Fluticasone Propionate And Salmeterol DISKUS

Individual patients will experience a variable time to onset and degree of symptom relief. For patients who do not respond adequately to the starting dosage after 2 weeks of therapy, replacing the current strength of Fluticasone Propionate/Salmeterol DISKUS with a higher strength may provide additional improvement in asthma control.

, replacing the current strength of Fluticasone Propionate/Salmeterol DISKUS with a higher strength, adding additional ICS, initiating oral corticosteroids) should be considered. Pediatric Patients Aged 4 to 11 Years For patients with asthma aged 4 to 11 years who are not controlled on an ICS, the dosage is 1 inhalation of Fluticasone Propionate/Salmeterol DISKUS inhalation powder 100/50 mcg twice daily, approximately 12 hours apart.

2 Chronic Obstructive Pulmonary Disease The recommended dosage for patients with COPD is 1 inhalation of Fluticasone Propionate/Salmeterol DISKUS inhalation powder 250/50 mcg twice daily, approximately 12 hours apart. If shortness of breath occurs in the period between doses, an inhaled, short-acting beta 2 -agonist should be taken for immediate relief.

S. trial of 12 weeks’ treatment duration. A total of 203 subjects (74 females and 129 males) who were receiving ICS at trial entry were randomized to either fluticasone propionate/salmeterol DISKUS 100/50 mcg or fluticasone propionate inhalation powder 100 mcg twice daily.

Common adverse reactions (≥3% and greater than placebo) seen in the pediatric subjects but not reported in the adult and adolescent clinical trials include: throat irritation and ear, nose, and throat infections. Laboratory Test Abnormalities Elevation of hepatic enzymes was reported in ≥1% of subjects in clinical trials.

The elevations were transient and did not lead to discontinuation from the trials. In addition, there were no clinically relevant changes noted in glucose or potassium. 2 Clinical Trials Experience in Chronic Obstructive Pulmonary Disease Short-term (6 Months to 1 Year) Trials The short-term safety data are based on exposure to fluticasone propionate/salmeterol DISKUS 250/50 mcg twice daily in one 6-month and two 1-year clinical trials.

In the 6-month trial, a total of 723 adult subjects (266 females and 457 males) were treated twice daily with fluticasone propionate/salmeterol DISKUS 250/50 mcg, fluticasone propionate inhalation powder 250 mcg, salmeterol inhalation powder, or placebo.

The mean age of the subjects was 64, and the majority (93%) was Caucasian. In this trial, 70% of the subjects treated with fluticasone propionate/salmeterol DISKUS reported an adverse reaction compared with 64% on placebo. 6 days for placebo.

The incidence of adverse reactions in the 6-month trial is shown in Table 3 . Table 3. Overall Adverse Reactions with Fluticasone Propionate/Salmeterol DISKUS 250/50 mcg with ≥3% Incidence in Subjects with Chronic Obstructive Pulmonary Disease Associated with Chronic Bronchitis Adverse Event Fluticasone Propionate/ Salmeterol DISKUS 250/50 mcg (n = 178) % Fluticasone Propionate 250 mcg (n = 183) % Salmeterol 50 mcg (n = 177) % Placebo (n = 185) % Ear, nose, and throat Candidiasis mouth/throat 10 6 3 1 Throat irritation 8 5 4 7 Hoarseness/dysphonia 5 3 <1 0 Sinusitis 3 8 5 3 Lower respiratory Viral respiratory infections 6 4 3 3 Neurology Headaches 16 11 10 12 Dizziness 4 <1 3 2 Non-site specific Fever 4 3 0 3 Malaise and fatigue 3 2 2 3 Musculoskeletal Musculoskeletal pain 9 8 12 9 Muscle cramps and spasms 3 3 1 1 In the two 1-year trials, fluticasone propionate/salmeterol DISKUS 250/50 mcg was compared with salmeterol in 1,579 subjects (863 males and 716 females).

The mean age of the subjects was 65 years, and the majority (94%) was Caucasian. To be enrolled, all of the subjects had to have had a COPD exacerbation in the previous 12 months. In this trial, 88% of the subjects treated with fluticasone propionate/salmeterol DISKUS and 86% of the subjects treated with salmeterol reported an adverse event.

The most common events that occurred with a frequency of >5% and more frequently in the subjects treated with fluticasone propionate/salmeterol DISKUS were nasopharyngitis, upper respiratory tract infection, nasal congestion, back pain, sinusitis, dizziness, nausea, pneumonia, candidiasis, and dysphonia.

Overall, 55 (7%) of the subjects treated with fluticasone propionate/salmeterol DISKUS and 25 (3%) of the subjects treated with salmeterol developed pneumonia. The incidence of pneumonia was higher in subjects older than 65 years, 9% in the subjects treated with fluticasone propionate/salmeterol DISKUS compared with 4% in the subjects treated with fluticasone propionate/salmeterol DISKUS younger than 65 years.

In the subjects treated with salmeterol, the incidence of pneumonia was the same (3%) in both age groups. ] Long-term (3 Years) Trial The safety of fluticasone propionate/salmeterol DISKUS 500/50 mcg was evaluated in a randomized, double-blind, placebo-controlled, multicenter, international, 3-year trial in 6,184 adult subjects with COPD (4,684 males and 1,500 females).

The mean age of the subjects was 65 years, and the majority (82%) was Caucasian. The distribution of adverse events was similar to that seen in the 1-year trials with fluticasone propionate/salmeterol DISKUS 250/50 mcg. In addition, pneumonia was reported in a significantly increased number of subjects treated with fluticasone propionate/salmeterol DISKUS 500/50 mcg and fluticasone propionate 500 mcg (16% and 14%, respectively) compared with subjects treated with salmeterol 50 mcg or placebo (11% and 9%, respectively).

When adjusted for time on treatment, the rates of pneumonia were 84 and 88 events per 1,000 treatment-years in the groups treated with fluticasone propionate 500 mcg and with fluticasone propionate/salmeterol DISKUS 500/50 mcg, respectively, compared with 52 events per 1,000 treatment-years in the salmeterol and placebo groups.

Similar to what was seen in the 1-year trials with fluticasone propionate/salmeterol DISKUS 250/50 mcg, the incidence of pneumonia was higher in subjects older than 65 years (18% with fluticasone propionate/salmeterol DISKUS 500/50 mcg versus 10% with placebo) compared with subjects younger than 65 years (14% with fluticasone propionate/salmeterol DISKUS 500/50 mcg versus 8% with placebo).

] Additional Adverse Reactions Other adverse reactions not previously listed, whether considered drug-related or not by the investigators, that were reported more frequently by subjects with COPD treated with fluticasone propionate/salmeterol DISKUS compared with subjects treated with placebo include the following: syncope; ear, nose, and throat infections; ear signs and symptoms; laryngitis; nasal congestion/blockage; nasal sinus disorders; pharyngitis/throat infection; hypothyroidism; dry eyes; eye infections; gastrointestinal signs and symptoms; oral lesions; abnormal liver function tests; bacterial infections; edema and swelling; viral infections.

Laboratory Abnormalities There were no clinically relevant changes in these trials. Specifically, no increased reporting of neutrophilia or changes in glucose or potassium was noted. 3 Postmarketing Experience In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postapproval use of any formulation of fluticasone propionate/salmeterol, fluticasone propionate, and/or salmeterol regardless of indication.

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. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to fluticasone propionate/salmeterol DISKUS, fluticasone propionate, and/or salmeterol or a combination of these factors.

Cardiac Disorders Arrhythmias (including atrial fibrillation, extrasystoles, supraventricular tachycardia), ventricular tachycardia. Endocrine Disorders Cushing’s syndrome, Cushingoid features, growth velocity reduction in children/adolescents, hypercorticism.

Eye Disorders Glaucoma. Gastrointestinal Disorders Abdominal pain, dyspepsia, xerostomia. Immune System Disorders Immediate and delayed hypersensitivity reaction (including very rare anaphylactic reaction). Very rare anaphylactic reaction in patients with severe milk protein allergy.

Infections and Infestations Esophageal candidiasis. Metabolic and Nutrition Disorders Hyperglycemia, weight gain. Musculoskeletal, Connective Tissue, and Bone Disorders Arthralgia, cramps, myositis, osteoporosis. Nervous System Disorders Paresthesia, restlessness.

Psychiatric Disorders Agitation, aggression, depression. Behavioral changes, including hyperactivity and irritability, have been reported very rarely and primarily in children. Reproductive System and Breast Disorders Dysmenorrhea. Respiratory, Thoracic, and Mediastinal Disorders Chest congestion; chest tightness; dyspnea; facial and oropharyngeal edema, immediate bronchospasm; paradoxical bronchospasm; tracheitis; wheezing; reports of upper respiratory symptoms of laryngeal spasm, irritation, or swelling such as stridor or choking.

Skin and Subcutaneous Tissue Disorders Ecchymoses, photodermatitis. Vascular Disorders Pallor.

15 ) Be alert to eosinophilic conditions, hypokalemia, and hyperglycemia. 18 ) Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis. 1 Serious Asthma-Related Events – Hospitalizations, Intubations, Death Use of LABA as monotherapy (without ICS) for asthma is associated with an increased risk of asthma-related death [see Salmeterol Multicenter Asthma Research Trial (SMART)] .

Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA monotherapy.

When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma‑related events (hospitalizations, intubations, death) compared with ICS alone (see Serious Asthma-Related Events with Inhaled Corticosteroid/Long-acting Beta 2 -adrenergic Agonists) .

Serious Asthma-Related Events with Inhaled Corticosteroid/Long-acting Beta 2 -adrenergic Agonists Four (4) large, 26-week, randomized, double-blind, active-controlled clinical safety trials were conducted to evaluate the risk of serious asthma-related events when LABA were used in fixed-dose combination with ICS compared with ICS alone in subjects with asthma.

1 )] , 1 trial compared mometasone furoate/formoterol with mometasone furoate, and 1 trial compared budesonide/formoterol with budesonide. 1 )] . The primary safety endpoint for all 4 trials was serious asthma-related events (hospitalizations, intubations, death).

A blinded adjudication committee determined whether events were asthma related. 7. Each individual trial met its pre-specified objective and demonstrated non-inferiority of ICS/LABA to ICS alone. A meta-analysis of the 3 adult and adolescent trials did not show a significant increase in risk of a serious asthma-related event with ICS/LABA fixed-dose combination compared with ICS alone ( Table 1 ).

These trials were not designed to rule out all risk for serious asthma-related events with ICS/LABA compared with ICS. Table 1. Meta-analysis of Serious Asthma-Related Events in Subjects with Asthma Aged 12 Years and Older ICS = Inhaled Corticosteroid, LABA = Long-acting Beta2-adrenergic Agonist.

a Randomized subjects who had taken at least 1 dose of study drug. Planned treatment used for analysis. b Estimated using a Cox proportional hazards model for time to first event with baseline hazards stratified by each of the 3 trials.

c Number of subjects with event that occurred within 6 months after the first use of study drug or 7 days after the last date of study drug, whichever date was later. Subjects can have one or more events, but only the first event was counted for analysis.

A single, blinded, independent adjudication committee determined whether events were asthma related. ICS/LABA (n = 17,537) a ICS (n = 17,552) a ICS/LABA vs. 44) Asthma-related death 2 0 Asthma-related intubation (endotracheal) 1 2 Asthma-related hospitalization (≥24-hour stay) 115 105 The pediatric safety trial included 6,208 pediatric subjects aged 4 to 11 years who received ICS/LABA (fluticasone propionate/salmeterol inhalation powder) or ICS (fluticasone propionate inhalation powder).

7%) subjects randomized to ICS experienced a serious asthma-related event. There were no asthma-related deaths or intubations. 27). S. 34]). Use of background ICS was not required in SMART. The increased risk of asthma-related death is considered a class effect of LABA monotherapy.

2 Deterioration of Disease and Acute Episodes Fluticasone Propionate/Salmeterol DISKUS should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of asthma or COPD. Fluticasone Propionate/Salmeterol DISKUS has not been studied in subjects with acutely deteriorating asthma or COPD.

The initiation of Fluticasone Propionate/Salmeterol DISKUS in this setting is not appropriate. Serious acute respiratory events, including fatalities, have been reported when salmeterol, a component of Fluticasone Propionate/Salmeterol DISKUS, has been initiated in patients with significantly worsening or acutely deteriorating asthma.

, patients with significantly increasing symptoms; increasing need for inhaled, short‑acting beta 2 -agonists; decreasing response to usual medications; increasing need for systemic corticosteroids; recent emergency room visits; deteriorating lung function).

However, these events have occurred in a few patients with less severe asthma as well. It was not possible from these reports to determine whether salmeterol contributed to these events. Increasing use of inhaled, short-acting beta 2 -agonists is a marker of deteriorating asthma.

In this situation, the patient requires immediate reevaluation with reassessment of the treatment regimen, giving special consideration to the possible need for replacing the current strength of Fluticasone Propionate/Salmeterol DISKUS with a higher strength, adding additional ICS, or initiating systemic corticosteroids.

Patients should not use more than 1 inhalation twice daily of Fluticasone Propionate/Salmeterol DISKUS. , as rescue therapy for the treatment of acute episodes of bronchospasm. Fluticasone Propionate/Salmeterol DISKUS has not been studied in the relief of acute symptoms and extra doses should not be used for that purpose.

Acute symptoms should be treated with an inhaled, short-acting beta 2 -agonist. , 4 times a day) should be instructed to discontinue the regular use of these drugs. 3 Excessive Use of Fluticasone Propionate/Salmeterol DISKUS and Use with Other Long-acting Beta 2 -agonists Fluticasone Propionate/Salmeterol DISKUS should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medicines containing LABA, as an overdose may result.

Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. , salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason.

4 Local Effects of Inhaled Corticosteroids In clinical trials, the development of localized infections of the mouth and pharynx with Candida albicans has occurred in subjects treated with fluticasone propionate/salmeterol DISKUS. , oral) antifungal therapy while treatment with Fluticasone Propionate/Salmeterol DISKUS continues, but at times therapy with Fluticasone Propionate/Salmeterol DISKUS may need to be interrupted.

Advise the patient to rinse his/her mouth with water without swallowing following inhalation to help reduce the risk of oropharyngeal candidiasis. 5 Pneumonia Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of pneumonia and exacerbations frequently overlap.

Lower respiratory tract infections, including pneumonia, have been reported in patients with COPD following the inhaled administration of corticosteroids, including fluticasone propionate and fluticasone propionate/salmeterol DISKUS.

In 2 replicate 1-year trials in 1,579 subjects with COPD, there was a higher incidence of pneumonia reported in subjects receiving fluticasone propionate/salmeterol DISKUS 250/50 mcg (7%) than in those receiving salmeterol 50 mcg (3%).

The incidence of pneumonia in the subjects treated with fluticasone propionate/salmeterol DISKUS was higher in subjects older than 65 years (9%) compared with the incidence in subjects younger than 65 years (4%). ] In a 3-year trial in 6,184 subjects with COPD, there was a higher incidence of pneumonia reported in subjects receiving fluticasone propionate/salmeterol DISKUS 500/50 mcg compared with placebo (16% with fluticasone propionate/salmeterol DISKUS 500/50 mcg, 14% with fluticasone propionate 500 mcg, 11% with salmeterol 50 mcg, and 9% with placebo).

Similar to what was seen in the 1-year trials with fluticasone propionate/salmeterol DISKUS 250/50 mcg, the incidence of pneumonia was higher in subjects older than 65 years (18% with fluticasone propionate/salmeterol DISKUS 500/50 mcg versus 10% with placebo) compared with subjects younger than 65 years (14% with fluticasone propionate/salmeterol DISKUS 500/50 mcg versus 8% with placebo).

6 Immunosuppression Persons who are using drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids.

In such children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known.

The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If a patient is exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If a patient is exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated.

) If chickenpox develops, treatment with antiviral agents may be considered. ICS should be used with caution, if at all, in patients with active or quiescent tuberculosis infections of the respiratory tract; systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.

7 Transferring Patients from Systemic Corticosteroid Therapy Particular care is needed for patients who have been transferred from systemically active corticosteroids to ICS because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available ICS.

After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function. Patients who have been previously maintained on 20 mg or more of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn.

During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss.

Although Fluticasone Propionate/Salmeterol DISKUS may control asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of glucocorticoid systemically and does NOT provide the mineralocorticoid activity that is necessary for coping with these emergencies.

During periods of stress or a severe asthma attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for further instruction.

These patients should also be instructed to carry a warning card indicating that they may need supplementary systemic corticosteroids during periods of stress or a severe asthma attack. Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to Fluticasone Propionate/Salmeterol DISKUS.

5 mg on a weekly basis during therapy with Fluticasone Propionate/Salmeterol DISKUS. Lung function (mean forced expiratory volume in 1 second [FEV 1 ] or morning peak expiratory flow [AM PEF]), beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of oral corticosteroids.

In addition, patients should be observed for signs and symptoms of adrenal insufficiency, such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension. , rhinitis, conjunctivitis, eczema, arthritis, eosinophilic conditions).

, joint and/or muscular pain, lassitude, depression) despite maintenance or even improvement of respiratory function. 8 Hypercorticism and Adrenal Suppression Fluticasone propionate, a component of Fluticasone Propionate/Salmeterol DISKUS, will often help control asthma symptoms with less suppression of HPA function than therapeutically equivalent oral doses of prednisone.

Since fluticasone propionate is absorbed into the circulation and can be systemically active at higher doses, the beneficial effects of Fluticasone Propionate/Salmeterol DISKUS in minimizing HPA dysfunction may be expected only when recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose.

A relationship between plasma levels of fluticasone propionate and inhibitory effects on stimulated cortisol production has been shown after 4 weeks of treatment with fluticasone propionate inhalation aerosol. Since individual sensitivity to effects on cortisol production exists, physicians should consider this information when prescribing Fluticasone Propionate/Salmeterol DISKUS.

Because of the possibility of significant systemic absorption of ICS in sensitive patients, patients treated with Fluticasone Propionate/Salmeterol DISKUS should be observed carefully for any evidence of systemic corticosteroid effects.

Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response. It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis) may appear in a small number of patients who are sensitive to these effects.

If such effects occur, Fluticasone Propionate/Salmeterol DISKUS should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids, and other treatments for management of asthma symptoms should be considered.

3 )] . 10 Paradoxical Bronchospasm and Upper Airway Symptoms As with other inhaled medicines, Fluticasone Propionate/Salmeterol DISKUS can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with Fluticasone Propionate/Salmeterol DISKUS, it should be treated immediately with an inhaled, short-acting bronchodilator; Fluticasone Propionate/Salmeterol DISKUS should be discontinued immediately; and alternative therapy should be instituted.

Upper airway symptoms of laryngeal spasm, irritation, or swelling, such as stridor and choking, have been reported in patients receiving fluticasone propionate/salmeterol DISKUS. , urticaria, angioedema, rash, bronchospasm, hypotension), including anaphylaxis, may occur after administration of Fluticasone Propionate/Salmeterol DISKUS.

There have been reports of anaphylactic reactions in patients with severe milk protein allergy after inhalation of powder products containing lactose; therefore, patients with severe milk protein allergy should not use Fluticasone Propionate/Salmeterol DISKUS [see Contraindications ( 4 )] .

2 )] . Therefore, Fluticasone Propionate/Salmeterol DISKUS, like all products containing sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Salmeterol, a component of Fluticasone Propionate/Salmeterol DISKUS, can produce a clinically significant cardiovascular effect in some patients as measured by pulse rate, blood pressure, and/or symptoms. Although such effects are uncommon after administration of salmeterol at recommended doses, if they occur, the drug may need to be discontinued.

In addition, beta-agonists have been reported to produce electrocardiogram (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.

Large doses of inhaled or oral salmeterol (12 to 20 times the recommended dose) have been associated with clinically significant prolongation of the QTc interval, which has the potential for producing ventricular arrhythmias. Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs.

13 Reduction in Bone Mineral Density Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing ICS. The clinical significance of small changes in BMD with regard to long-term consequences such as fracture is unknown.

, anticonvulsants, oral corticosteroids), should be monitored and treated with established standards of care. Since patients with COPD often have multiple risk factors for reduced BMD, assessment of BMD is recommended prior to initiating Fluticasone Propionate/Salmeterol DISKUS and periodically thereafter.

If significant reductions in BMD are seen and Fluticasone Propionate/Salmeterol DISKUS is still considered medically important for that patient’s COPD therapy, use of medicine to treat or prevent osteoporosis should be strongly considered.

2-Year Fluticasone Propionate Trial A 2-year trial in 160 subjects (females aged 18 to 40 years, males 18 to 50) with asthma receiving chlorofluorocarbon (CFC)-propelled fluticasone propionate inhalation aerosol 88 or 440 mcg twice daily demonstrated no statistically significant changes in BMD at any time point (24, 52, 76, and 104 weeks of double-blind treatment) as assessed by dual-energy x-ray absorptiometry at lumbar regions L1 through L4.

3-Year Bone Mineral Density Trial Effects of treatment with fluticasone propionate/salmeterol DISKUS 250/50 mcg or salmeterol 50 mcg on BMD at the L 1 -L 4 lumbar spine and total hip were evaluated in 186 subjects with COPD (aged 43 to 87 years) in a 3-year double-blind trial.

Of those enrolled, 108 subjects (72 males and 36 females) were followed for the entire 3 years. BMD evaluations were conducted at baseline and at 6-month intervals. Conclusions cannot be drawn from this trial regarding BMD decline in subjects treated with fluticasone propionate/salmeterol DISKUS versus salmeterol due to the inconsistency of treatment differences across gender and between lumbar spine and total hip.

In this trial there were 7 non-traumatic fractures reported in 5 subjects treated with fluticasone propionate/salmeterol DISKUS and 1 non-traumatic fracture in 1 subject treated with salmeterol. None of the non-traumatic fractures occurred in the vertebrae, hip, or long bones.

3-Year Survival Trial Effects of treatment with fluticasone propionate/salmeterol DISKUS 500/50 mcg, fluticasone propionate 500 mcg, salmeterol 50 mcg, or placebo on BMD was evaluated in a subset of 658 subjects (females and males aged 40 to 80 years) with COPD in the 3-year survival trial.

BMD evaluations were conducted at baseline and at 48, 108, and 158 weeks. Conclusions cannot be drawn from this trial because of the large number of dropouts (>50%) before the end of the follow-up and the maldistribution of covariates among the treatment groups that can affect BMD.

Fracture risk was estimated for the entire population of subjects with COPD in the survival trial (N = 6,184). 1% for placebo. 14 Effect on Growth Orally inhaled corticosteroids may cause a reduction in growth velocity when administered to pediatric patients.

, via stadiometry). 4 )] . 15 Glaucoma and Cataracts Glaucoma, increased intraocular pressure, and cataracts have been reported in patients with asthma and COPD following the long-term administration of ICS, including fluticasone propionate, a component of Fluticasone Propionate/Salmeterol DISKUS.

Consider referral to an ophthalmologist in patients who develop ocular symptoms or use Fluticasone Propionate/Salmeterol DISKUS long term. Effects of treatment with fluticasone propionate/salmeterol DISKUS 500/50 mcg, fluticasone propionate 500 mcg, salmeterol 50 mcg, or placebo on development of cataracts or glaucoma was evaluated in a subset of 658 subjects with COPD in the 3-year survival trial.

Ophthalmic examinations were conducted at baseline and at 48, 108, and 158 weeks. Conclusions about cataracts cannot be drawn from this trial because the high incidence of cataracts at baseline (61% to 71%) resulted in an inadequate number of subjects treated with fluticasone propionate/salmeterol DISKUS 500/50 mcg, who were eligible and available for evaluation of cataracts at the end of the trial (n = 53).

The incidence of newly diagnosed glaucoma was 2% with fluticasone propionate/salmeterol DISKUS 500/50 mcg, 5% with fluticasone propionate, 0% with salmeterol, and 2% with placebo. 16 Eosinophilic Conditions and Churg-Strauss Syndrome In rare cases, patients on inhaled fluticasone propionate, a component of Fluticasone Propionate/Salmeterol DISKUS, may present with systemic eosinophilic conditions.

Some of these patients have clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition that is often treated with systemic corticosteroid therapy. These events usually, but not always, have been associated with the reduction and/or withdrawal of oral corticosteroid therapy following the introduction of fluticasone propionate.

Cases of serious eosinophilic conditions have also been reported with other ICS in this clinical setting. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients.

A causal relationship between fluticasone propionate and these underlying conditions has not been established. 17 Coexisting Conditions Fluticasone Propionate/Salmeterol DISKUS, like all medicines containing sympathomimetic amines, should be used with caution in patients with convulsive disorders or thyrotoxicosis and in those who are unusually responsive to sympathomimetic amines.

Doses of the related beta 2 -adrenoceptor agonist albuterol, when administered intravenously, have been reported to aggravate preexisting diabetes mellitus and ketoacidosis. 2 )] . The decrease in serum potassium is usually transient, not requiring supplementation.

Clinically significant changes in blood glucose and/or serum potassium were seen infrequently during clinical trials with fluticasone propionate/salmeterol DISKUS at recommended doses.