 0 Patients treated with formoterol fumarate inhalation solution 20 mcg twice daily in the 52-week open-label trial did not experience an increase in specific clinically significant adverse events above the number expected based on the medical condition and age of the patients. 6.3 Postmarketing Experience The following adverse reactions have been reported during post-approval use of formoterol fumarate inhalation solution.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Anaphylactic reactions, urticaria, angioedema (presenting as face, lip, tongue, eye, pharyngeal, or mouth edema), rash, and bronchospasm.

The expected signs and symptoms with overdosage of formoterol fumarate inhalation solution are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of any of the signs and symptoms listed under ADVERSE REACTIONS.

Signs and symptoms may include 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, insomnia, hyperglycemia, hypokalemia, and metabolic acidosis.

As with all inhaled sympathomimetic medications, cardiac arrest and even death may be associated with an overdose of formoterol fumarate inhalation solution.

Treatment of overdosage consists of discontinuation of formoterol fumarate inhalation solution 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 formoterol fumarate inhalation solution.

Cardiac monitoring is recommended in cases of overdosage.

For additional information about overdose treatment, call a poison control center.

Use of a

LABA, including formoterol fumarate, without an inhaled corticosteroid is contraindicated in patients with asthma.

Formoterol fumarate is not indicated for the treatment of asthma.

The recommended dose of formoterol fumarate inhalation solution is one 20 mcg unit-dose vial administered twice daily (morning and evening) by nebulization.

A total daily dose greater than 40 mcg is not recommended.

Formoterol fumarate inhalation solution should be administered by the orally inhaled route via a standard jet nebulizer connected to an air compressor.

The safety and efficacy of formoterol fumarate inhalation solution have been established in clinical trials when administered using the PARI-LC Plus ® nebulizer (with a facemask or mouthpiece) and the PRONEB ® Ultra compressor.

The safety and efficacy of formoterol fumarate inhalation solution delivered from non-compressor based nebulizer systems have not been established.

Formoterol fumarate inhalation solution should always be stored in the foil pouch, and only removed IMMEDIATELY BEFORE USE.

Contents of any partially used container should be discarded.

If the recommended maintenance treatment 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.

The drug compatibility (physical and chemical), efficacy, and safety of formoterol fumarate inhalation solution when mixed with other drugs in a nebulizer have not been established.

For oral inhalation only.

One 20 mcg/2 mL vial every 12 hours.

For use with a standard jet nebulizer (with a facemask or mouthpiece) connected to an air compressor.

Formoterol fumarate inhalation solution, 20 mcg/2mL is supplied as clear, colorless sterile solution for nebulization in 3 mL low-density polyethylene unit dose vials.

Each vial is overwrapped in a foil pouch and supplied in cartons as listed below.

Carton of 30 individually wrapped unit dose vials, NDC 42571-463-73 Carton of 60 individually wrapped unit dose vials, NDC 42571-463-62 Storage and Handling: Prior to dispensing to the patient: Store in a refrigerator, 2°C to 8°C (36°F to 46°F).

Protect pouch from light and heat.

After dispensing to the patient

Store in a refrigerator at 2°C to 8°C (36°F to 46°F) and discard when drug expires or store at room temperature, 20°C to 25°C (68°F to 77°F) and discard if not used after 3 months.

Formoterol fumarate inhalation solution should only be administered via a standard jet nebulizer connected to an air compressor with an adequate airflow and equipped with a facemask or mouthpiece.

Vial should always be stored in the foil pouch, and only removed IMMEDIATELY before use.

Do not take by mouth.

Contents of any partially used container should be discarded.

Discard the container and top after use.

Keep out of the reach of children.

There are limited available data with formoterol fumarate inhalation solution use in pregnant women to inform a drug-associated risk of adverse developmental outcomes.

Beta-agonists may interfere with uterine contractility.

In animal reproduction studies, oral administration of formoterol fumarate to pregnant rats and rabbits caused increased fetal malformations (rats and rabbits), decreased fetal weight (rats), and increased neonatal mortality (rats) following administration of doses that produced exposures approximately to 29,000 times the MRHD on a mg/m 2 or AUC basis.

These adverse effects generally occurred at large multiples of the MRHD when formoterol fumarate was administered by the oral route to achieve high systemic exposures.

No effects were observed in a study with rats that received formoterol fumarate by the inhalation route at an exposure approximately 300 times the MRHD.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the

U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is to 4% and to 20%, respectively.

Clinical Considerations Labor or delivery

There are no adequate and well-controlled human studies that have studied the effects of formoterol fumarate inhalation solution during labor and delivery.

Because of the potential for beta-agonists interference with uterine contractility, use of formoterol fumarate inhalation solution during labor should be restricted to those patients in whom the benefits clearly outweigh the risk.

In embryofetal development studies with pregnant rats and rabbits dosed throughout the period of organogenesis, formoterol fumarate did not cause malformations in either species.

However, for pregnant rats dosed throughout organogenesis, formoterol fumarate caused delayed fetal ossification at an exposure approximately 50 times the MRHD (on a mcg/m 2 basis with maternal oral doses of 200 mcg/kg and higher) and decreased fetal weight at an exposure approximately 1,500 times the MRHD (on a mcg/m 2 basis with maternal oral doses of 6,000 mcg/kg and above).

In a pre.

• and post-natal development study with rats dosed during the late stage of pregnancy, formoterol fumarate caused stillbirth and neonatal mortality at an exposure approximately 1,500 times the MRHD (on a mcg/m 2 basis with maternal oral doses of 6,000 mcg/kg and above).

However, no effects were observed in this study at an exposure approximately 50 times the MRHD (on a mcg/m 2 basis with a maternal oral dose of 200 mcg/kg).

In embryofetal development studies, conducted by another testing laboratory, with pregnant rats and rabbits dosed throughout the period of organogenesis, formoterol fumarate was teratogenic in both species.

Umbilical hernia, a malformation, was observed in rat fetuses at exposures approximately 730 times the MRHD (on a mcg/m 2 basis with maternal oral doses of 3,000 mcg/kg/day and above).

Brachygnathia, a skeletal malformation, was observed in rat fetuses at an exposure approximately 3,600 times the MRHD (on a mcg/m 2 basis with a maternal oral dose of 15,000 mcg/kg/day).

In another study with rats, no teratogenic effects were observed with exposures up to approximately 300 times the MRHD (on a mcg/m 2 basis with a maternal inhalation dose of 1,200 mcg/kg/day).

Subcapsular cysts on the liver were observed in rabbit fetuses at an exposure approximately 29,000 times the MRHD (on a mcg/m 2 basis with a maternal oral dose of 60,000 mcg/kg/day).

No teratogenic effects were observed with exposures up to approximately 1,700 times the MRHD (on a mcg/m 2 basis with a maternal oral dose of 3,500 mcg/kg).

Formoterol fumarate inhalation solution is not indicated for use in children.

The safety and effectiveness of formoterol fumarate inhalation solution in pediatric patients have not been established.

The pharmacokinetics of formoterol fumarate has not been studied in pediatric patients.

Of the 586 subjects who received formoterol fumarate inhalation solution in clinical studies, 284 were 65 years and over, while were 75 years and over.

Of the 123 subjects who received formoterol fumarate inhalation solution in the 12-week safety and efficacy trial, 48 (39%) were 65 years of age or older.

No overall differences in safety or effectiveness were observed between these subjects and younger subjects.

Other reported clinical experience has not identified differences in responses between the elderly and younger adult patients, but greater sensitivity of some older individuals cannot be ruled out.

The pharmacokinetics of formoterol fumarate inhalation solution has not been studied in elderly subjects.